.I 200405 .U 90000002 .S Alcohol Alcohol 9001; 24(4):281-9 .M Acetaldehyde/*ME; Animal; Cell Survival; Cytoskeleton/ME; Liver/CY/ME; Microfilament Proteins/*ME; Muscles/CY/ME; Rabbits; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Covalent interactions of acetaldehyde with the actin/microfilament system. .P JOURNAL ARTICLE. .W The covalent binding of [14C]acetaldehyde to purified rabbit skeletal muscle actin was characterized. As we have found for other cytoskeletal proteins, actin formed stable covalent adducts under reductive and non-reductive conditions. Under non-reductive conditions, individual and competition binding studies versus albumin both showed that the G-form of actin is more reactive toward acetaldehyde than the F-form. When proteins were compared on an 'equi-lysine' basis under non-reducing conditions, G-actin was found to preferentially compete with albumin for binding to acetaldehyde. Time-course dialysis studies indicated that acetaldehyde-actin adducts become more stable with prolonged incubation at 37 degrees C. These data raise the possibility that actin could be a preferential target for adduct formation in cellular systems and will serve as the basis for ongoing studies aimed at defining the role of acetaldehyde-protein adducts in ethanol-induced cell injury. .A Xu DS; Jennett RB; Smith SL; Sorrell MF; Tuma DJ. .I 200406 .U 90000005 .S Alcohol Alcohol 9001; 24(4):311-8 .M Alcohol, Ethyl/*AD; Animal; Comparative Study; DNA/AN; Liver/*ME/UL; Male; Phenylalanine; Proteins/*BI; Rats; Rats, Inbred Strains; RNA/AN. .T An investigation into the effects of chronic ethanol feeding on hepatic mixed protein synthesis in immature and mature rats. .P JOURNAL ARTICLE. .W 1. The response of the liver to chronic ethanol feeding was investigated in sexually immature (85 g) and sexually mature (280 g) male Wistar rats. Rats received a nutritionally adequate liquid diet ad libitum, in which ethanol comprised 36% of total calories, for up to 6 weeks. Controls were pair-fed the same liquid diet in which ethanol was substituted by isocaloric glucose. 2. In immature rats, total hepatic protein, RNA and DNA contents were reduced by 12-23%. The amount of RNA, relative to protein or DNA, was also decreased by 11-12%, though the amount of protein relative to DNA was unaltered. In mature rats, no change in total hepatic protein and DNA contents were observed, though total RNA, RNA/protein ratio, RNA/DNA ratio and the amount of protein relative to DNA was reduced by 7-18%. 3. Rates of protein synthesis were measured with a flooding dose of L[4-3H]-phenylalanine without anaesthesia or surgical stress. In both immature and mature rats the fractional and absolute rates of hepatic protein synthesis and protein synthesis relative to DNA were reduced by approx 25%. .A Preedy VR; Peters TJ. .I 200407 .U 90000007 .S Alcohol Alcohol 9001; 24(4):331-7 .M Adolescence; Adult; Aged; Alcoholism/*PX; Comparative Study; Female; Human; Liver Diseases, Alcoholic/PX; Marriage/*; Middle Age; Personal Satisfaction/*; Role; Socioeconomic Factors; Support, Non-U.S. Gov't; Women/*PX. .T Alcoholic housewives and role satisfaction. .P JOURNAL ARTICLE. .W Three groups of housewives adhering to strict inclusion criteria were compared along several variables. The groups were patients with non-alcoholic liver disease (N = 19), alcoholic liver disease (N = 15) and alcoholics attending a community treatment centre (N = 13). The study confirms the differences between alcoholics who develop liver disease from those who do not. There was a strong relationship between dissatisfaction with the role of housewife and severity of alcoholism. .A Farid B; Elsherbini M; Ogden M; Lucas G; Williams R. .I 200408 .U 90000008 .S Alcohol Alcohol 9001; 24(4):339-45 .M Alcoholism/*PC; Curriculum/*; Education, Medical/*; England; Health Behavior; Human; Interpersonal Relations; Male; Physicians/*; Smoking/*. .T The medical profession has achieved a major change in its smoking behaviour; how might undergraduate medical education achieve a similar change in doctors' drinking habits? .P JOURNAL ARTICLE. .A Talbot K. .I 200409 .U 90000010 .S Alcohol Alcohol 9001; 24(4):355-7 .M Alcohol Drinking/*; Female; Human; Pregnancy/*PH; Risk Factors; Smoking. .T Comments on a paper by M. L. Plant and M. A. Plant [letter; comment] .P COMMENT; LETTER. .A Murray-Lyon I; Waterson J. .I 200410 .U 90000152 .S Acad Med 9001; 64(10):574-5 .M Career Choice/*; Curriculum; Education, Medical, Undergraduate; Human; New Hampshire; Physician's Role/*; Role/*; Students, Medical/*; Vocational Guidance/*. .T Effective use of medical school alumni to improve career counseling for students. .P JOURNAL ARTICLE. .A Regan-Smith M; Eisold J; Boulter S; Stebbins P. .I 200411 .U 90000153 .S Acad Med 9001; 64(10):575-8 .M California; Curriculum; Education, Graduate/*; Human; Medical Informatics/*ED; Philosophy; Research/*; Students; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Research training in medical informatics: the Stanford experience. .P JOURNAL ARTICLE. .A Shortliffe EH; Fagan LM. .I 200412 .U 90000154 .S Acad Med 9001; 64(10):580 .M Health Services Accessibility/*LJ; Human; United States. .T Health care for all: the building crisis. .P JOURNAL ARTICLE. .A Rockefeller JD 4th. .I 200413 .U 90000156 .S Acad Med 9001; 64(10):583 .M Career Choice/*; Human; Specialties, Medical/*; Students, Medical/*; United States. .T Specialty choice. .P JOURNAL ARTICLE. .A Swanson AG. .I 200414 .U 90000157 .S Acad Med 9001; 64(10):584 .M Cognition Disorders/*ET; Human; Internship and Residency/*; Sleep Deprivation/*; Work/*; Work Schedule Tolerance/*. .T Swingshift encephalopathy [comment] .P COMMENT; JOURNAL ARTICLE. .A Wagner M. .I 200415 .U 90000158 .S Acad Med 9001; 64(10):586-7 .M Education, Medical, Undergraduate/*; Human; Nutrition/*ED; United States. .T Medical nutrition education [letter; comment] .P COMMENT; LETTER. .A Weinsier RL; Brooks CM. .I 200416 .U 90000159 .S Acad Med 9001; 64(10):588-94 .M Acquired Immunodeficiency Syndrome/*PX; Career Choice/*; Comparative Study; Human; Internship and Residency/*SN; Professional Practice Location; Specialties, Medical/*/ED/MA; Students, Medical/*PX; Support, Non-U.S. Gov't; United States; Urban Population. .T Likelihood of contact with AIDS patients as a factor in medical students' residency selections. .P JOURNAL ARTICLE. .W Results from the National Resident Matching Program for the years 1980, 1983, and 1987 were used to examine changes over time in the matches of U.S. medical students to residencies in cities with high concentrations of patients with acquired immunodeficiency syndrome (AIDS) and to specialties in which the care of AIDS patients was most concentrated. Medical students seeking postgraduate training in categorical surgery residency programs were less likely to be matched with programs located in areas where the numbers of reported AIDS cases were high in 1987 as compared with the "pre-AIDS" years of 1980 or 1983. This trend was more pronounced for students from medical schools located in cities with high numbers of AIDS cases. There was a decline in matches to residencies in categorical internal medicine nationally, regardless of location; this decline was also greater among the students coming from medical schools in cities with high numbers of AIDS cases. The authors discuss the implications for medical educators of declines in matches to specialties in which the care of AIDS patients is most concentrated. The imperfect nature of available measures of students' exposure to AIDS patients makes the data of this study preliminary, and further studies are being undertaken. However, the finding of significant effects in spite of the imprecision of some measures suggests that future work will confirm the results of this study. .A Ness R; Killian CD; Ness DE; Frost JB; McMahon D. .I 200417 .U 90000160 .S Acad Med 9001; 64(10):595-9 .M Career Choice/*; Comparative Study; Ethnic Groups/*SN; Female; Human; Internship and Residency/*SN; Male; Minority Groups/SN; Questionnaires; Sex Factors; Specialties, Medical/*/ED/MA; Students, Medical/*SN; Students, Premedical/SN; Support, Non-U.S. Gov't; United States. .T Racial-ethnic background and specialty choice: a study of U.S. medical school graduates in 1987. .P JOURNAL ARTICLE. .W This study used two Association of American Medical Colleges' questionnaires to determine whether there was a relationship between the racial-ethnic backgrounds and the specialty choices of a 1987 cohort of 11,136 U.S. medical school seniors, both prior to entering medical school and as they prepared for residency training. Their specialty preferences as premedical students were shown by their responses to the Premedical Student Questionnaire, administered when they registered for the Medical College Admission Test; their specialty choices at the end of their medical school training were shown by their responses to the Medical Student Graduation Questionnaire, which they completed shortly before graduation. Racial-ethnic backgrounds, self-recorded, were classified into black, other underrepresented minorities, Asian, other non-underrepresented minorities, and white. Specialties were clustered into primary care, medical specialties, surgical specialties, and supporting services. Before entering medical school, the students had similar specialty preferences regardless of background. As seniors in medical school, there was even greater convergence of specialty choices among the students of all backgrounds. Racial-ethnic background in itself appears not to have been a major factor influencing the senior medical students' specialty choices. .A Babbott D; Baldwin DC Jr; Killian CD; Weaver SO. .I 200418 .U 90000161 .S Acad Med 9001; 64(10):600-5 .M Career Choice/*; Choice Behavior; Comparative Study; Female; Human; Male; Pediatrics/*/ED/MA; Primary Health Care; Sex Factors; Specialties, Medical/ED/MA; Statistics; Students, Medical/*SN; Students, Premedical/*SN; Support, Non-U.S. Gov't; United States. .T Early and final preferences for pediatrics as a specialty: a study of U.S. medical school graduates in 1983. .P JOURNAL ARTICLE. .W The early and final specialty preferences for pediatrics made by 10,321 U.S. medical school graduates in 1983 were obtained from the students' responses to the Premedical Student Questionnaire, which accompanied their Medical College Admissions Test, and to the Medical Student Graduation Questionnaire, filled out not long before they graduated from medical school. A total of 11.5% of the women and 5.9% of the men expressed a preference for pediatrics on the earlier questionnaire, when they were premedical students; 13.5% of the women and 4.8% of the men actually chose pediatrics when they were senior medical students, as reflected on the later questionnaire. On both questionnaires, 31.3% of the women's preferences and 14.6% of the men's preferences for pediatrics did not change. More than 70% of all the graduating students choosing pediatrics had expressed a premedical preference for a primary care specialty. Fifty-one percent of the women and 42% of the men who abandoned their early preferences for pediatrics chose another specialty within primary care. More students of both genders shifted from a premedical preference for family practice into pediatrics than kept their early preference for pediatrics. If the direction of change noted in this study and others continues, pediatrics will increasingly become a specialty chosen by women. .A Coffin SE; Babbott D. .I 200419 .U 90000162 .S Acad Med 9001; 64(10):606-9 .M Achievement; Career Choice/*; Educational Measurement; Human; Internship and Residency/SN; Kentucky; Life Style/*; Primary Health Care/MA; Specialties, Medical/*/ED/MA; Students, Medical/*SN; Virginia. .T Controllable lifestyle: a new factor in career choice by medical students. .P JOURNAL ARTICLE. .W To determine whether control of work hours (controllable lifestyle) was becoming an increasingly important factor in choices of specialties by medical students, data from three medical schools over the past ten, ten, and six years, respectively, were reviewed for the types of specialty training entered by students in the top 15% of their classes. Since students in the upper 15% of the class are likely to obtain the specialties of their choice, any change in the pattern of their specialty preferences probably reflects a general trend. Specialties that feature a controllable lifestyle (CL) were defined as anesthesiology, dermatology, emergency medicine, neurology, ophthalmology, otolaryngology, pathology, psychiatry, and radiology. Non-CL specialties were surgery, medicine, family practice, pediatrics, and obstetrics-gynecology. The results showed that the percentages of students entering CL specialties increased significantly at all three schools, the percentages of students entering non-CL specialties decreased significantly at all three schools, and there was no significant change in the percentage of students entering surgical specialties. .A Schwartz RW; Jarecky RK; Strodel WE; Haley JV; Young B; Griffen WO Jr. .I 200420 .U 90000163 .S Acad Med 9001; 64(10):610-5 .M Career Choice/*; Cross-Sectional Studies; Curriculum; Family Practice/*/ED/MA; Human; Internship and Residency/*SN; Ownership; Schools, Medical/*/CL; Time Factors; United States. .T Characteristics of medical schools related to the choice of family medicine as a specialty. .P JOURNAL ARTICLE. .W Previous research has identified five characteristics of medical schools that are related to the choice of family medicine as a specialty: (1) the amount of time devoted to required training in family medicine, (2) the timing of the required family medicine training, (3) the type of ownership of the school (public or private), (4) the geographic location of the school, and (5) the administrative structure of family medicine within the school. These five characteristics of U.S. medical schools during the mid-1980s, together with the school tuition levels, were examined with both univariate and multivariate analysis to observe their relationships to the percentage of U.S. medical graduates entering family medicine between July 1986 and December 1987. With univariate analysis, each characteristic was significantly related to the percentage of graduates entering family medicine. Using multivariate analysis, only the number of weeks required and the type of ownership of the school were significantly related to the percentage of graduates entering family medicine, with the higher percentages related to greater numbers of required weeks of family medicine training and to public ownership of the school. .A Campos-Outcalt D; Senf JH. .I 200421 .U 90000164 .S Acad Med 9001; 64(10):616-21 .M Achievement; Career Choice/*; Comparative Study; Education, Medical, Undergraduate; Educational Measurement; Female; Human; Male; Schools, Medical; Sex Factors; Specialties, Medical/*/ED/MA; Students, Medical/*SN; United States. .T Initial career choices of medical school honors graduates in the early 1970s and 1980s. .P JOURNAL ARTICLE. .W To investigate the changes over time in the attractiveness of a number of medical specialties as careers, the author analyzed the initial career pathways of students who graduated with honors in 1972, 1973, 1982, and 1983 from nine of the most prestigious American medical schools. The data were analyzed to discern career selection differences among the total population studied, between the men and women, and between the graduates of public and private institutions. Internal medicine showed statistically significant declines in its attractiveness to the students in all the categories but remained overrepresented as a career choice by honors students compared with its attractiveness to medical students in general for the years studied. Radiology was chosen by an increasing percentage of the honors students in the 1980s, but mostly by students from private medical schools. The men who were honors graduates in the 1980s chose surgery fields more often, while women honors graduates tended to enter pediatrics and obstetrics-gynecology. These data indicate that the career choices of honors graduates in the early 1980s more closely mirrored the career choices of all students entering medical specialty fields and do not reveal gross imbalances. Of the primary care disciplines, only internal medicine attracted fewer honors graduates in the 1980s. .A Golden WE. .I 200422 .U 90000165 .S Acad Med 9001; 64(10):622-9 .M Acquired Immunodeficiency Syndrome; Career Choice/*; Comparative Study; Female; Human; Internship and Residency; Male; Primary Health Care; San Francisco; Schools, Medical; Specialties, Medical/ED/*MA; Statistics; Students, Medical/*; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Technology. .T Specialty choices at one medical school: recent trends and analysis of predictive factors. .P JOURNAL ARTICLE. .W Recent reports have raised the concern that personal care specialties, especially primary care specialties, are attracting fewer medical school graduates. In the present study, the authors evaluated the proportions of University of California, San Francisco (UCSF), medical school graduates entering personal care specialties and technology-oriented specialties from 1982 through 1988 and found no significant trend away from personal care specialties such as internal medicine, family practice, pediatrics, and psychiatry during these years. For the graduating class of 1988, admissions and questionnaire data were used to evaluate the importance of pre-admission, medical school, and postgraduate factors as determinants of specialty choice. The group entering personal care specialties (66% of all 1988 graduates) was significantly older and included more women and fewer minority students than the group entering technology-oriented specialties. Students rated income and lifestyle factors as being less important determinants of specialty choice than are medical school experiences and intrinsic qualities of the chosen specialties. However, compared with the students who entered personal care specialties, those who chose technology-oriented specialties over an alternate choice in personal care rated as significantly more important the opportunity to do procedures (p less than .001), income (p less than .005), the lesser degree of diagnostic uncertainty (p less than .005), and the rejected specialty's allowing less time for family (p less than .005) and for other interests (p less than .008). Exposure to acquired immunodeficiency syndrome and loan indebtedness were rated the least significant influences on specialty choice.(ABSTRACT TRUNCATED AT 250 WORDS) .A Lieu TA; Schroeder SA; Altman DF. .I 200423 .U 90000166 .S Acad Med 9001; 64(10):630-3 .M Ethnic Groups/SN; Female; Human; Internship and Residency/*SN; Male; Minority Groups/SN; Sex Factors; Specialties, Medical/ED/MA/*SN; United States. .T Present activities of 1989 U.S. medical graduates. .P JOURNAL ARTICLE. .A Swanson, AG; Randlett RR; Haynes RA; Killian CD. .I 200424 .U 90000167 .S Acad Med 9001; 64(10 Suppl):S1-4 .M Ambulatory Care/*SN; Curriculum; Education, Medical/*SN; Education, Medical, Undergraduate/SN; Hospitals, Veterans/*; Human; Internship and Residency; Questionnaires; Schools, Medical/*; Specialties, Medical/ED; United States. .T A study of ambulatory care education in medical schools and U.S. Department of Veterans Affairs health care facilities. .P JOURNAL ARTICLE. .W A study of ambulatory care and education was conducted by sending questionnaires to U.S. Department of Veterans Affairs hospitals (75) and medical schools (65) prior to the Conference on Ambulatory Care and Education. Responses from 48% of medical schools indicated that there was little required clinical time in ambulatory care (15-20%), as well as faculty resistance and lack of medical school commitment to ambulatory care education. VA respondents (35% sample) also documented relatively little training in ambulatory care at the undergraduate and graduate levels. Numerous barriers to ambulatory care education are mentioned and strategies for overcoming the problems found are discussed. .A Robbins AS; Lussier RR; Koser K. .I 200425 .U 90000168 .S Acad Med 9001; 64(10 Suppl):S1-74 .M Ambulatory Care/*; Education, Medical/*; Human; United States. .T Proceedings from the Conference on Ambulatory Care and Education. July 1988, Los Angeles, California. .P JOURNAL ARTICLE. .I 200426 .U 90000169 .S Acad Med 9001; 64(10 Suppl):S16-21 .M Ambulatory Care/*; Clinical Competence; Curriculum; Faculty, Medical; Fellowships and Scholarships; Hospitals, Veterans/*; Human; Internship and Residency/*TD; United States. .T Graduate medical education in ambulatory care. .P JOURNAL ARTICLE. .W Graduate medical education is currently in transition, with educators being asked to re-examine the extent to which hospital-based teaching models still provide adequate comprehensive training. To educate future physicians adequately, the Department of Veterans Affairs (VA) will have to change its system for delivering ambulatory care services and for teaching in ambulatory care settings. Workshop discussions focused on five major areas regarding educating residents in the ambulatory setting: educational goals and objectives, clinical experiences, curriculum development and evaluation, faculty issues, and fellowship opportunities. Recommendations include the need for residency programs to develop explicit educational goals and objectives for resident training, the identification of transdepartmental needs and coordinated planning, the support of academic clinical faculty, research and development of educational programs, and further development of fellowship training in ambulatory care. Further integration of ambulatory care activities in graduate training will require significant effort, a shift in manpower and resources and, more fundamentally, a shift in attitude and commitment at all levels of the VA and medical schools. .A Hayashi SA; Hayden BB; Yager J; Guze PA. .I 200427 .U 90000171 .S Acad Med 9001; 64(10 Suppl):S28-34 .M Ambulatory Care/*OG; Hospital Design and Construction; Hospitals, Veterans/*OG; Human; Leadership; Management Information Systems; Personnel Management; Quality Assurance, Health Care; United States. .T Administration in ambulatory care. .P JOURNAL ARTICLE. .W Deficiencies in management of U.S. Department of Veterans Affairs (USDVA) ambulatory care programs have been documented in the literature and were reaffirmed by conference participants. These represent significant barriers to developing an effective and efficient system of outpatient health care delivery for veterans and to expanding educational opportunities for trainees. Based on impact and feasibility rankings from the symposium, review of the literature, and the personal experiences of USDVA ambulatory care managers, several recommendations emerged: (1) implement a system of matrix management; (2) invest in a leader; (3) develop "user-friendly" management information systems; (4) utilize existing resources efficiently; (5) embrace quality assurance; and (6) improve support from clerical and diagnostic services, nursing, and pharmacy personnel. Although intervention from leadership at the level of the USDVA Central Office will be necessary, many of these recommendations can be adopted by managers at the local facilities. The biggest challenge is to change the attitudes of clinical and support staff whose responsibilities have traditionally been inpatient-oriented. .A Nardone DA; Webb DW. .I 200428 .U 90000172 .S Acad Med 9001; 64(10 Suppl):S35-43 .M Ambulatory Care/*; Ambulatory Care Information Systems; Faculty, Medical; Forecasting; Health Services Research/*; Hospitals, Veterans/*OG; Human; Research Personnel; Research Support; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; United States. .T Ambulatory care research in the VA: present status and recommendations for the future. .P JOURNAL ARTICLE. .W The growth of ambulatory care delivery in the Department of Veterans Affairs (VA) has been accompanied by increasing interest in and need for ambulatory care research. Results from a national survey of academic general internal medicine units suggest that those that share VA and university affiliation tend to be more successful than those that are unaffiliated. The VA must strive to improve the environment for ambulatory care research. Among other things, this will entail providing adequate protected time to ambulatory care faculty and developing a uniform ambulatory care database to facilitate longitudinal, population-based research. Extended fellowships in ambulatory care and faculty development programs for existing staff will be required to create a core of competent investigators. The VA must also provide increased funding to the Health Services Research and Development and Cooperative Studies programs. Special funding programs targeted to key areas such as quality assurance, medical education, and direct patient care should be established. In addition, the VA should seek to develop joint ventures with other funding agencies for innovative ambulatory care initiatives. .A Fihn SD; Larson EB; Friedman RH; Moskowitz MA. .I 200429 .U 90000174 .S Acad Med 9001; 64(10 Suppl):S44-50 .M Ambulatory Care/*EC; Capitation Fee; Costs and Cost Analysis; Education, Medical/*EC; Hospitals, Veterans/*EC; Human; Office Visits/EC; Outpatients/CL; Reimbursement Mechanisms; United States. .T Costs associated with ambulatory care and education. .P JOURNAL ARTICLE. .W The adoption of an ambulatory care classification system by the Health Care Financing Administration in 1991 may have significant implications for medical education programs in the Department of Veterans Affairs (VA) ambulatory care setting. Presently there is not adequate methodology in the VA to determine costs in ambulatory care and education. (Experience with the VA allocation model suggests that selected characteristics of reimbursement systems are incompatible with educational goals.) Barriers that inhibit the cost-effective delivery of ambulatory care in many VA hospitals must be eliminated so that effective patient care and training care can take place. These barriers include inadequacies of information systems, physical layouts, and staffing. Despite the perception that outpatient care is less costly than inpatient care, the transition from an inpatient-based education model to an ambulatory care model will require an infusion of resources to improve the ambulatory care environment in the VA. .A Lee D; Nugent G. .I 200430 .U 90000175 .S Acad Med 9001; 64(10 Suppl):S53-5 .M Ambulatory Care/*OG; Education, Medical/*/OG; Fellowships and Scholarships; Hospitals, Veterans/*OG; Human; Internship and Residency/*OG; Schools, Medical/OG; United States. .T Undergraduate and graduate medical education in ambulatory care. .P JOURNAL ARTICLE. .I 200431 .U 90000177 .S Acad Med 9001; 64(10 Suppl):S59-63 .M Ambulatory Care/*OG; Hospitals, Veterans/*OG; Human; Quality Assurance, Health Care; United States. .T Ambulatory care management. .P JOURNAL ARTICLE. .I 200432 .U 90000178 .S Acad Med 9001; 64(10 Suppl):S63 .M Ambulatory Care Information Systems/*; Hospitals, Veterans/*; Information Systems/*; United States. .T Ambulatory care database. .P JOURNAL ARTICLE. .I 200433 .U 90000179 .S Acad Med 9001; 64(10 Suppl):S64-7 .M Ambulatory Care/*EC; Hospital Design and Construction; Hospitals, Veterans/*EC; Reimbursement Mechanisms/*; United States. .T Ambulatory care resources and reimbursement systems. .P JOURNAL ARTICLE. .I 200434 .U 90000180 .S Acad Med 9001; 64(10 Suppl):S9-15 .M Ambulatory Care/*; Education, Medical, Undergraduate/*/EC; Faculty, Medical; Hospitals, Veterans; Human; Organizational Objectives; Schools, Medical; Students, Medical; United States. .T Medical student education in ambulatory care. .P JOURNAL ARTICLE. .W New forms of health care delivery and reimbursement trends have increased interest in the ambulatory care setting as a site for medical student education. It is estimated that from 50% to 60% of all medical students receive some portion of their medical training in a Department of Veterans Affairs (VA) facility. However, only about 5% of the total student ambulatory care educational experience is taking place at VA facilities. The problems in implementing and maintaining ambulatory care teaching programs for medical students encompass a variety of areas, such as lack of faculty incentive, time, expertise, and commitment; student resistance to training in this less attractive arena, and economic obstacles. Medical schools and VA medical centers will have to work in a mutually supportive relationship to develop joint goals and objectives for medical student teaching. Commitment of resources is essential, as is the need to reward ambulatory teaching through academic advancement and salary incentives. Faculty recruitment and development will be necessary, and research to identify the most successful of the VA ambulatory care teaching settings should be undertaken. The time has come for improved medical student education in VA ambulatory care settings, and there is now a need for collaborative planning between the medical schools and the VA. .A Abbott AV; Lee PV. .I 200435 .U 90000774 .S Arch Otolaryngol Head Neck Surg 9001; 115(10):1168-9 .M Human; Rhinoplasty/*MT. .T The tripod concept [news] .P NEWS. .A Larrabee WF Jr. .I 200436 .U 90000775 .S Arch Otolaryngol Head Neck Surg 9001; 115(10):1181-5 .M Aged; Carcinoma, Squamous Cell/*SU; Female; Human; Male; Middle Age; Mouth/*SU; Mouth Neoplasms/*SU; Nasopharyngeal Neoplasms/*SU; Oropharynx/*SU; Postoperative Complications; Radical Neck Dissection; Surgical Flaps/*; Surgical Wound Dehiscence/ET. .T Lower trapezius myocutaneous island flap. .P JOURNAL ARTICLE. .W Resurfacing of the floor of the mouth and buccal region of the oral cavity and the tonsillar region of the oropharynx may be accomplished with many variations of regional and distant vascularized flaps. Our experiences in the use of 14 lower trapezius myocutaneous island flaps are described with respect to the unique application and suitability of this flap to resurface defects in these areas, as well as the contraindications, both relative and absolute, to the use of this particular method of resurfacing. In addition, the intraoperative technique and attendant problems, as well as postoperative complications, are presented. The overall advantages and disadvantages of this flap as compared with the more traditional pectoralis myocutaneous flap are outlined. It is our belief that because of the distinct qualities of this flap, including extended scope and flap thinness, this method of reconstruction merits consideration in the preoperative planning process. .A Cummings CW; Eisele DW; Coltrera MD. .I 200437 .U 90000776 .S Arch Otolaryngol Head Neck Surg 9001; 115(10):1186-9 .M Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell/MO/PA/*TH; Combined Modality Therapy; Female; Human; Male; Middle Age; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasms, Multiple Primary/TH; Postoperative Complications; Retrospective Studies; Tonsillar Neoplasms/MO/PA/*TH. .T Carcinoma of the tonsillar fossa. An update. .P JOURNAL ARTICLE. .W A retrospective analysis of 162 patients with carcinoma of the tonsillar fossa treated between 1969 and 1983 was undertaken. Of these patients, 117 were previously untreated; 11 had stage I, carcinoma, 24 had stage II, 40 had stage III, and 42 had stage IV. Combination therapy was utilized in 29% of patients with stage II disease, 40% of patients with stage III disease, and 67% of patients with stage IV disease. The three-year determinate "cure" rates were 89%, 83%, 58%, and 49% for stages I through IV, respectively. Only 22% of the previously treated patients were salvaged. Complications occurred in 36% of the previously treated patients and 18% of the previously untreated patients. Since our previous report, survival has improved, whereas operative mortality has decreased. We are unable to demonstrate a significant survival advantage when surgery and radiotherapy were used in combination. .A Spiro JD; Spiro RH. .I 200438 .U 90000777 .S Arch Otolaryngol Head Neck Surg 9001; 115(10):1190-2 .M Human; Mandible/*SU; Mandibular Neoplasms/SU; Postoperative Complications; Surgical Flaps/*. .T Nonrigid reconstruction of the mandible. .P JOURNAL ARTICLE. .W Immediate rigid reconstruction of sacrificed portions of the mandible is desirable, but experience has shown that as many as 50% of bony or alloplastic implants are ultimately rejected or removed within the first few months after reconstruction. Functional and cosmetic reconstruction of the mandible, floor of the mouth, and, where necessary, skin of the lower lip and chin can be achieved with various local and myocutaneous flaps, to be followed after approximately 1 year by secondary bony reconstruction with a significantly lower complication rate. We describe the results in 43 patients treated by this approach. .A Tucker HM. .I 200439 .U 90000778 .S Arch Otolaryngol Head Neck Surg 9001; 115(10):1193-6 .M Adult; Aged; Carcinoma, Squamous Cell/PA/RT/SC/*SU; Combined Modality Therapy; Female; Human; Laryngeal Neoplasms/PA/RT/*SU; Lymph Node Excision/*MT; Male; Middle Age; Neoplasm Recurrence, Local; Neoplasm Staging; Radical Neck Dissection; Retrospective Studies. .T Five-year results of functional neck dissection for cancer of the larynx. .P JOURNAL ARTICLE. .W Two hundred forty-two patients with a diagnosis of epidermoid carcinoma of the larynx were studied. All of them underwent surgery. One hundred sixty-one patients underwent functional neck dissection, with a total of 206 performed. Thirty-three patients underwent classic radical neck dissection, with a total of 35 performed. The overall 5-year neck tumor recurrence rate in the necks with functional neck dissection was 3.4%. Recurrences developed in 5.7% of fields protected by radical neck dissection. The overall recurrence rate in the surgically unprotected necks was 6.2%. Our results confirm that functional neck dissection is the procedure of choice in cases with NO disease and in cases with mobile nodes. From the oncologic viewpoint, functional neck dissection is a safe technique to treat the cervical spread from cancer of the larynx as long as its indications and technical characteristics are carefully observed. .A Gavilan C; Gavilan J. .I 200440 .U 90000780 .S Arch Otolaryngol Head Neck Surg 9001; 115(10):1203-5 .M Adolescence; Adult; Aged; Bandages; Epistaxis/*PC; Female; Gelatin Sponge, Absorbable; Hemostasis, Surgical/MT; Human; Male; Middle Age; Rhinoplasty/*MT. .T Alternatives to packing in septorhinoplasty. .P JOURNAL ARTICLE. .W Nasal packing is considered routine by most physicians and patients at the completion of nasal and septal surgery. Yet the rationale for this maneuver is not clearly defined by reported investigation or logical analysis. We discuss 75 consecutive nasal surgical procedures completed without packing. There were two postoperative episodes of bleeding, both from pyriform aperture incisions for lateral osteotomy and both managed in the recovery room with an absorbable gelatin sponge. Technical refinements such as scrupulous preoperative history taking, through-and-through suturing of the entire septal flaps, small-caliber osteotomy, meticulous closure of all intranasal incisions, and proper application of a conforming dressing are essential for hemostasis. We offer specific procedural guidance to minimize the risk of postoperative nasal bleeding. .A Reiter D; Alford E; Jabourian Z. .I 200441 .U 90000781 .S Arch Otolaryngol Head Neck Surg 9001; 115(10):1206-12 .M Follow-Up Studies; Human; Nasal Septum/SU; Nose/*SU; Rhinoplasty/*MT. .T Advances in nasal tip surgery. The lateral crural steal. .P JOURNAL ARTICLE. .W Increasing nasal tip projection, rotation, and definition have classically been attempted through a variety of lobular cartilage incising or excising techniques. Resultant long-term complications, including bossing, alar notching, pinched tips, and alar collapse, have occasionally resulted from the use of these techniques. The majority of these complications have arisen secondary to a loss of structural support following the interruption of the lower lateral cartilages. This article describes the "lateral crural steal," a method of increasing nasal tip projection and nasal tip rotation while preserving the integrity of the lobular cartilage complex. The procedure uses the external rhinoplasty approach for exposure. By elevating both the dorsal and the vestibular skin from the domes of the lobular cartilages, the lateral crura may be advanced onto the medial crura to further project the nasal tip and to reorient the tip upward. This technique along with its philosophy and long-term follow-up results are presented. .A Kridel RW; Konior RJ; Shumrick KA; Wright WK. .I 200442 .U 90000783 .S Arch Otolaryngol Head Neck Surg 9001; 115(10):1217-24 .M Acoustic Impedance Tests/AE/MT; Audiometry, Pure-Tone; Child; Child, Preschool; Chronic Disease; Comparative Study; Ear Diseases/ET; Follow-Up Studies; Hearing Loss, Partial/EP; Human; Infant; Middle Ear Ventilation/*/AE; Otitis Media with Effusion/PP/*SU; Random Allocation; Recurrence; Support, U.S. Gov't, P.H.S.; Tympanic Membrane/*SU. .T Myringotomy with and without tympanostomy tubes for chronic otitis media with effusion. .P JOURNAL ARTICLE. .W We studied 109 children with otitis media with effusion of 2 months' duration or longer that was unresponsive to medical management. Eighty-six subjects who had neither "significant" hearing loss nor defined symptoms were randomly assigned to receive myringotomy, myringotomy with tympanostomy tube insertion, or no surgery, and 23 subjects with significant hearing loss, defined symptoms, or both were randomly assigned to receive either myringotomy or myringotomy with tube insertion. Myringotomy with tube insertion provided more disease-free time and better hearing than either myringotomy alone or no surgery; however, some subjects who underwent myringotomy with tube insertion developed otorrhea or persistent perforation of the tympanic membrane. Myringotomy offered no advantage over no surgery regarding percent of time with middle-ear effusion, number of acute otitis media episodes, and number of subsequent surgical procedures. These results may not properly be extrapolated to less severely affected children. .A Mandel EM; Rockette HE; Bluestone CD; Paradise JL; Nozza RJ. .I 200443 .U 90000784 .S Arch Otolaryngol Head Neck Surg 9001; 115(10):1225-6 .M Bacterial Infections/*ET; Child; Child, Preschool; Ear Diseases/*ET; Human; Infant; Middle Ear Ventilation/*AE; Suppuration. .T Bacteriology of otorrhea from tympanostomy tubes. .P JOURNAL ARTICLE. .W Culture results from 100 consecutive cases of otorrhea from tympanostomy tubes are presented. In children younger than 3 years, the culture results are very similar to those seen in patients with acute otitis media who do not have tubes. In children older than 3 years, the flora resembles that of external otitis. Suggestions for treatment are made. .A Schneider ML. .I 200444 .U 90000785 .S Arch Otolaryngol Head Neck Surg 9001; 115(10):1227-30 .M Audiometry, Pure-Tone; Blood Viscosity/*; Hearing Loss, Sensorineural/*BL/PP; Human; Male; Middle Age; Rheology. .T Blood viscosity and hearing levels in the Caerphilly Collaborative Heart Disease Study. .P JOURNAL ARTICLE. .W Data from 342 men who are participants in the Caerphilly Collaborative Heart Disease Study were used to replicate a previous report of a significant relationship between measures of whole-blood viscosity and hearing levels in persons with sensorineural hearing impairment. In the unselected data, there were significant relationships between measures of whole-blood viscosity at high shear rates and hearing threshold levels at 2000 and 4000 Hz, even after accounting for the effects of age and socioeconomic group. In a subset of the data containing 124 persons selected on the basis of likely sensorineural hearing impairment, there were significant relationships between whole-blood viscosity and hearing level at all frequencies, with stronger effects at the higher frequencies. The data support the contention of a potentially important relationship between whole-blood viscosity and sensorineural hearing impairment. .A Gatehouse S; Gallacher JE; Lowe GD; Yarnell JW; Hutton RD; Ising I. .I 200445 .U 90000786 .S Arch Otolaryngol Head Neck Surg 9001; 115(10):1231-3 .M Cholesteatoma/CO/*DI; Chronic Disease; Comparative Study; Ear Diseases/CO/*DI; Human; Magnetic Resonance Imaging/*; Otitis Media/*; Predictive Value of Tests; Prospective Studies; Tomography, X-Ray Computed/*. .T Comparison of computed tomography and magnetic resonance imaging in chronic otitis media with cholesteatoma. .P JOURNAL ARTICLE. .W We prospectively studied 10 patients with chronic otitis media suspected of having cholesteatoma with computed tomography and magnetic resonance imaging to assess which imaging modality would be most specific in predicting the presence of cholesteatoma. The interpretation of images was then correlated with the operative findings. In 9 of the 10 cases, computed tomography accurately predicted the extent and destructiveness of the disease but did not consistently differentiate between cholesteatoma and associated granulation tissue. In 2 of the 10 cases, the T1-weighted magnetic resonance imaging demonstrated high signal, suggestive of cholesteatoma. In one case, magnetic resonance imaging predicted cholesteatoma on the basis of bony destruction. However, in 7 of 10 cases the scan was nonspecific for cholesteatoma. We conclude that high-resolution computed tomography remains the primary imaging modality for chronic otitis media. .A Koltai PJ; Eames FA; Parnes SM; Wood GW; Bie B. .I 200446 .U 90000789 .S Arch Otolaryngol Head Neck Surg 9001; 115(10):1244-7 .M Cerebellar Neoplasms/*DI; Cerebellopontine Angle/*; Contrast Media/*; DTPA; Human; Image Enhancement; Magnetic Resonance Imaging/*MT; Meningeal Neoplasms/*DI; Meningioma/*DI; Neuroma, Acoustic/*DI; Organometallic Compounds; Predictive Value of Tests; Tomography, X-Ray Computed. .T Gadolinium. The new gold standard for diagnosing cerebellopontine angle tumors. .P JOURNAL ARTICLE. .W All physicians involved with the diagnosis and management of patients with tumors in the temporal bone and cerebellopontine angle are faced with the challenge removing these tumors while preserving hearing. Part of the challenge is to make the diagnosis while the tumor is still small enough to attempt a hearing-conservation surgical approach. Air-contrast (air cisternography) computed tomography is the "gold standard" by which all techniques of diagnosis are compared. Most physicians, however, are reluctant to use this test as a screen for tumors because of the associated morbidity, time, and expense. We present three case reports of contrast-enhanced magnetic resonance imaging for the detection of small intracanalicular or cerebellopontine angle tumors, and review the literature of this new and exciting technology. We feel that gadolinium-enhanced magnetic resonance imaging is now the procedure of choice for evaluating patients with suspected temporal bone tumors. .A Sidman JD; Carrasco VN; Whaley RA; Pillsbury HC 3d. .I 200447 .U 90000790 .S Arch Otolaryngol Head Neck Surg 9001; 115(10):1248-9 .M Aged; Aged, 80 and over; Carcinoma, Basal Cell/*SU; Case Report; Human; Male; Nose Neoplasms/*SU; Wound Healing/*. .T Secondary intention healing. The primary approach for management of selected wounds. .P JOURNAL ARTICLE. .W Secondary intention healing is an ancient and well-established method of wound management. Since the advent of various reconstructive techniques, it is often forgotten as a valuable alternative to immediate surgical reconstruction of wounds. In certain situations the cosmetic and functional results of secondary intention healing are equal to the results of more complex reconstructive surgery. We describe a case in which remarkable results were obtained from spontaneous healing of a facial wound. .A Diwan R; Tromovitch TA; Glogau RG; Stegman SJ. .I 200448 .U 90000791 .S Arch Otolaryngol Head Neck Surg 9001; 115(10):1250-2 .M Carcinoma, Squamous Cell/RT; Case Report; Female; Fibrosarcoma/*ET; Human; Mandibular Neoplasms/*ET; Middle Age; Neoplasms, Radiation-Induced/*; Radiation Dosage; Tongue Neoplasms/RT. .T Fibrosarcoma of the mandible following supravoltage irradiation. Report of a case. .P JOURNAL ARTICLE. .W Supravoltage irradiation is commonly thought not to be carcinogenic. Several recent studies question this concept, as does our case report. A 50-year-old woman with stage 1 squamous carcinoma of the left side of the tongue was treated in 1973 with 73 Gy of supravoltage irradiation. Twelve years later a painful, ulcerated lesion that eventually was shown to be fibrosarcoma developed in the contralateral mandible. The fibrosarcoma in this case fulfills all criteria for diagnosing radiation-induced neoplasia and demonstrates that supravoltage irradiation, like other forms of irradiation, can cause malignancy. The occasional occurrence of sarcoma should be recalled during follow-up of patients treated with supravoltage radiation. Similarly, the possibility of radiation-induced tumors should be considered in planning treatment for younger patients with tumors that can be treated equally well by surgery or irradiation. .A Moloy PJ; Kowal KA; Siegel WM. .I 200449 .U 90000792 .S Arch Otolaryngol Head Neck Surg 9001; 115(10):1253 .M Acoustic Impedance Tests; Audiometry/*MT; Brain Stem/*PH; Cleft Lip/*PP; Cleft Palate/*PP; Clinical Protocols; Human; Infant, Newborn; Middle Ear Ventilation; Time Factors. .T A preliminary report on the use of auditory brain-stem response audiometry and the timing of tympanotomy with pressure equalization tube insertion in cleft palate neonates. .P JOURNAL ARTICLE. .A Pickard RE; Harrison RJ; Widen J; Karbowski L; Peterson EA. .I 200450 .U 90000793 .S Arch Otolaryngol Head Neck Surg 9001; 115(10):1254 .M Airway Obstruction/*ET; Cartilage Diseases/CO; Case Report; Cysts/*CO; Epiglottis/*; Human; Male; Middle Age. .T Asphyxia due to a sialocyst [letter] .P LETTER. .A Melcher MP. .I 200451 .U 90000795 .S Arch Otolaryngol Head Neck Surg 9001; 115(10):1256-7, 1259 .M Adult; Carcinoma, Mucinous/*PA; Case Report; Ethmoid Sinus/*PA; Female; Human; Paranasal Sinus Neoplasms/*PA. .T Pathologic quiz case 2. Signet-ring cell adenocarcinoma of the ethmoid sinuses. .P JOURNAL ARTICLE. .A Costantino PD; Jones K; Atiyah RA. .I 200452 .U 90000796 .S Arch Otolaryngol Head Neck Surg 9001; 115(10):1256-8 .M Amyloidosis/*PA; Case Report; Goiter/*PA; Human; Male; Middle Age. .T Pathologic quiz case 1. Amyloid goiter. .P JOURNAL ARTICLE. .A Talmi YP; Gal R; Finkelstein Y; Gafter U; Zohar Y. .I 200453 .U 90000980 .S Br Heart J 9001; 62(3):165-70 .M Adult; Aged; Atropine/PD; Electrocardiography; Female; Heart/*IR; Heart Rate/DE; Human; Male; Middle Age; Myocardial Infarction/*PP; Support, Non-U.S. Gov't; Time Factors; Vagus Nerve/DE/*PP. .T Cardiac parasympathetic activity during the early hours of acute myocardial infarction. .P JOURNAL ARTICLE. .W Cardiac parasympathetic activity was assessed in 21 patients during the first 24 hours of acute myocardial infarction by measuring abrupt beat by beat changes in RR interval, which are expressed as "RR counts". Eleven patients had inferior wall infarction and 10 had anterior wall myocardial infarction. The whole recording period was analysed in 11 patients (five inferior and six anterior), and intermittent hourly periods were analysed in all 21 subjects. Mean RR counts were significantly lower in patients with anterior than inferior infarction, and below the normal range. Although mean heart rates were faster in the group with anterior infarction, there was a dissociation between RR counts and mean heart rate that was consistent with RR interval variability being an independent measure of parasympathetic activity. This study indicates that cardiac parasympathetic activity during acute myocardial infarction can be simply and reliably assessed from continuous electrocardiographic recordings, and it showed significantly lower cardiac parasympathetic activity in patients with anterior infarction. .A McAreavey D; Neilson JM; Ewing DJ; Russell DC. .I 200454 .U 90000981 .S Br Heart J 9001; 62(3):171-6 .M Adolescence; Aortic Valve Insufficiency/DI/*ET; Cardiomyopathy, Hypertrophic/*CO; Echocardiography, Doppler; Female; Human; Male; Middle Age. .T Aortic regurgitation associated with hypertrophic cardiomyopathy: a colour Doppler echocardiographic study. .P JOURNAL ARTICLE. .W The frequency, severity, and cause of aortic regurgitation were assessed by colour Doppler and cross sectional echocardiography in 87 patients (mean SD) age 57 (12) years) with hypertrophic cardiomyopathy, and 48 age matched controls (57 (8) years). Aortic regurgitant murmurs were recorded in only three of 87 patients and in none of the controls. Colour Doppler echocardiography showed an aortic regurgitant signal in 20 (23%) of the patients and three (6%) of the 48 controls. The colour Doppler signals typical of aortic regurgitation were limited to the left ventricular outflow tract. There were no significant differences between patients with hypertrophic cardiomyopathy with and without aortic regurgitation in terms of age (59 years v 56 years), blood pressure (140/84 mm Hg v 136/80 mm Hg), aortic diameter (34 mm v 33 mm), or frequency of calcification of the aortic valve (15% v 10%) and of systolic anterior motion of the mitral valve with mitral-septal contact (25% v 16%). On cross sectional echocardiograms, the degree of septal protrusion into the left ventricular outflow tract during systole was significantly more prominent (15 v 10 mm), and the portion of the basal septum that protruded most deeply into the left ventricular outflow tract was significantly closer to the aortic annulus in patients with aortic regurgitation than in those without it (11 v 14 mm). Mild aortic regurgitation was found in almost a quarter of patients with hypertrophic cardiomyopathy. The regurgitation was related to the morphological abnormality of the left ventricular outflow tract. .A Shiota T; Sakamoto T; Takenaka K; Amano K; Hada Y; Hasegawa I; Suzuki J; Takahashi H; Sugimoto T. .I 200455 .U 90000982 .S Br Heart J 9001; 62(3):177-84 .M Adolescence; Adult; Blood Flow Velocity; Child; Echocardiography, Doppler/*; Human; Male; Mitral Valve/*PH; Support, Non-U.S. Gov't. .T Cross sectional early mitral flow velocity profiles from colour Doppler. .P JOURNAL ARTICLE. .W Instantaneous cross sectional flow velocity profiles from early mitral flow in 10 healthy men were constructed by time interpolation of the velocity data from each point in sequentially delayed two dimensional digital Doppler ultrasound maps. This interpolation allows correction of the artificially produced skewness of velocities across the flow sector caused by the time taken to scan the flow sector for velocity recording of pulsatile blood flow. These results suggested that early mitral flow studied in an apical four chamber view is variably skewed both at the leaflet tips and at the annulus. The maximum flow velocity overestimated the cross sectional mean velocity at the same time by a factor of 1.2-2.2. Also the maximum time velocity integral overestimated the cross sectional mean time velocity integral to the same extent. This cross sectional skew must be taken into account when calculation of blood flow is based on recordings with pulsed wave Doppler ultrasound from a single sample volume. .A Samstad SO; Torp HG; Linker DT; Rossvoll O; Skjaerpe T; Johansen E; Kristoffersen K; Angelsen BA; Hatle L. .I 200456 .U 90000983 .S Br Heart J 9001; 62(3):185-94 .M Acromegaly/*CO/PP; Adult; Aged; Arrhythmia/CO/PP; Echocardiography; Electrocardiography; Electrocardiography, Ambulatory; Female; Heart Enlargement/CO/PP; Human; Hypertension/CO/PP; Male; Middle Age; Myocardial Diseases/*CO/PP/RI; Radionuclide Ventriculography; Systole. .T Subclinical cardiac dysfunction in acromegaly: evidence for a specific disease of heart muscle [see comments] .P JOURNAL ARTICLE. .W Acromegaly is associated with an increased cardiac morbidity and mortality, but it is not clear whether this is the result of increased incidence of hypertension and coronary heart disease or of a specific disease of heart muscle. Thirty four acromegalic patients were studied by non-invasive techniques. Seven of these patients had raised plasma concentrations of growth hormone at the time of study; three were newly diagnosed and had not received any treatment. Hypertension was present in nine (26%) but only three (9%) had electrocardiographic left ventricular hypertrophy. Echocardiography showed ventricular hypertrophy in 12 (48%) and increased left ventricular mass in 17 (68%) patients. Holter monitoring detected important ventricular arrhythmias in 14 patients. Thallium-201 scanning showed evidence for coronary heart disease in eight patients. Systolic time intervals were normal except when there was coexistent ischaemic heart disease. A comparison between 19 acromegalic patients with no other detectable cause of heart disease and 22 age matched controls showed appreciably abnormal left ventricular diastolic function in the group with acromegaly. The abnormalities shown did not correlate with left ventricular mass or wall thickness. There was no difference in diastolic function between patients with active acromegaly and those with treated acromegaly. Hypertensive acromegalic patients had worse diastolic function than hypertensive controls, suggesting that hypertension may further impair the left ventricular diastolic abnormality in acromegaly. This is the first study to find evidence of subclinical cardiac diastolic dysfunction in acromegaly and it supports the suggestion that there is a specific disease of heart muscle in acromegaly. .A Rodrigues EA; Caruana MP; Lahiri A; Nabarro JD; Jacobs HS; Raftery EB. .I 200457 .U 90000984 .S Br Heart J 9001; 62(3):195-203 .M Adenosine/AE/DU/*TU; Adolescence; Adult; Aged; Electrocardiography; Female; Human; Male; Middle Age; Recurrence; Tachycardia/DI/*DT. .T Value and limitations of adenosine in the diagnosis and treatment of narrow and broad complex tachycardias. .P JOURNAL ARTICLE. .W The diagnostic and therapeutic potential of intravenous adenosine was studied in 64 patients during 92 episodes of regular sustained tachycardia. In 40 patients who had narrow complex tachycardias (QRS less than 0.12 s) adenosine (2.5-25 mg) restored sinus rhythm in 25 with junctional tachycardias (46 of 48 episodes) and produced atrioventricular block to reveal atrial or sinus tachycardia in 15. In 24 patients with broad complex tachycardias (QRS greater than or equal to 0.12 s) adenosine terminated the tachycardias in six patients and revealed atrial or sinus arrhythmias in four. The tachycardias persisted in 14 patients despite doses up to 20 mg, but adenosine allowed the diagnosis of ventricular tachycardia with retrograde atrial activation in two patients by producing transient ventriculoatrial dissociation. Diagnosis based on adenosine induced atrioventricular nodal block was correct in all patients with narrow complex tachycardias and in 92% of those with broad complex tachycardias, compared with correct electrocardiographic diagnoses in 90% and 75% respectively. Adenosine gave diagnostic information additional to the electrocardiogram in 25%. The response to adenosine in broad complex tachycardias identified those of supraventricular origin with 90% sensitivity, 93% specificity, and 92% predictive accuracy. Adenosine restored sinus rhythm in all patients with junctional reentrant tachycardias, but in 10 (35%) the arrhythmias recurred within two minutes. Symptomatic side effects (dyspnoea, chest pain, flushing, headache) were reported by 40 (63%) patients and, although transient, were severe in 23 (36%). There were ventricular pauses of over 2 s in 16% of patients, the longest pause being 6.1 s.(ABSTRACT TRUNCATED AT 250 WORDS) .A Rankin AC; Oldroyd KG; Chong E; Rae AP; Cobbe SM. .I 200458 .U 90000985 .S Br Heart J 9001; 62(3):204-11 .M Adenosine/AE/DU/*TU; Adolescence; Child; Child, Preschool; Female; Human; Infant; Infant, Newborn; Male; Tachycardia, Supraventricular/DI/*DT. .T Efficacy and safety of adenosine in the treatment of supraventricular tachycardia in infants and children. .P JOURNAL ARTICLE. .W One hundred and seventeen episodes of supraventricular tachycardia in 50 children, including 28 infants, were treated with intravenous adenosine. Adenosine was prepared in a sterile solution of 0.9% saline (1 mg/ml) and given in incremental doses of 0.05 mg/kg every two minutes to a maximum of 0.25 mg/kg. Ninety of the 117 episodes were terminated. This included 88 of the 102 episodes of junctional tachycardia (79 of the 92 episodes of atrioventricular reentry tachycardia, seven of the eight episodes of atrioventricular nodal reentry tachycardia, and both of the episodes of long R-P' tachycardia). Only one of four episodes of His bundle tachycardia and one of the eight episodes of ectopic atrial tachycardia were terminated. None of the three episodes of atrial flutter were terminated. Side effects were frequent but mild and included transient complete atrioventricular block (less than 6 s), sinus bradycardia (less than 40 s), ventricular extrasystoles, flushing, nausea, headache, and respiratory disturbance. Reinitiation (within 5 s) of supraventricular tachycardia occurred in 13 of the terminated episodes. Although reinitiation limited its clinical efficacy in some patients, intravenous adenosine offered a safe and efficient method of rapid termination of most episodes of supraventricular tachycardia and in some cases facilitated diagnosis of the mechanism. .A Till J; Shinebourne EA; Rigby ML; Clarke B; Ward DE; Rowland E. .I 200459 .U 90000986 .S Br Heart J 9001; 62(3):212-6 .M Adolescence; Balloon Dilatation/*; Child; Child, Preschool; Echocardiography, Doppler/*; Human; Infant; Infant, Newborn; Pulmonary Valve Stenosis/PP/*TH. .T Variability of the Doppler gradient in pulmonary valve stenosis before and after balloon dilatation. .P JOURNAL ARTICLE. .W The variability of the valve gradient measured by Doppler in pulmonary stenosis was compared with the variability of the gradient measured at catheterisation in 42 infants and children undergoing catheterisation with a view to balloon dilatation of the pulmonary valve. The maximum value measured by Doppler when the patient was unsedated was significantly higher than that measured when the patient was sedated for catheterisation, and the maximum gradient was significantly higher shortly after than several days later. In a patient with pronounced infundibular obstruction after dilatation the Doppler signal clearly showed that the obstruction was dynamic, with a superimposed lower fixed signal that correctly predicted the final low gradient. The Doppler gradient in an alert and unsedated patient may be a better measure of the true physiological value. The highest Doppler value so obtained is a more appropriate indicator of the need for balloon dilatation than a single catheter measurement. The result of dilatation is best assessed by Doppler measurement at least a day after the procedure. .A Lim MK; Houston AB; Doig WB; Lilley S; Murtagh EP. .I 200460 .U 90000987 .S Br Heart J 9001; 62(3):217-9 .M Case Report; Drainage/*; Human; Infant; Male; Pericardial Effusion/*TH; Postoperative Complications/*TH; Recurrence; Streptokinase/AD/*TU. .T Use of streptokinase to aid in drainage of postoperative pericardial effusion. .P JOURNAL ARTICLE. .W A case of cardiac tamponade secondary to a late, loculated pericardial effusion after open pulmonary valvotomy is described. Percutaneous drainage of the effusion was aided by the infusion of intrapericardial streptokinase. .A Cross JH; De Giovanni JV; Silove ED. .I 200461 .U 90000988 .S Br Heart J 9001; 62(3):220-1 .M Adolescence; Case Report; Electrocardiography; Female; Human; Pacemaker, Artificial; Tachycardia/*ET/TH; Tachycardia, Atrioventricular Nodal Reentry/*CO/TH; Tachycardia, Supraventricular/*CO. .T Development of multiform ventricular tachycardia during atrioventricular nodal reentrant tachycardia. .P JOURNAL ARTICLE. .W A woman of 18 presented with a supraventricular tachycardia, subsequently shown to be caused by atrioventricular nodal reentry, which abruptly deteriorated to a multiform ventricular tachycardia. She had not received any antiarrhythmic drugs nor did she have any of the disorders that are usually associated with this atypical ventricular tachycardia. .A Bennett DH; Coyle C. .I 200462 .U 90000989 .S Br Heart J 9001; 62(3):222-4 .M Case Report; Child, Preschool; Female; Human; Tricuspid Valve/*AB/SU. .T Straddling tricuspid valve without a ventricular septal defect. .P JOURNAL ARTICLE. .W A four year old girl with pulmonary atresia had a straddling tricuspid valve without an interventricular communication. The overriding tricuspid valve had two orifices, which connected with the right and the left ventricles. Valve tissue separated both orifices and was firmly connected to the crest of the ventricular septum, thus sealing off the expected interventricular communication. Surgical correction was performed and the outcome was satisfactory. .A Isomatsu Y; Kurosawa H; Imai Y. .I 200463 .U 90000990 .S Br Heart J 9001; 62(3):225-7 .M Adult; Case Report; Diagnosis, Differential; Heart Aneurysm/*DI/ET; Heart Ventricle; Human; Male; Myocardial Infarction/CO; Rupture, Spontaneous. .T Subacute rupture of a pseudoaneurysm formed by late rupture of a true left ventricular aneurysm. .P JOURNAL ARTICLE. .W A man aged 34 in whom rupture of a true aneurysm at least four weeks after acute myocardial infarction led to the development of a pseudoaneurysm is described. Because the pseudoaneurysm ruptured subacutely and the haemodynamic, clinical, and echocardiographic signs were not consistent, diagnosis of the cardiac rupture was delayed. Operative repair was successful, but the patient died. .A Goudevenos J; Parry G; Morritt GN. .I 200464 .U 90000991 .S Br Heart J 9001; 62(3):228-9 .M Anastomosis, Surgical; Angioplasty, Transluminal/*; Blood Vessel Prosthesis/*; Case Report; Female; Graft Occlusion, Vascular/*TH; Heart Defects, Congenital/SU; Human; Infant; Polytetrafluoroethylene; Postoperative Complications/*TH. .T Balloon dilatation of a stenosed modified (polytetrafluoroethylene) Blalock-Taussig shunt. .P JOURNAL ARTICLE. .W A 17 month old girl with tricuspid atresia, ventricular septal defect, subvalvar and valvar pulmonary stenosis, and increasing cyanosis had angiographic evidence of proximal stenosis of a right modified (5 mm diameter) Blalock-Taussig shunt. She underwent palliative balloon angioplasty with a 6 mm Schneider balloon catheter. Successful dilatation was achieved without complication. Four months later there was subjective clinical improvement with a rise in systemic arterial saturation. Repeat angiography showed patency of the shunt without restenosis or formation of an aneurysm. .A Parsons JM; Ladusans EJ; Qureshi SA. .I 200465 .U 90000993 .S Br Heart J 9001; 62(3):237-8 .M Diastole/*; Heart Ventricle/RI; Human; Hypertension/*PP/RI; Myocardial Contraction/*. .T Radionuclide measurements of diastolic function for assessing early left ventricular abnormalities in the hypertensive patient [letter; comment] .P COMMENT; LETTER. .A Schneeweiss A. .I 200466 .U 90001523 .S Blood 9001; 74(5):1477-80 .M Adult; Anemia, Aplastic/SU; Antibody-Dependent Cell Cytotoxicity; Bone Marrow Transplantation/*; Case Report; Colony-Forming Units Assay; Cytotoxicity, Immunologic/*; Female; Graft Rejection/*; Hematopoietic Stem Cells/CY; Human; Killer Cells, Natural/IM; Leukemia/SU; Male; Support, U.S. Gov't, P.H.S.; T-Lymphocytes/*IM; Transplantation, Homologous. .T Antibody-mediated marrow failure after allogeneic bone marrow transplantation. .P JOURNAL ARTICLE. .W Marrow graft failure observed in association with histocompatibility differences between donor and recipient is often attributed to rejection mediated by host-derived cytolytic T lymphocytes. The data presented in this report indicate that persistent host antibodies specific for donor antigen may also mediate graft failure, either by antibody-dependent cell-mediated cytotoxicity (ADCC), or complement-mediated cytotoxicity. In the case of HLA Class I disparity, where all donor cells express the target antigen, the presence of alpha-donor antibody was associated with complete graft failure and death. In the case of ABO blood group antigen disparity, the presence of alpha-donor antibody resulted in erythroid hypoplasia. The latter cases proved informative insofar as they established that host antibodies could persist for more than 18 months after chemoradiotherapy and impair marrow function. .A Barge AJ; Johnson G; Witherspoon R; Torok-Storb B. .I 200467 .U 90001524 .S Blood 9001; 74(5):1481-5 .M Acetylcholinesterase/*BL; Adenosine Triphosphate/BL; Adult; Blood Proteins/*ME; Calcium/PD; Erythrocyte Membrane/DE/*ME/UL; Glycolipids/*BL; Human; Kinetics; Membrane Proteins/IP/*ME; Phosphatidylinositols/*BL; Protein Binding; Support, U.S. Gov't, P.H.S.. .T Enrichment of two glycosyl-phosphatidylinositol-anchored proteins, acetylcholinesterase and decay accelerating factor, in vesicles released from human red blood cells. .P JOURNAL ARTICLE. .W Several proteins are attached to the cell membrane by a glycosyl-phosphatidylinositol (GPI) anchor. In this report, we show that during vesiculation of human RBCs in vitro, two of these proteins, acetylcholinesterase and decay accelerating factor, redistribute on the cell surface and become enriched in the released vesicles. As a result, the remnant cells are depleted of these proteins. We suggest that alterations in the architecture of the RBC membrane that precede vesiculation lead to selective polarization of GPI-anchored proteins within the domain of the membrane destined to become a vesicle. Since vesiculation occurs in many cell types, and if the loss of GPI-anchored proteins accompanies this process, it may have important biologic significance. .A Butikofer P; Kuypers FA; Xu CM; Chiu DT; Lubin B. .I 200468 .U 90001525 .S Blood 9001; 74(5):1486-90 .M Alleles; Base Sequence; DNA/GE; Exons; Factor X/*GE; Factor X Deficiency/BL/*GE; Female; Gene Amplification; Human; Hypoprothrombinemias/*GE; Male; Molecular Sequence Data; Mutation/*; Promoter Regions (Genetics); Restriction Mapping; RNA Splicing; Support, U.S. Gov't, P.H.S.. .T Molecular characterization of human factor XSan Antonio. .P JOURNAL ARTICLE. .W Enzymatic amplification technique was used to isolate all eight exons and sequences around the splice junctions, putative promoter, and polyadenylation sites of human factor X DNA from a patient with factor X deficiency. Two genetic changes in factor X have been observed in this patient. The patient is most likely a compound heterozygote since there is only 14% activity associated with factor X. A point mutation that resulted in the substitution of cysteine (TGC) for arginine (CGC) at amino acid 366 was found in exon VIII of one allele of the factor X gene. This mutation, which occurs in the catalytic domain, can affect the formation of a disulfide bridge and thus could result in a reduction in factor X activity. Sequencing all the regions revealed a second mutation: a deletion of one nucleotide (TCCT to TCT) in exon VII that would cause a frame shift at amino acid 272 followed by termination. We have also shown that the point mutation in exon VIII creates an ApaL1 restriction site and destroys the HinP1 site. Enzymatic DNA amplification followed by restriction digestion provides a quick, reliable, and sensitive method for carrier detection and antenatal diagnosis in affected kindreds. This is the first characterization of factor X deficiency at the molecular level. We propose to name this mutation Factor XSan Antonio. .A Reddy SV; Zhou ZQ; Rao KJ; Scott JP; Watzke H; High KA; Jagadeeswaran P. .I 200469 .U 90001528 .S Blood 9001; 74(5):1507-16 .M Adult; Antineoplastic Agents, Combined/*AE/TU; Blood Cell Count; Bone Marrow Transplantation/*; Busulfan/AD/AE; Cyclophosphamide/AD/AE; Female; Follow-Up Studies; Human; Leukemia, Myelocytic, Acute/*DT/SU; Male; Probability; Support, Non-U.S. Gov't; Transplantation, Autologous. .T Acute toxicity and first clinical results of intensive postinduction therapy using a modified busulfan and cyclophosphamide regimen with autologous bone marrow rescue in first remission of acute myeloid leukemia [see comments] .P JOURNAL ARTICLE. .W The combination of high-dose busulfan (16 mg/kg) and 200 mg/kg cyclophosphamide is gaining increasing significance as a preparative regimen prior to autologous, syngeneic, or allogeneic marrow transplantation. A new regimen of high-dose busulfan in conjunction with a reduced dose of 120 mg/kg cyclophosphamide has recently been described as a preparative regimen prior to allogeneic transplantation. To determine the drug-related nonhematologic toxic effects of this new regimen without confounding factors associated with allogeneic transplantation, we conducted a pilot study using this new regimen in 20 patients with acute myeloid leukemia (AML) in first remission prior to autologous unpurged marrow transplantation. All patients experienced transient non-life-threatening acute drug-related toxicity with skin reactions in 20 (100%), nausea and vomiting in 20 (100%), oral mucositis in 18 (90%), hepatic functional impairment in 17 (85%), hemorrhagic cystitis in three (15%), and generalized seizures in two (10%) of these patients, respectively. Two procedural, fatal complications resulted from infectious causes that were not directly related to the speed of hematopoietic reconstitution or the toxicity of the preparative regimen. The 3-year event-free survival estimate (55% +/- 11%) and probability of leukemic recurrence (38% +/- 11%) attained with this new regimen in recipients of autografts in first remission of AML are promising and challenge comparisons with preparative regimens employing combinations of cytotoxic agents or total body irradiation (TBI). .A Beelen DW; Quabeck K; Graeven U; Sayer HG; Mahmoud HK; Schaefer UW. .I 200470 .U 90001532 .S Blood 9001; 74(5):1537-44 .M Animal; B-Lymphocytes/IM; Bone Marrow/CY; Bone Marrow Transplantation; Cells, Cultured; Colony-Forming Units Assay; Cytotoxicity, Immunologic; Female; Hematopoietic Stem Cells/CY/TR; Immunity, Cellular; Immunologic Deficiency Syndromes/*IM/SU; Male; Mice; Mice, Inbred BALB C; Mice, Mutant Strains; Spleen/IM; Support, Non-U.S. Gov't; T-Lymphocytes, Cytotoxic/IM. .T Use of scid mice to identify and quantitate lymphoid-restricted stem cells in long-term bone marrow cultures. .P JOURNAL ARTICLE. .W Mice homozygous for an autosomal recessive scid (severe combined immune deficiency) mutation on chromosome 16 exhibit a defect that specifically impairs lymphoid differentiation but not myelopoiesis. Consequently such mice are deficient in both humoral and cell-mediated immune functions. Despite their defect, scid mice survive under pathogen-free conditions and are fertile. The mutation does not impair the hematopoietic microenvironment necessary for lymphoid differentiation, since these mice can be cured with grafts of normal bone marrow (BM) or cells from long-term BM cultures (LTBMC); however, reconstitution requires sublethal (400 cGy) irradiation of recipients. Engraftment with cells from LTBMC gave near-normal levels of colony-forming B cells (CFU-B) in spleen and BM of the recipients by 6 weeks postgrafting. Since LTBMC are devoid of all mature B and pre-B cells but contain stem cells that restore lymphoid function in scid mice, we used a limiting-dilution assay to characterize and enumerate the number of stem cells in LTBMC capable of restoring lymphoid function. Curing was determined by the CFU-B-cell assay, since CFU-B are not detectable in normal scid mice. The results indicate that fewer cells from LTBMC than from fresh BM are required to obtain lymphoid reconstitution. As few as 10(3) LTBMC cells can repopulate significant B- and T-cell function in scid recipients. From these results we conclude that scid mice can be used as recipients to quantify lymphoid-restricted stem cells and that there is a functional separation of lymphoid- and myeloid-restricted stem cells in LTBMC with an enrichment for lymphoid-restricted stem cells in these cultures. .A Fulop GM; Phillips RA. .I 200471 .U 90001533 .S Blood 9001; 74(5):1545-51 .M Animal; Cell Line; Cells, Cultured; Hematopoietic Stem Cells/*CY/DE; Human; Interleukin-1/PD; Interleukin-3/PD; Interleukin-6/*PD; Megakaryocytes/*CY/DE; Mice; Mice, Inbred C3H; Recombinant Proteins/PD; Support, Non-U.S. Gov't. .T Regulation of megakaryocyte development by interleukin-6. .P JOURNAL ARTICLE. .W Megakaryocytes develop in densely seeded normal mouse bone marrow (BM) cells cultured in agar or in liquid medium. This formation of megakaryocytes is enhanced by the myeloid differentiation-inducing protein MGI-2, which we have shown to be interleukin-6 (IL-6). Monoclonal antibody (MoAb) that specifically neutralizes mouse IL-6 but not human IL-6 inhibited megakaryocyte development in cells cultured either with or without the addition of mouse IL-6 but did not inhibit megakaryocyte development induced by human IL-6. This MoAb to mouse IL-6 that does not neutralize mouse IL-3 also inhibited mouse IL-3-induced megakaryocyte development. Antibody to mouse GM-CSF did not inhibit the formation of megakaryocytes. The results show that the induction of megakaryocyte development by IL-3 is due to the production of IL-6 in the BM cultures. The present experiments demonstrate a new property of IL-6 and indicate that IL-6 is a regulatory protein of normal megakaryocyte development. .A Lotem J; Shabo Y; Sachs L. .I 200472 .U 90001534 .S Blood 9001; 74(5):1552-6 .M Anemia/*GE/SU; Animal; Biological Markers/AN; Bone Marrow Transplantation/*; Erythrocytes/*CY; Erythroid Progenitor Cells/*CY/DE; Hematopoiesis/*; Hematopoietic Stem Cells/*CY/RE; Kinetics; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Neutrophils/CY; Phosphoglycerate Kinase/AN; Species Specificity; Support, Non-U.S. Gov't. .T Different repopulation profile between erythroid and nonerythroid progenitor cells in genetically anemic W/Wv mice after bone marrow transplantation. .P JOURNAL ARTICLE. .W Repopulation kinetics of erythrocytes and neutrophils and replacement of hematopoietic progenitors were studied in genetically anemic (WB x C57BL/6)F1-W/Wv (WBB6F1-W/Wv) hosts after bone marrow transplantation from C57BL/6-bgJ/bgJ or C57BL/6-bgJ/bgJ;Pgk-1a/Y mice. Electrophoretic pattern of hemoglobin was used as a marker of donor-type erythrocytes, giant granules of bgJ/bgJ mice as a marker of donor-type neutrophils, and A-type phosphoglycerate kinase-1 (PGK-1) as a marker of hematopoietic colonies produced by donor-derived progenitor cells. Repopulation of donor-type erythrocytes was significantly faster than that of donor-type neutrophils. Moreover, the extent of replacement was greater for erythroid progenitor cells than for nonerythroid progenitor cells. When nonirradiated WBB6F1-W/Wv mice with B-type PGK-1 received 10(5) bone marrow cells from C57BL/6-bgJ/bgJ;Pgk-1a donors, only approximately 20% replacement of erythroid progenitor cells gave rise to total reconstitution of erythrocytes. The present result suggests that normal multipotential stem cells may preferentially differentiate into erythroid lineage cells in anemic WBB6F1-W/Wv hosts and that normal erythroid progenitor cells may suppress the differentiation of erythroid progenitors of WBB6F1-W/Wv hosts. .A Nakano T; Waki N; Asai H; Kitamura Y. .I 200473 .U 90001535 .S Blood 9001; 74(5):1557-62 .M Animal; Cell Differentiation; Cell Division; Cell Line; Embryo; Fibroblasts/CY/PH/RE; Growth Substances/*PH; Mast Cells/*CY; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Species Specificity; Support, Non-U.S. Gov't. .T Suppressive effect of Sl/Sld mouse embryo-derived fibroblast cell lines on diffusible factor-dependent proliferation of mast cells. .P JOURNAL ARTICLE. .W Two modes of mast cell growth are present, one dependent on diffusible growth factors (interleukins [IL] 3 and 4) and another dependent on contact with fibroblasts. The 3T3 fibroblast cell lines derived from WCB6F1-+/+ mouse embryos supported the proliferation of cultured mast cells (CMC), whereas the 3T3 fibroblast cell lines from WCB6F1-Sl/Sld mouse embryos did not. To investigate the relationship between growth factor-dependent and fibroblast-dependent growths of mast cells, we cocultured CMC and 3T3 fibroblasts in the presence of diffusible growth factors. WCB6F1-+/+ mouse embryo-derived 3T3 cells did not affect the growth factor-dependent proliferation of CMC, but WCB6F1-Sl/Sld mouse embryo-derived 3T3 cells significantly suppressed the proliferation. Close cell-to-cell contact was necessary for the suppression. The NWS1 fibroblast cell line was established from the spleen cells of an adult WBB6F1-+/+ mouse. Although the NWS1 cell line had no supporting effect on the proliferation of CMC in the absence of diffusible growth factors, it did not suppress the proliferation of CMC induced by the growth factors. The present result suggests that a product of mutant Sl genes may be involved in the suppressive activity of WCB6F1-Sl/Sld mouse embryo-derived 3T3 cells. .A Onoue H; Ebi Y; Nakayama H; Ru XM; Kitamura Y; Fujita J. .I 200474 .U 90001536 .S Blood 9001; 74(5):1563-70 .M Bone Marrow/*CY; Cell Separation; Cells, Cultured; Centrifugation, Density Gradient; Clone Cells; Hematopoiesis/*; Hematopoietic Stem Cells/*CY/PH; Human; HLA-DR Antigens/AN; Support, Non-U.S. Gov't. .T Characterization and partial purification of human marrow cells capable of initiating long-term hematopoiesis in vitro. .P JOURNAL ARTICLE. .W To develop a purification strategy for isolating the most primitive hematopoietic stem cells present in normal human marrow we have combined cell separation techniques with an assay for cells that initiate sustained hematopoiesis in vitro in the presence of irradiated human marrow adherent cells. These "feeders" were established by subculturing 2- to 6-week-old primary long-term marrow culture adherent layers at a density of 3 x 10(4) irradiated cells per square centimeter. Test "long-term culture (LTC)-initiating cells" were plated on top of the feeders and the cocultures then maintained as standard long-term marrow cultures with half-media changes and removal of half of the nonadherent cells each week. The total number of myeloid, erythroid, and multilineage clonogenic progenitors present after 5 weeks was used to provide a quantitative assessment of the number of LTC-initiating cells originally added. Using this assay, the density, light scatter, and two cell surface antigen properties of LTC-initiating cells have been defined and compared with cells capable of directly forming colonies in methylcellulose. While the majority of the clonogenic cells were found in the high forward light scatter (FLS) "blast" window, LTC-initiating cells had significantly lower FLS properties and in this respect were more similar to lymphocytes. LTC-initiating cells also expressed less HLA-DR antigen than clonogenic cells. The majority of LTC-initiating cells were found in the top 2% of the CD34 (My10) fluorescence profile, whereas clonogenic cells were found throughout the top 5% of the CD34 fluorescence profile. By combining low FLS, low orthogonal light scatter (OLS), low HLA-DR expression, and high CD34 expression, a population could be obtained that was enriched for LTC-initiating cells approximately 800-fold over unseparated marrow. This population contains only 0.06% of the marrow cells and 2% of the total clonogenic cells, but retains 50% to 60% of the LTC-initiating cells present in the original marrow. The ability to purify these two populations independently shows that the LTC and clonogenic assays identify distinct, although not necessarily nonoverlapping cell types in human marrow. Since clonogenic cells are derived from LTC-initiating cells, the LTC assay clearly detects a more primitive population. The availability of a simple approach that allows the purification of such cells by three orders of magnitude in high yield should be useful for the investigation of early events in hematopoiesis as well as for the definitive isolation of human hematopoietic stem cells with long-term in vivo repopulating potential. .A Sutherland HJ; Eaves CJ; Eaves AC; Dragowska W; Lansdorp PM. .I 200475 .U 90001537 .S Blood 9001; 74(5):1571-6 .M Animal; Comparative Study; Erythroid Progenitor Cells/*CY/DE; Erythropoiesis/*DE; Erythropoietin/*PD; Fetal Hemoglobin/*BI; Human; Interleukin-3/*PD; Kinetics; Macaca fascicularis; Papio; Recombinant Proteins/PD; Reference Values; Support, U.S. Gov't, P.H.S.. .T Effects of interleukin-3 and erythropoietin on in vivo erythropoiesis and F-cell formation in primates. .P JOURNAL ARTICLE. .W To test the in vivo cooperativity between interleukin-3 (IL-3) and erythropoietin (Epo) in stimulating erythropoiesis and hemoglobin F (HbF) production in primates, we administered recombinant human IL-3 and recombinant human Epo to baboons and macaques. The effect of these treatments was assessed by serial bone marrow cultures and by measuring HbF production in the progeny of bone marrow progenitors and in peripheral-blood reticulocytes. Administration of IL-3 alone to hematologically normal or anemic baboons produced an early increase in erythroid colony-forming units (CFUe) and erythroid clusters (e-clusters) with an increase in reticulocyte counts and a late increment in the relative frequency of erythroid burst-forming units (BFUe). In parallel to the increase in peripheral-blood reticulocytes, IL-3 increased the frequency of F reticulocytes in the normal and anemic animals. When administration of IL-3 was followed by administration of Epo, expansion in all classes of erythroid progenitors and increase in reticulocytes occurred, beyond the levels observed when the animals were treated with Epo alone. The combination of IL-3 and Epo, however, did not increase consistently the rate of F reticulocytes beyond the level induced by Epo alone. These results suggest that IL-3 enhances the effect of Epo on erythropoiesis, but the combination of the two growth factors does not lead to a preferential and significant enhancement of HbF production. .A Umemura T; al-Khatti A; Donahue RE; Papayannopoulou T; Stamatoyannopoulos G. .I 200476 .U 90001538 .S Blood 9001; 74(5):1577-82 .M Adult; Blood Coagulation/*DE; Chondroitin/*AA; Dermatan Sulfate/BL/*PD/PK; Dose-Response Relationship, Drug; Female; Human; Male; Metabolic Clearance Rate; Partial Thromboplastin Time; Support, Non-U.S. Gov't; Thrombin Time. .T Pharmacodynamics and pharmacokinetics of dermatan sulfate in humans. .P JOURNAL ARTICLE. .W Dermatan sulfate (DS), a catalyst of the thrombin-heparin cofactor II interaction, has antithrombotic activity and is devoid of significant hemorrhagic risk in several animal models. We investigated the pharmacodynamic and pharmacokinetic properties of DS in humans. DS was injected in single bolus intravenous injections of four increasing doses (0.5, 1, 1.5, 2 mg/kg) to six healthy volunteers. The resulting anticoagulant activities were assessed by the activated partial thromboplastin time (APTT) and the thrombin clotting time (TCT). There were dose-dependent prolongations of the APTT and TCT, and the anticoagulant activities disappeared in less than three hours. The pharmacokinetic parameters were calculated from the plasma concentrations of DS measured with a new chromogenic assay. The volume of distribution was approximately 1.8 times greater than the theoretical plasma volume and was independent of dose. In contrast, the clearance decreased with dose and the terminal half-life ranged from 0.45 +/- 0.08 hours at 0.5 mg/kg to 0.72 +/- 0.11 hours (mean +/- SD) at 2 mg/kg. The bioavailabilities of subcutaneous (SC) and intramuscular (IM) administration relative to those of intravenous administration were determined in 12 other volunteers. The respective bioavailabilities were 24.7% +/- 12.9% and 12.4% +/- 9.2% for SC and IM administration. There was no detectable change in the APTT and the TCT when the volunteers were injected with 1.5 mg/kg SC or IM. In addition, the pharmacokinetic parameters derived from plasma concentrations of DS showed considerable interindividual variations by the two later routes of administration. Peak concentrations were noted 2.7 +/- 1.3 hours after SC injection and 4.3 +/- 4.9 hours after IM injection. The average peak concentrations were 0.7 +/- 0.3 and 0.4 +/- 0.2 mg/L after SC and IM injections, respectively. The half-lives of DS were 7.9 +/- 6.5 hours (SC) and 6.3 +/- 7.4 hours (IM). No adverse reaction to DS was recorded during this study. .A Dol F; Houin G; Rostin M; Montastruc JL; Dupouy D; Gianese F; Sie P; Boneu B. .I 200477 .U 90001539 .S Blood 9001; 74(5):1583-90 .M Animal; Blood Coagulation/*; Cells, Cultured; Factor VII/*ME; Factor X/*ME; Factor Xa/*ME; Human; Kinetics; Lipopolysaccharides/PD; Macrophages/DE/*PH; Rabbits; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Initiation of the extrinsic pathway of coagulation by human and rabbit alveolar macrophages: a kinetic study. .P JOURNAL ARTICLE. .W We examined assembly and expression of the factor X activating complex on human and rabbit alveolar macrophages. Kinetic parameters of the factor X activating reaction were determined by functional titrations of factors VII and X with macrophage tissue factor (TF) added. We found rapid activation of factor X to Xa on alveolar macrophage surfaces. Detection of rapid factor Xa formation on macrophages required addition of exogenous factors VII and X. At plasma concentrations of the purified factors, factor Xa was formed on freshly isolated macrophages at approximately 5.4 pmol/min/10(6) cells. After macrophage maturation in culture for 20 hours with LPS (endotoxin) added, the factor X activation rate was increased two- to sixfold. The km' (apparent km) of TF-factor VII enzymatic complexes assembled on alveolar macrophages for factor X were (258 +/- 55 and 475 +/- 264 nmol/L for human and rabbit cells, respectively). The km' did not change during macrophage maturation in culture, but V'max (apparent Vmax) was consistently increased. The K1/2 of human factor VII (concentrations giving half maximal rates of factor X activation) for the interaction with human and rabbit alveolar macrophage TF were 0.191 +/- 0.096 and 1.7 +/- 0.7 etamol/L, respectively. The K1/2 were not significantly changed after maturation, whereas rates of Xa formation at saturation with factor VII were increased. The fast rates of factor X activation observed at physiologic concentrations of plasma-derived factors VII and X indicate that TF on alveolar macrophages is likely to provide sites for binding of factor VII and activation of factor X in vivo during clotting reactions associated with alveolar edema and inflammation. .A McGee MP; Wallin R; Wheeler FB; Rothberger H. .I 200478 .U 90001541 .S Blood 9001; 74(5):1600-2 .M Acute Disease; Autoantibodies/*AN; Autoimmune Diseases/*BL; Child; Chronic Disease; Human; Platelet Membrane Glycoproteins/*IM; Purpura, Thrombocytopenic/BL/*IM; Reference Values; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Autoantibodies against platelet membrane glycoproteins in children with acute and chronic immune thrombocytopenic purpura. .P JOURNAL ARTICLE. .W The autoimmune nature of chronic immune thrombocytopenic purpura (ITP) in adults is widely accepted. In contrast, the pathogenetic mechanism in acute and chronic ITP in children is not known. In this report, we studied 39 children with destructive thrombocytopenia, 15 patients with acute ITP and 24 patients with chronic ITP. Platelet autoantibodies to platelet glycoprotein IIb/IIIa were detected in 14 of 24 patients (58.3%) in the chronic ITP group and in four of 15 (26.7%) with acute ITP. Binding ratios (+/- SD) of positive patients were significantly greater (P = .01) in chronic ITP (8.0 +/- 9.1) when compared with those of acute ITP where the binding ratios were only slightly above the normal range (1.9 +/- 0.4). The results show that autoantibodies against platelet glycoproteins are present in the majority of children with chronic ITP confirming the autoimmune nature of this disorder. The minimal elevation seen in the positive children with acute ITP suggests a different pathogenetic mechanism. These data suggest that this approach may be useful in differentiating acute from chronic ITP patients. .A Berchtold P; McMillan R; Tani P; Sommerville-Nielsen S; Blanchette VS. .I 200479 .U 90001547 .S Blood 9001; 74(5):1644-50 .M Blotting, Northern; Cells, Cultured; Homeostasis; Human; Immunoblotting; In Vitro; Kinetics; Monocytes/*PH; Plasminogen Activators/*AI; Plasminogen Inactivators/AN/*ME; Radioimmunoassay; RNA, Messenger/AN/GE; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Thromboplastin/GE/*ME. .T Differential regulation of tissue factor and plasminogen activator inhibitor by human mononuclear cells. .P JOURNAL ARTICLE. .W Fibrin is a hallmark of immune-mediated tissue lesions. The presence of fibrin in such lesions implies both the formation of fibrin via coagulation and the accompanying restriction of fibrinolysis, allowing fibrin to persist. Previous work has shown that human monocytes exposed to an inflammatory stimulus such as lipopolysaccharide (LPS) produce both tissue factor (TF) and plasminogen activator inhibitor--type 2 (PAI-2). These two proteins favor fibrin deposition, and evidence implies that cellular production of these two molecules may be linked. Another proinflammatory process pertinent to immune-mediated tissue damage and fibrin deposition is the response to alloantigen. Peripheral-blood mononuclear cells (PBM), consisting of lymphocytes and monocytes together, responded to alloantigen stimulation with differential expression of TF and PAI-2. PBM exposed to alloantigen developed high levels of TF activity, with no concomitant increase in PAI-2 activity or antigen. Alloantigen-stimulated PBM did not accumulate intracellular PAI-2, nor did they degrade PAI-2 added to cultures. This lack of PAI-2 production was not due to inadequate stimulation, as tritiated thymidine uptake and TF production demonstrated recognition of, and a vigorous reaction to, alloantigen. The divergent TF and PAI-2 responses of PBM exposed to alloantigen was maintained over 5 days and was reflected by mRNA profiles. These results imply that under specific physiologically relevant conditions, the procoagulant and antifibrinolytic effectors of inflammatory mononuclear cells can be independently regulated. This would imply more flexibility to monocyte mechanisms that favor fibrin deposition than previously thought. .A Schwartz BS; Bradshaw JD. .I 200480 .U 90001548 .S Blood 9001; 74(5):1651-7 .M Antibodies, Monoclonal/*DU; Antigens, CD/*AN; Cell Differentiation; Cells, Cultured; Human; Interleukin-1/*PD; Interleukin-2/*PD; Interleukin-6/*PD; Kinetics; Leukemia, Prolymphocytic/*IM; Lymphocyte Transformation/*/DE; Microscopy, Electron; Recombinant Proteins/PD; Reference Values; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; T-Lymphocytes/DE/*IM/UL; Tetradecanoylphorbol Acetate/PD. .T Proliferative pathways in CD1- CD3+ CD4+ CD8+ T-prolymphocytic leukemic cells: analysis with monoclonal antibodies and cytokines. .P JOURNAL ARTICLE. .W The antigenic profile and the proliferative pathways in leukemic cells from the patient TRT with T-prolymphocytic leukemia (T-PLL) were analyzed using monoclonal antibodies (MoAbs) and cytokines. T-PLL cells expressed the phenotype CD1- CD3+ CD4+ CD8+. Incubation with the differentiating agent phorbol-12-myristate-13-acetate markedly increased the percentage of cells with the CD4- CD8+ phenotype, suggesting that leukemic cells were already committed towards a differentiated element with the CD4- CD8+ phenotype. T-PLL cells were induced to proliferate by anti-CD2 MoAb 9-1 + 9.6 and by anti-CD3 MoAb OKT3. The two pathways exhibited normal functional interactions and were susceptible to modulation by anti-HLA class I MoAbs. These results indicate that regulation of cell proliferation was preserved to a significant extent in the T-PLL cells analyzed. At variance with normal resting T cells that require previous activation to proliferate when incubated with interleukin-1 (IL-1) or interleukin-2 (IL-2), T-PLL cells proliferated vigorously when incubated with either interleukin. Furthermore, T-PLL cells proliferated when incubated with immune interferon (IFN-gamma). The latter finding parallels the enhancement by IFN-gamma of the proliferative response of lectin-activated murine T lymphocytes. These results suggest that T-PLL cells, which express a high constitutive level of c-myc mRNA, may be in an activated state. The antigenic phenotype and the characteristics of the proliferative pathways of T-PLL cells from the patient TRT are compatible with the possibility that they may be derived from an intermediate thymocyte. .A Turco MC; De Felice M; Alfinito F; Lamberti A; Costanzo F; Giordano M; Martinelli V; Rotoli B; Ferrone S; Venuta S. .I 200481 .U 90001549 .S Blood 9001; 74(5):1658-64 .M Blood Transfusion/AE; Enzyme-Linked Immunosorbent Assay; Ethnic Groups; Female; Genes, Viral; Human; HTLV-II/GE/*IP; HTLV-II Antibodies/AN; HTLV-II Infections/DI/*EP/ET; Male; New York City; Polymerase Chain Reaction; Prevalence; Risk Factors; Substance Abuse/CO; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Prevalence of human T-cell leukemia/lymphoma virus (HTLV) type II infection among high-risk individuals: type-specific identification of HTLVs by polymerase chain reaction. .P JOURNAL ARTICLE. .W The extent of human T-cell leukemia/lymphoma virus type II (HTLV-II) infection and its rate of spread have been difficult to determine owing to the serological cross-reactivity between HTLV-I and HTLV-II. The present study overcame this problem by directly detecting type-specific proviral sequences by means of the polymerase chain reaction (PCR) and liquid hybridization. Screening was performed on a cohort of primarily white intravenous drug abusers (IVDAs), and individuals of other behaviorally defined risk groups from the New York City area. Eleven percent (19 of 169) of the individuals in these high-risk groups were determined by PCR to have HTLV-II proviral infections. One of these patients displayed an exfoliative erythrodermatitis. Thirteen of the 19 subjects were positive in an HTLV-II enzyme-linked immunosorbent assay (ELISA). The remaining six individuals, although negative in the HTLV-II ELISA, were confirmed as HTLV-II positive by analyzing their DNA with a second HTLV-II-specific primer detector system. Four additional individuals were reactive in the HTLV-II ELISA but were PCR-negative for HTLV-II. PCR analysis for HTLV-I revealed that all four were positive for that virus. Thirty-seven percent (seven of 19) of the HTLV-II PCR-positive subjects were also PCR-positive for HTLV-I, and 84% (16 of 19) of the HTLV-II positive individuals were infected with human immunodeficiency virus (HIV-1). Six individuals were triply infected with HTLV-I, HTLV-II, and HIV-1. .A Ehrlich GD; Glaser JB; LaVigne K; Quan D; Mildvan D; Sninsky JJ; Kwok S; Papsidero L; Poiesz BJ. .I 200482 .U 90001553 .S Blood 9001; 74(5):1690-7 .M Antigens, CD/AN; Bone Marrow/*IM; Cells, Cultured; Child; Cytotoxicity, Immunologic; Human; HLA Antigens/AN; Interleukin-2/PD; Killer Cells, Lymphokine-Activated/DE/*IM; Kinetics; Leukemia, Lymphocytic, Acute/*IM; Leukemia, Nonlymphocytic, Acute/*IM; Recombinant Proteins/PD. .T Interleukin-2 induction of lymphokine-activated killer (LAK) activity in the peripheral blood and bone marrow of acute leukemia patients: II. Feasibility of LAK generation in children with active disease and in remission. .P JOURNAL ARTICLE. .W Activation and expansion in culture with rIL-2 of peripheral blood (PB) and/or bone marrow (BM) specimens derived from children with ALL and ANLL, with active disease (AP) and in remission were studied (RP). Baseline NK cytolytic activity from AP was found to be depressed, whereas RP-derived cells had normal NK activity, as assayed against K562 targets. Culture in rIL-2 significantly enhanced the NK activity of both AP- and RP-derived cells and generated LAK activity, as assayed by 4-hour 51Cr release, against NK-resistant Raji cell line and against fresh, allogeneic, and autologous tumor cells. Lytic activity against fresh, cryopreserved leukemia blasts was of lower than that found against cell lines. In three patients higher lytic activity against autologous than against allogeneic blasts was demonstrated. Expansion in culture with rIL-2 varied from twofold to 120-fold. rIL-2 activation and expansion was better in RP than in AP. The predominant phenotype of activated cells, as determined by flow cytometry, was [mean % (SD)]: CD3- = 54 (12), CD8+ = 55 (17), and NKH1+ = 26 (7). The consistently high level of CD8+ cells was accompanied by very low levels of CD4+ cells: mean = 11% (14). Double-marker analysis showed mean of 33% (10) for CD3+/NKH1+ cells and mean = 32 (11) for CD8+/NKH1+ cells, implying that these populations were overlapping. Kinetics of expression of cell surface markers during 2 to 3 weeks in culture showed that CD8+ and NKH1+ enrichment occurred during the first week and lasted for up to 4 weeks, whereas CD4+ expression decreased after the second week. A significant decrease in the expression of IL-2 receptors (CD25) was observed from the second week of culture. This study shows the feasibility of in vitro generation of killer cells from PB and BM of pediatric leukemia patients. .A Adler A; Albo V; Blatt J; Whiteside TL; Herberman RB. .I 200483 .U 90001555 .S Blood 9001; 74(5):1704-10 .M Bacterial Infections/BL/*IM/PP; Blood Pressure; Complement 3a/AN; Complement 4a/AN; Heart Rate; Human; Interleukin-6/*BL; Shock, Septic/BL/IM/PP. .T Increased plasma levels of interleukin-6 in sepsis [see comments] .P JOURNAL ARTICLE. .W Interleukin-6 (IL-6) is likely to be an important mediator of the inflammatory response. We measured levels of this cytokine in plasma samples from 37 patients with sepsis or septic shock obtained at the time of admission to the intensive care unit and related these levels to hemodynamic and biochemical parameters as well as to clinical outcome. In 32 of the 37 patients, increased levels of IL-6 were found, occasionally up to 7,500 times the normal level. The highest IL-6 levels were encountered in patients who suffered from septic shock (P value of the difference between patients with and without shock less than .0001). In addition, IL-6 significantly correlated with plasma lactate (P less than .0001), heart rate (P = .05) and, inversely, with mean arterial pressure (P = .01) and platelet counts (P = .0002). Significant correlations of IL-6 with the anaphylatoxins C3a (P = .0001) and C4a (P = .0002) and with the main inhibitor of the classical pathway of complement, C1-inhibitor (inverse correlation, P = .05), were also observed. IL-6 on admission appeared to be of prognostic significance: levels were higher in septic patients who subsequently died than in those who survived (P = .0003), in particular when only patients with septic shock were considered (P less than .0001). All nine septic patients with levels of less than 40 U/mL on admission survived, whereas 89% of the nine patients with levels exceeding 7,500 U/mL died. These data provide evidence for a role of IL-6 in the pathophysiology of septic shock. Further studies are needed to reveal whether IL-6 in sepsis is directly involved in mediating lethal complications or whether it is to be considered as an "alarm hormone" that reflects endothelial cell injury probably mediated by the anaphylatoxines. .A Hack CE; De Groot ER; Felt-Bersma RJ; Nuijens JH; Strack Van Schijndel RJ; Eerenberg-Belmer AJ; Thijs LG; Aarden LA. .I 200484 .U 90001556 .S Blood 9001; 74(5):1711-7 .M Animal; B-Lymphocytes/*CY/DE; Bone Marrow/*CY/DE; Cell Differentiation/DE; Cell Survival/DE; Cells, Cultured; Hematopoiesis/DE; Hematopoietic Stem Cells/*CY/DE; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Mice, Inbred C57BL; Neutrophils/CY/DE; Support, U.S. Gov't, P.H.S.; Transforming Growth Factors/*PD. .T Differential effects of TGF-beta 1 on lymphohemopoiesis in long-term bone marrow cultures. .P JOURNAL ARTICLE. .W Latent transforming growth factors beta (TGF-beta) are easily detectable in embryonic and adult hematopoietic tissues and in vitro studies show that they are potent antagonists of lymphopoiesis and myelopoiesis when converted to biologically active form. To learn more about possible roles in hematopoiesis, active TGF-beta 1 was added to cultures prepared to support myeloid cells (Dexter conditions) or B lineage lymphocytes (Whitlock-Witte conditions) and studied in detail. Hematopoiesis was permanently arrested in Dexter cultures treated with 40 pmol/L (1 ng/mL) of active TGF-beta from initiation. In addition, adipogenesis was inhibited in a dose-dependent manner, and adherent layers from treated cultures were defective when recharged with fresh bone marrow cells. Ongoing neutrophil production was terminated in established cultures when addition of the factor was delayed for 8 weeks. In contrast, in experiments with Whitlock-Witte cultures, some of the flasks produced lymphocytes in the continuous presence of TGF-beta 1 (40 pmol/L). Lymphopoiesis was completely arrested by ten-fold higher concentrations, and this was most effective when added at the beginning of culture. Precursors of lymphocytes as well as the microenvironmental elements necessary for supporting their growth survived 2 weeks of cytokine treatment (400 pmol/L) in Dexter cultures. Normal outgrowth of lymphocytes occurred when the cultures were switched to Whitlock-Witte conditions. Surface marker expression on lymphocytes growing in TGF-beta resistant or previously treated cultures was not unusual. These studies demonstrate that TGF-beta is a negative regulator of hematopoiesis in long-term cultures and show that this includes effects on microenvironmental elements. At low concentrations, production of myeloid cells was preferentially affected. .A Hayashi S; Gimble JM; Henley A; Ellingsworth LR; Kincade PW. .I 200485 .U 90001557 .S Blood 9001; 74(5):1718-22 .M Blood Proteins/*BI/SE; Bone Marrow/DE/IM/PA; Cells, Cultured; DNA Replication; Human; Immunoglobulins/BI/GE; Interferon Type I/*PD; Kinetics; Multiple Myeloma/*IM/PA; RNA, Messenger/GE; Support, Non-U.S. Gov't; Transcription, Genetic. .T Sensitive inhibitory effect of interferon-alpha on M-protein secretion of human myeloma cells. .P JOURNAL ARTICLE. .W The effects of interferon-alpha (IFN alpha) on in vitro proliferation and M-protein secretion in human myeloma cells were investigated. Human myeloma cells were purified from bone marrow aspirates in 12 multiple myeloma patients. Purified myeloma cells were cultured for 48 hours with IFN alpha at its lower concentrations (0.1 to 100 U/mL). The cells were then pulsed with 3H-TdR for the last 12 hours and 3H-TdR uptake was measured (in vitro proliferation). After 48-hour culture, supernatants were harvested and the amount of M-protein in these fluids were measured by enzyme-linked immunosorbent assay (ELISA) (in vitro M-protein secretion). In vitro M-protein secretions of myeloma cells were significantly suppressed even at 0.1 U/mL of IFN alpha, while 3H-TdR uptakes were not so suppressed until 10 or 100 U/mL of IFN alpha were added. The expressions of secretory immunoglobulin (Ig) mRNA of these myeloma cells were also selectively suppressed by IFN alpha. Furthermore, after IFN alpha had been administered intramuscularly, 3 to 6 x 10(6) U/d for at least 1 month, in vitro M-protein secretions of these myeloma cells were decreased compared with those before IFN alpha administration. Therefore, these results suggest that IFN alpha has more sensitive inhibitory effect on M-protein secretion of human myeloma cells rather than on myeloma cell proliferation. .A Tanaka H; Tanabe O; Iwato K; Asaoku H; Ishikawa H; Nobuyoshi M; Kawano M; Kuramoto A. .I 200486 .U 90001558 .S Blood 9001; 74(5):1723-7 .M Cell Line; Cell Survival/DE; Clone Cells; Doxorubicin/PD; Drug Resistance; Human; Leukemia, T-Cell; Membrane Glycoproteins/BI/GE; Multiple Myeloma; Mutation; Recombinant Proteins/PD; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Transcription, Genetic/DE; Tumor Cells, Cultured/*CY/DE; Tumor Necrosis Factor/*PD; Vinblastine/PD. .T Effects of tumor necrosis factor on sensitive and multidrug resistant human leukemia and myeloma cell lines. .P JOURNAL ARTICLE. .W Two human tumor cell lines exhibiting acquired multidrug resistance (MDR) with increased expression of a cell surface glycoprotein (GP-170) were tested for their sensitivity to human recombinant tumor necrosis factor (rTNF). The drug resistant mutant lines (CEM/V, a T-cell leukemia line resistant to vinblastine, and 8226/D, a multiple myeloma line resistant to doxorubicin), were markedly more sensitive to rTNF in clonogenic assay than were their drug-sensitive parental lines (CEM, 8226). As determined by radioreceptor assay, the number of cell surface receptors for rTNF did not differ on the parental and drug-resistant lines. During the first 24 hours after addition of rTNF, there was a decrease in intracellular ATP content in the CEM/V line but not in the CEM line. No differential effect of rTNF on ATP content was observed between 8226 and 8226/D. As determined by RNA dot-blot analysis, total cellular RNA for GP-170 was increased in the 8226/D cells. After rTNF exposure, expression of total cellular RNA for GP-170 was not altered. Accumulation of radiolabeled doxorubicin by 8226/D cells was not altered by previous or coincubation with rTNF. These findings suggest that the effects of rTNF on MDR cells is not related to TNF receptor number and is mediated at a step subsequent to rTNF binding and not by either inhibition of synthesis of GP-170 or by alteration in the function of the GP-170 efflux pump. .A Salmon SE; Soehnlen B; Dalton WS; Meltzer P; Scuderi P. .I 200487 .U 90001559 .S Blood 9001; 74(5):1728-37 .M Antibiotics, Antineoplastic/*PD; Cell Differentiation/*DE; Cell Division/DE; Cell Line; Cells, Cultured; Dose-Response Relationship, Drug; Human; Isoxazoles/*PD; Kinetics; Leukemia, Myeloid; Leukemia, Nonlymphocytic, Acute/*BL; Leukemia, Promyelocytic, Acute; Leukocytes/*CY/DE/PA; Oxazoles/*PD; Reference Values; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured/*CY/DE. .T Monocytoid differentiation of freshly isolated human myeloid leukemia cells and HL-60 cells induced by the glutamine antagonist acivicin. .P JOURNAL ARTICLE. .W Previously we showed that starvation of HL-60 promyelocytic leukemia cells for a single essential amino acid induced irreversible differentiation into more mature monocyte-like cells. Although not an essential amino acid, glutamine is important in the growth of normal and neoplastic cells. The glutamine analogue, alpha S,5S-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (acivicin) inhibits several glutamine-utilizing enzymes and therefore depletes cells of certain metabolic end products. The current study was designed to examine in vitro the effects of acivicin on growth and differentiation of several established human myeloid leukemia cell lines, including the HL-60 cell line, and of freshly isolated cells from patients with acute nonlymphocytic leukemia (ANLL). Four-day culture of HL-60 cells with acivicin at concentrations of 0.1 to 10.0 micrograms/mL (0.56 to 56 nmol/L) decreased cell growth by 33% to 88% as compared with untreated control cells. Viability of cells was greater than 92% for untreated cells and 93% to 41% for acivicin-treated cells. Cells treated with acivicin differentiated along a monocytic pathway as shown by increased H2O2 production and alpha-naphthyl butyrate esterase (NSE) content. Differentiation was time and dose dependent, and was irreversible. Changes in H2O2 production and NSE content were partially abrogated by co-culture with 10 mmol/L exogenous cytidine and guanosine but not by co-culture with other nucleosides or glutamine. At these concentrations of acivicin, differentiation was associated with expression of the N-formyl-methyl-leucyl-phenylalanine-receptor (FMLP-R) on 8% to 29% of cells as compared with 8% for control cells. Acivicin potentiated the differentiating effects of interferon-gamma, tumor necrosis factor, dihydroxyvitamin D3, dimethylsulfoxide, and retinoic acid. Culture of cells from the U937 (monoblastic), K562 (erythroleukemia), and KG-1 (myeloblastic) cell lines resulted in decreased growth and viability, but not consistently in differentiation. Acivicin decreased survival of freshly isolated ANLL cells and increased their H2O2 production and NSE content. These results suggest that the glutamine analogue acivicin may be useful as a differentiating agent with antileukemia activity in patients with ANLL. .A Nichols KE; Chitneni SR; Moore JO; Weinberg JB. .I 200488 .U 90001560 .S Blood 9001; 74(5):1738-46 .M Acute Disease; Antigens, CD/*AN; Blotting, Northern; Blotting, Southern; Child; Child, Preschool; DNA, Neoplasm/*GE; Female; Gene Rearrangement, T-Lymphocyte/*; Genes, Immunoglobulin/*; Human; Infant; Leukemia/CL/*GE/IM; Leukemia, Lymphocytic, Acute/CL/GE/IM; Male; Monocytes/AN; Nucleic Acid Hybridization; Phenotype; Receptors, Antigen, T-Cell/GE; Restriction Mapping; RNA, Neoplasm/*GE; Support, Non-U.S. Gov't. .T Molecular analysis of acute undifferentiated leukemia: two distinct subgroups at the DNA and RNA levels. .P JOURNAL ARTICLE. .W On the basis of negativity for myeloperoxidase (MPO) and absence of lineage-associated antigens on the cell surface, 11 children were diagnosed as having acute undifferentiated leukemia. To analyze the molecular events associated with hematopoietic cell differentiation, we analyzed the configuration of the immunoglobulin (Ig) and T-cell receptor (TCR) delta, alpha, gamma, and beta genes in these patients. In parallel, transcription of the genes for MPO, terminal deoxynucleotidyltransferase (TdT), CD3-gamma, Ig-mu, TCR-gamma, and beta was also examined. Six patients showed rearrangements of both the Ig heavy (H) and TCR-delta genes, frequently accompanied with Ig-kappa, TCR-alpha, gamma, and beta gene rearrangements. These findings indicated that the leukemic cells from the six patients had been committed to the lymphoid lineage. This concept was supported by the presence of TdT transcripts in three analyzed specimens from these patients. In contrast, the remaining five patients did not display rearrangements of the Ig or TCR genes, and TdT transcripts were undetectable in two patients tested. MPO transcripts were not detected in four patients analyzed, thus providing no evidence of myeloid differentiation. After hybridization with the CD3-gamma gene, three of six patients showed transcription of the CD3-gamma gene. In addition to CD3-gamma transcripts, one patient with rearrangements of the Ig-H, TCR-delta, alpha, gamma, and beta genes also had full-length TCR-beta and gamma transcripts, indicating a T-precursor-cell origin of the leukemic cells from this patient. The Ig and TCR genes were in the germline configuration in the other two patients with CD3-gamma transcripts. One of them did not express the CD7 antigen but did express the CD33 antigen on the cell surface, suggesting that CD3-gamma transcription may not always be an event restricted to cells differentiating along the T-cell lineage. .A Hara J; Yumura-Yagi K; Tawa A; Ishihara S; Murata M; Terada N; Izumi Y; Champagne E; Takihara Y; Mak TW; et al. .I 200489 .U 90001562 .S Blood 9001; 74(5):1758-61 .M Acute Disease; Adult; Aged; Antineoplastic Agents/TU; Antineoplastic Agents, Combined/TU; Blast Crisis/*PA; Bone Marrow/*PA; Case Report; Female; Human; Leukemia/DT/*PA; Leukocyte Count; Male; Middle Age; Myelodysplastic Syndromes/PA. .T Peripheral acute leukemia: high peripheral but low-marrow blast count. .P JOURNAL ARTICLE. .W We report five patients who had greater than 30% peripheral blasts and less than 30% marrow blasts. By the current standards these cases would be classified as myelodysplastic syndrome. Four of five patients progressed to acute leukemia within approximately 1 1/2 months of developing greater than 30% peripheral blasts. Two of these four patients had evidence of acute leukemia by criteria other than marrow involvement at the time of presentation: one patient had evidence of multifocal dermal involvement; and the other patient had a cytogenetic abnormality, t(8;21), found predominantly in acute leukemia. The fifth patient developed acute leukemia 2 years after initial presentation with greater than 30% peripheral blasts. Although our series of patients is small, it does suggest that patients who have greater than 30% peripheral blasts should be considered an acute leukemia, even with less than 30% marrow blasts. .A Cason JD; Trujillo JM; Estey EH; Huh YO; Freireich EJ; Stass SA. .I 200490 .U 90001565 .S Blood 9001; 74(5):1774-80 .M Bone Marrow/PA; Calcium/BL; Female; Hemoglobins/AN; Human; IgG/AN; Male; Multiple Myeloma/BL/MO/*PA; Neoplasm Staging; Platelet Count; Prognosis; Serum Albumin/AN; Support, Non-U.S. Gov't. .T Prognostic variables and clinical staging in multiple myeloma. .P JOURNAL ARTICLE. .W To evaluate the most important factors in the prognosis and staging of multiple myeloma (MM), the presenting clinical features of 163 previously untreated patients with MM were correlated with survival duration using univariate and multivariate regression analyses. The univariate proportional hazard analysis ranked the parameters in the following order of importance: platelet count, hemoglobin level (Hb), tumor cell mass stage, lytic bone lesions, creatinine, and age. When the individual contribution of each variable was assessed by multivariate regression analysis, platelet count was confirmed to be the dominant feature for prognosis and clinical stage provided additional information. The introduction of platelet count could then be used to improve the reliability of the Durie and Salmon staging, by allowing to separate the high-risk group (stages II and III) into a smaller subgroup (22%) of thrombocytopenic patients (less than 150 x 10(9) platelets/L) whose risk of death was actually very high (median survival, 9 months) and a larger subgroup (46%) of patients with normal platelet count and intermediate or standard risk (median survival, 48 months). This simple change in the prognostic system gave rise to markedly different survival curves also after the exclusion of patients with renal failure and applied successfully to both old and young patients (greater than and less than 50 years, respectively). Finally, platelet count, Hb, and lytic bone lesions could be combined simply to stratify patients with normal renal function into three risk groups: (1) low (39% of cases; median survival, 79 months), (2) intermediate (53% of cases; median survival, 48 months), and (3) high (8% of cases; median survival, 19 months). .A Cavo M; Galieni P; Zuffa E; Baccarani M; Gobbi M; Tura S. .I 200491 .U 90001566 .S Blood 9001; 74(5):1781-90 .M Adolescence; Adult; Aged; Antigens, CD/AN; Bone Marrow/*PA; Child; Child, Preschool; Chromosome Abnormalities; Female; Hematopoietic Stem Cells/*PA; Human; Karyotyping; Leukemia, Megakaryocytic, Acute/GE/*PA; Leukemia, Nonlymphocytic, Acute/GE/PA; Male; Middle Age; Phenotype; Retrospective Studies; Support, Non-U.S. Gov't. .T Multipotent stem cell involvement in megakaryoblastic leukemia: cytologic and cytogenetic evidence in 15 patients. .P JOURNAL ARTICLE. .W Cytologic and cytogenetic results obtained from patients fulfilling the FAB criteria for the diagnosis of acute nonlymphocytic leukemia (ANLL) of megakaryocytic lineage (ANLL-M7) are reported. Eleven cases were de novo ANLL-M7, of whom three presented with acute myelofibrosis. Four cases were megakaryoblastic transformations of chronic myelogenous leukemia (two cases), refractory anemia with excess of blasts (one case), and polycythemia vera (one case). Four patients showed a minority of granular blasts, with occasional Auer rods in one. Positive myeloperoxidase and/or sudan black-B stainings and CD13 positivity in these cases were consistent with the presence of a myeloid involvement. Morphologic evidence of associated myelodysplastic features was detected in all evaluable patients with de novo ANLL-M7. These cytologic findings indicate that ANLL-M7 may frequently represent a multilineage proliferation. Cytogenetic studies revealed -7/7q- and +8, alone or in combination with additional aberrations, in three cases each. Rearrangements involving bands 3q21 or 3q26 were seen in two patients and +21, as an additional aberration, in one. Other structural rearrangements all observed in a single patient were inv(16)(p13q22) at megakaryoblastic relapse with bone marrow eosinophilia, t(13;20)(q13 or 14;q11), del(20)(q11), and der(7)t(7;17)(p14;q22). Most breakpoints of these aberrations are located at bands frequently rearranged in malignant myeloid stem cell disorders. A review of 31 cases of the literature showed a frequent occurrence of -7/7q- and -5/5q- in ANLL-M7. Many of the chromosome aberrations so far described in ANLL-M7 appear to be shared by a spectrum of myeloid neoplasias and may be related to mechanisms conferring proliferative advantage to undifferentiated stem cells. .A Cuneo A; Mecucci C; Kerim S; Vandenberghe E; Dal Cin P; Van Orshoven A; Rodhain J; Bosly A; Michaux JL; Martiat P; et al. .I 200492 .U 90001569 .S Blood 9001; 74(5):1801-6 .M Base Sequence; Cell Line; Chromosomes, Human, Pair 11/*; Chromosomes, Human, Pair 14/*; DNA, Neoplasm/GE; Genes, Immunoglobulin/*; Genomic Library; Human; Immunoglobulins, Surface/*GE; Leukemia, B-Cell, Chronic/*GE/IM; Molecular Sequence Data; Restriction Mapping; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Translocation (Genetics)/*. .T An additional breakpoint region in the BCL-1 locus associated with the t(11;14)(q13;q32) translocation of B-lymphocytic malignancy. .P JOURNAL ARTICLE. .W The t(11;14)(q13;q32) translocation is associated with human B-lymphocytic malignancy. This translocation divides the IgH locus on chromosome 14q32 and may activate a postulated proto-oncogene, bcl-1, located on chromosome 11q13. Two samples of chronic lymphocytic leukemia with the t(11;14)(q32;q13) translocation were studied. The break in one sample was shown to join Jh sequences with the previously described bcl-1 major translocation cluster. DNA blots of the second sample suggested that Jh sequences were joined to a different breakpoint region on chromosome 11. This translocation was cloned and found to link the human Jh3 region and a new breakpoint region 63 kb telomeric of the major translocation cluster. This translocation occurred in part as the result of an aberrant D-J recombination. Recurrent translocations human B-lymphocytic malignancy. The definition of a new breakpoint region may aid the identification of the postulated bcl-1 gene. .A Meeker TC; Grimaldi JC; O'Rourke R; Louie E; Juliusson G; Einhorn S. .I 200493 .U 90001570 .S Blood 9001; 74(5):1807-10 .M Cell Differentiation/DE; Cell Line; Diglycerides/PD; Gene Expression/*; Genes, Structural/*; Human; Kinetics; Leukemia, Erythroblastic, Acute; Leukemia, Promyelocytic, Acute; Macrophages/CY/EN; Monocytes; RNA, Messenger/*GE; Superoxide Dismutase/*GE; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tetradecanoylphorbol Acetate/PD; Transcription, Genetic/*DE. .T Loss of copper-zinc superoxide dismutase gene expression in differentiated cells of myelo-monocytic origin. .P JOURNAL ARTICLE. .W Changes in the production of reactive oxygen species and total superoxide dismutase activity have been observed during differentiation of some hematopoietic cells. We therefore investigated whether the steady-state level and rate of transcription of superoxide dismutase-1 (SOD-1) mRNA change during terminal differentiation of the human leukemia cell lines THP-1, HEL, and HL-60 into macrophages and/or granulocytes, respectively. Macrophage differentiation is accompanied by a gradual decrease in both the transcription rate (10x) and the steady-state level (6x) of SOD-1 mRNA. No decrease was observed after treatment with the diacylglycerol analog 1,2 dioctanol-rac-glycerol (di-C8), which like phorbol 12-myristate 13-acetate also activates protein kinase C but does not induce differentiation at the concentration used. The same decrease in SOD-1 mRNA level was observed when HL-60 cells were induced to differentiate into granulocytes by treatment with dimethylsulfoxide. These data suggest that a decrease in SOD-1 mRNA to almost undetectable levels accompanies differentiation of macrophages and granulocytes. .A Auwerx JH; Chait A; Wolfbauer G; Deeb SS. .I 200494 .U 90001572 .S Blood 9001; 74(5):1817-22 .M Anemia, Sickle Cell/CO/*GE; Base Sequence; Case Report; Cloning, Molecular; DNA/BL/GE; Female; Genes, Reiterated/*; Genes, Structural; Globin/*GE; Haplotypes; Hemoglobin, Sickle/*GE; Heterozygote Detection; Human; Molecular Sequence Data; Mutation/*; Nucleotide Mapping; Promoter Regions (Genetics)/*; Restriction Mapping; RNA, Messenger/GE; Support, Non-U.S. Gov't; Thalassemia/CO/*GE. .T Beta+-thalassemia in cis of a sickle cell gene: occurrence of a promoter mutation on a beta s chromosome. .P JOURNAL ARTICLE. .W An atypical sickle cell trait with a very low level of hemoglobin S and features of heterozygous beta-thalassemia was recently described. In vitro globin chain synthesis strongly suggested the presence of the two abnormalities on the same chromosome. We report the corresponding beta S-thal gene. DNA sequence revealed a C----T base substitution in the distal promoter element CACCC, at position-88 from the cap site, in addition to the expected GAG----GTG mutation responsible for the structural variant (beta 6 Glu----Val). Reticulocyte mRNA titration and transient assay of the mutant gene in COS cells showed a defect in beta-mRNA production. Restriction haplotype and DNA sequence analyses revealed that the doubly mutated gene is associated with haplotype 19 (or Benin/Algeria haplotype). In particular, we found the (AT)9(T)4 repeated sequences specifically encountered 5' to the beta S gene of Benin Algeria type. These results support the view that the beta S-thal gene resulted from an independent thalassemic mutation having occurred on a beta S chromosome rather than (a) from a beta S mutation having altered a beta-thalassemic gene or (b) from a recombination event between two chromosomes, each carrying one of the mutations. .A Baklouti F; Ouazana R; Gonnet C; Lapillonne A; Delaunay J; Godet J. .I 200495 .U 90001573 .S Blood 9001; 74(5):1823-5 .M Crystallization; Hemoglobin C/*IP; Hemoglobin, Sickle/*; Human; Kinetics; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Time Factors. .T Acceleration of hemoglobin C crystallization by hemoglobin S. .P JOURNAL ARTICLE. .W We previously reported that circulating hemoglobin (Hb) CC erythrocytes contain oxygenated HbC crystals with little or no HbF and that HbF inhibits in vitro crystallization of HbC. We now report that HbS accelerates in vitro crystallization of HbC. Crystals were formed in 1.8 mol/L potassium phosphate buffer, pH 7.4, at 30 degrees C and were counted in several time intervals with a hematocytometer. The hemoglobin composition of Millipore-isolated crystals and supernatant were also analyzed. Under the conditions selected, 100% HbS formed needle-shaped crystals only after two hours. Pure HbC does not form crystals within 15 minutes, whereas a ratio of 10% HbS:90% HbC forms 1,100 crystals/mm3, 20% HbS:80% HbC forms 370 crystals/mm3, and 30% HbS:70% HbC forms 5 crystals/mm3. Crystals formed in the presence of HbS are tetragonal, as are pure HbC crystals. As compared with 100% HbC, HbA or albumin mixed with HbC showed a decreased number of crystals as a result of dilution. Analysis of the Hb content of isolated crystals by citrate agar gel electrophoresis showed that HbS was rapidly incorporated into the crystal in the same ratio over time. These results demonstrate that HbS accelerates crystallization of HbC with respect to the rates of crystallization of any of these two Hbs separately, through a mechanism that involves cocrystallization. These results may be significant in understanding SC disease. .A Lin MJ; Nagel RL; Hirsch RE. .I 200496 .U 90001574 .S Blood 9001; 74(5):1826-35 .M Acanthocytes/DE/*UL; Blood Groups/*GE; Chlorpromazine/PD; Erythrocytes, Abnormal/*UL; Human; Kell Blood-Group System/*GE; Kinetics; Microscopy, Electron, Scanning; Phosphatidylserines/*PD; Reference Values; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Effect of phosphatidylserine on the shape of McLeod red cell acanthocytes. .P JOURNAL ARTICLE. .W The rare McLeod blood group phenotype is characterized by weak Kell antigens, lack of the common Kx antigen, and acanthocytic morphology. Previous studies that did not detect membrane or cytoskeletal protein abnormalities suggested a lipid disturbance. In normal red cells, dimyristoyl phosphatidylserine (DMPS) is transported across the membrane by an enzymatic process and accumulates in the inner leaflet of the membrane bilayer causing discocyte to stomatocyte shape changes. Scanning electron microscopy of McLeod red cells shows a mixture comprised of 15% discocytes, 51% with irregular surfaces, and 34% acanthocytes. On incubation with various concentrations of DMPS at 37 degrees C for periods up to two hours, McLeod red cells transported DMPS across the membrane and caused irregularly shaped and acanthocytic McLeod red cells to attain normal discocyte shape and later to become stomatocytes. Chlorpromazine, which at 0 degrees C preferentially partitions into the inner monolayer of the membrane, had a similar effect on the shape of McLeod red cells. This suggests that in McLeod cells acanthocytosis is due to a lack of lipid in the inner leaflet of the membrane bilayer but that the imbalance is not caused by defective transport of phosphatidylserine across the membrane. .A Redman CM; Huima T; Robbins E; Lee S; Marsh WL. .I 200497 .U 90001576 .S Blood 9001; 74(5):1844-51 .M Acetylcholinesterase/BL; Animal; Erythrocyte Membrane/*PH/UL; Hydrolases/BL; Lysosomes/EN; Microscopy, Electron; Molecular Weight; Receptors, Transferrin/IP/*PH; Reticulocytes/*PH/UL; Sheep; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Reticulocyte maturation and exosome release: transferrin receptor containing exosomes shows multiple plasma membrane functions. .P JOURNAL ARTICLE. .W Vesicles (exosomes) released during sheep reticulocyte maturation contain a number of plasma membrane functions. Using an antibody coated, magnetic core bead, it has been shown unequivocally that vesicles that contain the transferrin receptor also contain other plasma membrane activities, such as the nucleoside transporter and acetylcholinesterase. Lysosomal activities, normally found in the same pellet, are excluded from the transferrin receptor-containing exosomes, suggesting that there is a common mechanism to segregate and externalize specific plasma membrane proteins. In addition to the sheep, electron micrographic studies show that exosomes can be retrieved from the circulation of anemic pigs, rats, and rabbits. .A Johnstone RM; Bianchini A; Teng K. .I 200498 .U 90001577 .S Blood 9001; 74(5):1852-7 .M Adolescence; Anemia, Aplastic/*SU; Bone Marrow Transplantation/*; Child; Child, Preschool; Female; Histocompatibility Testing; Human; HLA Antigens/AN; Infant; Leukocyte Culture Test, Mixed; Male; Support, Non-U.S. Gov't; Tissue Donors. .T Bone marrow transplantation for children with severe aplastic anemia: use of donors other than HLA-identical siblings. .P JOURNAL ARTICLE. .W Eighty-five percent of untransfused and 70% of transfused patients with severe aplastic anemia (SAA) are cured with bone marrow transplants from histocompatible sibling donors. Use of partially matched family donors or unrelated donors has been relatively unsuccessful because of high incidences of graft rejection and graft-versus-host disease (GVHD). Thirteen children with SAA received marrow grafts from alternative donors (sibling 4, parent 5, unrelated 4). The first three patients were pretreated with cyclophosphamide (CYCLO) +/- irradiation and received methotrexate for GVHD prophylaxis. Subsequent children were pretreated with CYCLO + high-dose cytosine arabinoside + methylprednisolone + total body irradiation, had monoclonal antibody T-cell depletion of the donor marrow, and received cyclosporine for GVHD prophylaxis. Three heavily transfused patients with haploidentical-related donors failed to engraft and died. All 10 patients with more closely matched donors engrafted. Acute GVHD was grade II in only one patient (non-T-depleted); this patient is the only one with severe chronic GVHD. Three engrafted patients died (Pneumocystis pneumonia, systemic parainfluenza, venocclusive disease). Seven children are alive 33+ to 2,692+ days. Donors for the survivors were siblings 3, parent 1, unrelated 3. These data suggest that bone marrow transplantation from closely matched donors other than histocompatible siblings can be effective therapy for SAA if an intensive conditioning regimen is used. These results must be confirmed with larger numbers and longer follow-up. .A Camitta B; Ash R; Menitove J; Murray K; Lawton C; Hunter J; Casper J. .I 200499 .U 90001578 .S Blood 9001; 74(5):1858 .M Antineoplastic Agents/AD/TU; Antineoplastic Agents, Combined/*TU; Cytarabine/*TU; Human; Leukemia, Promyelocytic, Acute/*DT. .T Treatment of acute promyelocytic leukemia [letter] .P LETTER. .A Arlin ZA; Feldman EJ. .I 200500 .U 90001579 .S Blood 9001; 74(5):1858-9 .M Adult; Age Factors; Human; Leukemia, Myeloid, Chronic/*DI/EP; Middle Age. .T Age at diagnosis of chronic myelogenous leukemia [letter; comment] .P COMMENT; LETTER. .A Juneja SK; Januszewicz EH. .I 200501 .U 90001580 .S Blood 9001; 74(5):1859-60 .M von Willebrand's Disease/*DT; Bleeding Time; Case Report; Desmopressin/AD/*TU; Female; Human; Infusions, Intravenous; Middle Age; Platelet Count. .T DDAVP for type IIB von Willebrand disease [letter] .P LETTER. .A Fowler WE; Berkowitz LR; Roberts HR. .I 200502 .U 90001581 .S Blood 9001; 74(5):1860-1 .M Erythrocytes/EN; Evolution/*; Glucosephosphate Dehydrogenase/BL/*GE; Glucosephosphate Dehydrogenase Deficiency/GE; Human; Mutation; Variation (Genetics)/*. .T Evolution of glucose-6-phosphate dehydrogenase variants A+ and A- [letter; comment] .P COMMENT; LETTER. .A Yoshida A. .I 200503 .U 90002055 .S Br J Rheumatol 9001; 28(5):369-71 .M Animal; Arthritis/*/IM/PC/TH; Heat; Heat-Shock Proteins/*/GE/IM; Human; Stress/CO. .T Heat-shock proteins and arthritis. .P JOURNAL ARTICLE. .A Bernstein RM. .I 200504 .U 90002056 .S Br J Rheumatol 9001; 28(5):371-3 .M Human; Reflex Sympathetic Dystrophy/*DI/TH. .T Algodystrophy. .P JOURNAL ARTICLE. .A Chard MD. .I 200505 .U 90002057 .S Br J Rheumatol 9001; 28(5):374-8 .M Arthritis, Rheumatoid/CO/*GE/IM; Human; HLA-DQ Antigens/*GE; Restriction Fragment Length Polymorphisms/*; Rheumatoid Factor/AN. .T HLA-DO-related restriction fragment length polymorphisms in rheumatoid arthritis: evidence for a link with disease expression. .P JOURNAL ARTICLE. .W Eighty-three patients with rheumatoid arthritis (RA) were investigated for HLA-DQ and DR locus restriction fragment length polymorphisms (RFLP). Of the 83 patients, 61 (73%) possessed the DR4 allele and within this group we have investigated the relative frequencies of two DQ beta gene variants of DQw3, DQw7 and DQw8, one of which we had previously found to be raised in Felty's syndrome. This analysis revealed a significantly higher frequency of DQw7 containing haplotypes in DR4 positive rheumatoid patients (64%) than in DR-matched healthy controls (42%). Furthermore, the distribution of DQw7 was biased towards those patients with greater disability indicated by the HAQ score, more systemic disease and higher titres of rheumatoid factor, suggesting that DQw7 may contribute to disease expression. .A Sansom DM; Amin SN; Bidwell JL; Klouda PT; Bradley BA; Evison G; Goulding NJ; Hall ND; Maddison PJ. .I 200506 .U 90002058 .S Br J Rheumatol 9001; 28(5):379-82 .M Adolescence; Adult; Aged; Arthritis, Rheumatoid/IM; Autoantibodies/*AN; Cardiolipins/*IM; Enzyme-Linked Immunosorbent Assay; Female; Human; IgG/AN; IgM/AN; Kidney Diseases/ET; Lupus Erythematosus, Systemic/CO/*IM; Male; Middle Age; Predictive Value of Tests; Support, Non-U.S. Gov't. .T The relationship of anticardiolipin antibodies to disease activity in systemic lupus erythematosus. .P JOURNAL ARTICLE. .W Sera from 124 blood donors, 60 rheumatoid arthritis (RA) and 57 SLE patients were measured for anticardiolipin antibodies by ELISA. Significantly raised IgG (aCLG) and IgM (aCLM) anticardiolipin antibody levels were found in RA and SLE (p less than 0.0005). However, in SLE both aCLG and aCLM levels were significantly higher than in RA (p less than 0.0025). We then conducted a transectional study to evaluate aCL levels and disease activity in SLE. There was a good positive predictive value (70%) between aCL and overall disease activity, but not for individual systems. A strong association between aCL and renal involvement irrespective of activity was also found (80%). Nine SLE patients fulfilled both the clinical and serological criteria for the antiphospholipid syndrome (APS) and a further 18 patients fulfilled the serological criteria for APS. Results indicate that aCL levels are of value in predicting overall disease activity in SLE and in monitoring those patients who fulfil or partially fulfil the criteria for APS. .A Cooper RC; Klemp P; Stipp CJ; Brink S. .I 200507 .U 90002059 .S Br J Rheumatol 9001; 28(5):382 .M Arthritis, Psoriatic/*RH; Human; Physical Therapy/*. .T What is the best treatment approach for a patient with the mutilating pattern of psoriatic peripheral arthritis? .P JOURNAL ARTICLE. .A Wright V. .I 200508 .U 90002060 .S Br J Rheumatol 9001; 28(5):383-5 .M Adolescence; Amylases/ME; Arthritis, Juvenile Rheumatoid/*ME; Calcium/ME; Child; Chronic Disease; DMF Index; Female; Human; IgA/ME; Male; Muramidase/ME; Parotid Gland/*SE; Periodontal Index; Phosphates/ME; Potassium/ME; Saliva/*ME; Sodium/ME. .T Sialochemistry in juvenile chronic arthritis. .P JOURNAL ARTICLE. .W Stimulated parotid gland secretions collected from 16 patients with juvenile chronic arthritis (JCA) were analysed and the results compared with those obtained from 83 healthy sex-, age-, and socioeconomic status-matched children. Parotid salivary flow rate was measured and the saliva samples were assayed for calcium, phosphorus, potassium, chloride, sodium, urea, lysozyme, amylase and immunoglobulin levels (IgA, Ig, IgM). Our results showed that parotid flow rate (PFR) values in JCA patients were not statistically different from those in healthy controls. However, the mean salivary concentrations of calcium, phosphorus, potassium, lysozyme and IgA were significantly lower in the patients. These data could provide an explanation for the increased incidence of caries and gingivitis observed in JCA. .A Siamopoulou A; Mavridis AK; Vasakos S; Benecos P; Tzioufas AG; Andonopoulos AP. .I 200509 .U 90002062 .S Br J Rheumatol 9001; 28(5):393-8 .M Adrenal Cortex Hormones/TU; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid/BL/DT/*ME/RA; Female; Human; Male; Middle Age; Osteoarthritis/BL/*ME/RA; Osteocalcin/BL/*ME; Synovial Fluid/*ME. .T Serum and synovial fluid osteocalcin (bone gla protein) levels in joint disease [see comments] .P JOURNAL ARTICLE. .W Osteocalcin (bone gla protein) is a sensitive marker of bone turnover in metabolic disease. Using a well characterized antiserum (R 102M) we have assayed serum and synovial fluid samples from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) and related levels to serological and radiological markers of disease. There were 21 patients with RA (mean age 58.2 years, 15 F) and 33 with OA (mean age 69.2, 28 F). Paired serum and synovial fluids (SF) were available in 19 RA patients and 30 OA patients. Serum osteocalcin levels were related to age-/sex-matched normals and to a small group of elderly disease controls. Serum levels tended to be lower in RA than controls, but not significantly so: RA 5.56 (3.67); control 6.09 (2.54) ng/ml; expressed as mean (SD) and the mean serum/SF ratio was 0.88 (0.86). The results were much more variable in OA (mean serum osteocalcin 6.1 (3.9]. Elevated levels were mainly due to a small number of patients with a destructive form of OA and were higher than those with non-destructive OA (10.3 (3.5), n = 20, versus 3.83 (1.6), n = 10). Patients with non-destructive OA had a lower serum osteocalcin than age-/sex-matched normals. In this study, synovial fluid levels were usually less than serum concentrations, but in two RA and four OA patients the ratio was reversed, suggesting local production. Osteocalcin may be an important marker of bone activity in OA. .A Campion GV; Delmas PD; Dieppe PA. .I 200510 .U 90002063 .S Br J Rheumatol 9001; 28(5):399-403 .M Adult; Aged; Body Temperature Regulation/*PH; Chronic Disease; Cold/DU; Female; Hand/PH; Human; Male; Middle Age; Pain/PP; Reflex Sympathetic Dystrophy/*PP; Thermography. .T Reflex sympathetic dystrophy (algoneurodystrophy): temperature studies in the upper limb. .P JOURNAL ARTICLE. .W The temperature response of the hands to mild cold stress (20 degrees C for one minute) has been measured in 20 normal subjects, 20 patients with reflex sympathetic dystrophy (RSD) and 10 patients with chronic upper limb pain (CULP) of uncertain origin. The results of RSD and CULP groups were significantly (p less than 0.05) different from normal but were indistinguishable. For each patient, 11 variables obtained from the thermal stress test were compared with the normal range. Ten of the RSD group and seven of the CULP group had four or more abnormal variables and were considered to have a thermoregulatory abnormality. The thermal stress test is useful in the objective assessment of RSD. It is non-invasive, patient acceptable and reproducible. .A Cooke ED; Glick EN; Bowcock SA; Smith RE; Ward C; Almond NE; Beacham JA. .I 200511 .U 90002064 .S Br J Rheumatol 9001; 28(5):404-9 .M Adult; Aged; Colles' Fracture/*CO; Female; Hand; Human; Middle Age; Pain Measurement/*IS; Predictive Value of Tests; Radius Fractures; Reflex Sympathetic Dystrophy/ET/*PP; Support, Non-U.S. Gov't. .T The use of dolorimetry in the assessment of post-traumatic algodystrophy of the hand. .P JOURNAL ARTICLE. .W We have investigated the use of dolorimetry in the assessment of algodystrophy of the hand. Findings in 12 affected patients following Colles' fracture were compared with age- and sex-matched normal controls. Algodystrophy was associated with a significant increase in tenderness of both the finger joints and bones. Tenderness of the whole hand was quantified by summing the dolorimetry readings at each site within the hand and the ratio of the summed readings for the two hands was defined as the dolorimetry ratio. This ratio was highly reproducible and independent of external variables. It was significantly lower in patients with algodystrophy than in controls and may provide a method for the diagnosis and serial assessment of the disorder. .A Atkins RM; Kanis JA. .I 200512 .U 90002065 .S Br J Rheumatol 9001; 28(5):409 .M Acquired Immunodeficiency Syndrome/*CO/DI/PC; AIDS Serodiagnosis; Female; Human; Informed Consent; Male; Reiter's Disease/*ET; Risk Factors. .T Should all patients with Reiter's syndrome be tested for HIV infection? .P JOURNAL ARTICLE. .A Keat AC. .I 200513 .U 90002066 .S Br J Rheumatol 9001; 28(5):410-3 .M alpha 1-Antitrypsin/*ME; Adult; Double-Blind Method; Female; Human; IgA/*ME; Male; Middle Age; Salicylazosulfapyridine/*TU; Spondylitis, Ankylosing/*DT/IM. .T Sulphasalazine therapy in ankylosing spondylitis: its effect on disease activity, immunoglobulin A and the complex immunoglobulin A-alpha-1-antitrypsin. .P JOURNAL ARTICLE. .W Serum levels of immunoglobulin A (IgA) and the complex immunoglobulin A-alpha 1 antitrypsin (IgA-alpha 1AT) were measured at the commencement and after 3 months of a double-blind, placebo-controlled trial of sulphasalazine (SAS) in patients with active ankylosing spondylitis (AS). Twenty-eight patients were evaluated, 15 on sulphasalazine, 13 on placebo. Significant falls were seen in both IgA (p less than 0.01) and IgA-alpha 1AT (p less than 0.001) in the actively treated patients. In addition, significant improvement in clinical and laboratory measures of disease were observed. It is concluded that SAS is effective in AS and modulates the immune response. .A Davis MJ; Dawes PT; Beswick E; Lewin IV; Stanworth DR. .I 200514 .U 90002067 .S Br J Rheumatol 9001; 28(5):414-7 .M Adult; Aged; Aged, 80 and over; Anemia, Macrocytic/CI; Arthritis/*DT; Female; Hematologic Diseases/*CI; Human; Male; Middle Age; Retrospective Studies; Salicylazosulfapyridine/*AE. .T Haematological side-effects of sulphasalazine in inflammatory arthritis. .P JOURNAL ARTICLE. .W The nature and incidence of haematological side-effects of sulphasalazine was sought in a retrospective study of 130 sulphasalazine-treated patients with chronic inflammatory arthritis. Macrocytosis was seen to occur in 27 patients (20.8%) and four patients (3%) developed a macrocytic anaemia. Only eight of 23 macrocytic patients had low red cell folate levels, three of whom were anaemic. An increased risk of developing macrocytosis was seen with doses of sulphasalazine greater than 2 g per day. In most patients the macrocytosis was noted during the first 6 months but did occur in the second and third 6-month period of treatment. Only one patient (0.8%) developed neutropenia and no cases of thrombocytopenia were observed. Regular blood counts should be performed while patients remain on treatment but haematological side-effects are seldom the reason for withdrawal of sulphasalazine. .A Hopkinson ND; Saiz Garcia F; Gumpel JM. .I 200515 .U 90002068 .S Br J Rheumatol 9001; 28(5):418-21 .M Glycosides/*PD; Human; Mitotic Index/DE; Plant Extracts/*PD; Support, Non-U.S. Gov't; T-Lymphocytes/*DE. .T The effect of CPH 82 on the growth of human lymphocytes in vitro. Definition of cytobiological action. .P JOURNAL ARTICLE. .W A drug composed of two semisynthetic podophylline derivatives, CPH 82, has recently been launched for the treatment of severe rheumatoid arthritis. The present in vitro study of PHA-stimulated human T-lymphocytes showed that CPH 82 arrested cell division in a metaphase-like configuration. The cell cycle effects of CPH 82 were indistinguishable from the cell cycle effects of the classical microtubule depolymerizers, Colcemid (a colchicine derivative) and podophyllotoxin. A CPH 82 concentration of 1 microgram/ml, which is close to therapeutic serum concentrations, had an almost maximal effect on cell division. It is suggested that at least part of the anti-inflammatory effect of CPH 82 is due to a colchicine-like activity on, for example, proliferating lymphocytes. .A Rantapaa Dahlqvist S; Norberg B; Sondell K; Nordenson I; Holmgren G. .I 200516 .U 90002069 .S Br J Rheumatol 9001; 28(5):421 .M Arthritis, Rheumatoid/*CO; Diagnosis, Differential; Human; Leg Ulcer/*PA/TH; Varicose Ulcer/*PA. .T Rheumatoid leg ulcers are notoriously difficult to manage. How can one distinguish them from gravitational and large vessel ischaemic ulceration? What is the most effective treatment? .P JOURNAL ARTICLE. .A Lambert E; McGuire J. .I 200517 .U 90002070 .S Br J Rheumatol 9001; 28(5):422-3 .M Arthritis, Rheumatoid/*DT; Human; Injections, Intravenous; Methotrexate/*PK/TU; Synovial Fluid/*ME. .T Synovial and serum levels of methotrexate during methotrexate therapy of rheumatoid arthritis. .P JOURNAL ARTICLE. .W Methotrexate (MTX) levels were studied following intravenous MTX in both serum and synovial fluid (SF) of rheumatoid arthritis patients. Two hours after injection serum MTX levels were higher than those of SF. At 24 hours SF levels of MTX exceeded those of the serum, while at 72 hours both blood and SF concentrations were undetectable. The localization of parenteral MTX in the SF may have importance in the understanding of its mechanism and site of action in rheumatoid arthritis. .A Tishler M; Caspi D; Graff E; Segal R; Peretz H; Yaron M. .I 200518 .U 90002071 .S Br J Rheumatol 9001; 28(5):424-7 .M Adult; Arthritis, Rheumatoid/BL/*DT; Blood Sedimentation/DE; Double-Blind Method; Erythrocyte Deformability/*DE; Female; Human; Male; Middle Age; Random Allocation; Ticlopidine/*TU. .T Correlation between clinical and laboratory findings when the whole blood filterability rate is modified by ticlopidine in the treatment of rheumatoid arthritis. .P JOURNAL ARTICLE. .W This double-blind study assessed the effects of oral ticlopidine versus placebo on whole blood filterability in two homogenous groups of 20 rheumatoid arthritis patients taking one NSAID. The patients' clinical progress was monitored to see if modifications in the whole blood filterability rate could be correlated with any improvement in the clinical picture. Our results showed treatment with ticlopidine significantly (p less than 0.01) improved both the ESR (-28%) and the whole blood filterability rate (-15%), pain (-24%), and morning stiffness (-28%). These clinical benefits correlated with improvement in the whole blood filterability rate. Clinical benefits may have resulted from improved perfusion and transport of NSAID to target tissues. .A Ciuffetti G; Ciacca A; Mercuri M; Lombardini R; Maragoni G; Scarponi AM. .I 200519 .U 90002072 .S Br J Rheumatol 9001; 28(5):436-9 .M Arthritis, Rheumatoid/*MI; Human; Research. .T Microbiology will give the real answers to rheumatoid arthritis. .P JOURNAL ARTICLE. .A Ford DK. .I 200520 .U 90002073 .S Br J Rheumatol 9001; 28(5):440-2 .M Adult; Case Report; Diagnosis, Differential; Human; Lupus Erythematosus, Systemic/*DI; Male; Polyradiculoneuritis/*DI. .T A case of systemic lupus erythematosus presenting as Guillain-Barre syndrome. .P JOURNAL ARTICLE. .W Acute demyelinating polyneuropathy has been reported only twice as a presenting feature of systemic lupus erythematosus (SLE) in female patients. We report a male presenting with an acute demyelinating polyneuropathy who subsequently was found to have SLE. .A Chaudhuri KR; Taylor IK; Niven RM; Abbott RJ. .I 200521 .U 90002074 .S Br J Rheumatol 9001; 28(5):443-5 .M Adult; Calcinosis/*ET/RA; Case Report; Human; Hypercalcemia/ET; Male; Muscular Diseases/*ET/RA; Myositis Ossificans/*CO; Remission, Spontaneous; Support, Non-U.S. Gov't; Tomography, X-Ray Computed. .T Myositis ossificans non-progressiva--reversible muscle calcification in polymyositis [see comments] .P JOURNAL ARTICLE. .W We report a case of muscle calcification, a rare complication of polymyositis, documented on muscle biopsy and computerized tomography scanning. As the calcification resolved radiologically, marked hypercalcaemia developed requiring forced diuresis. .A Coakley JH; Smith PE; Jackson MJ; Edwards RH; Carty AT. .I 200522 .U 90002076 .S Br J Rheumatol 9001; 28(5):451 .M Bursitis/*ET; Case Report; Female; Human; Middle Age; Shoulder Joint; Thyroiditis, Autoimmune/*CO. .T Bilateral adhesive capsulitis and Hashimoto's thyroiditis [letter] .P LETTER. .A Summers GD; Gorman WP. .I 200523 .U 90002077 .S Br J Rheumatol 9001; 28(5):451-3 .M Exertion; Human; Nomenclature; Occupational Diseases/*PP; Pain/*ET; Repetition Strain Injury/*PP. .T Regional pain syndrome [letter; comment] .P COMMENT; LETTER. .I 200524 .U 90002078 .S Br J Rheumatol 9001; 28(5):453-4 .M Ambulatory Care Facilities/*OG; Appointments and Schedules/*; Great Britain; Rheumatology/*OG. .T Consultant appointments and their effect on outpatient appointments [letter] .P LETTER. .A Kirwan JR; Dieppe P; Snow S. .I 200525 .U 90002079 .S Br J Rheumatol 9001; 28(5):454-6 .M Attitude to Health/*; Human; Patient Education/*MT; Physician-Patient Relations; Rheumatic Diseases/PX/TH. .T The patient is not a blank sheet [letter; comment] .P COMMENT; LETTER. .A Langer HE; Bormann H; Birth U. .I 200526 .U 90002080 .S Br J Rheumatol 9001; 28(5):456 .M Arthritis, Rheumatoid/*DT; Azathioprine/*TU; Case Report; Drug Therapy, Combination; Female; Human; Middle Age; Salicylazosulfapyridine/*TU. .T The use of sulphasalazine and azathioprine in combination to treat rheumatoid arthritis [letter] .P LETTER. .A Waterworth RF. .I 200527 .U 90002081 .S Br J Rheumatol 9001; 28(5):456-7 .M Adnexitis/*CO; Backache/*ET; Female; Human; Sacroiliac Joint/RI; Technetium Tc 99m Pertechnetate/DU. .T Back pain in women with chronic pelvic inflammatory disease and inflammatory sacroiliac disease [letter] .P LETTER. .A Celinska E; Spring J; Denham A; Seldrup J; Chapman M; Welsh KI; Panayi GS. .I 200528 .U 90002082 .S Br J Rheumatol 9001; 28(5):457-8 .M Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid/*CO; Female; Human; Male; Middle Age; Motor Neurons/*; Neuromuscular Diseases/*CO. .T An association between RA and motor neurone disease? [letter; comment] .P COMMENT; LETTER. .A Outhwaite JM; Smith J; Cochrane GM. .I 200529 .U 90002084 .S Br J Rheumatol 9001; 28(5):458-9 .M Antibodies, Monoclonal/*DU; Cross Reactions; Human; Rheumatoid Factor/AN; Sjogren's Syndrome/BL/*DI. .T Monoclonal anti-cross-reactive idiotype antibodies as possible probes for lymphoproliferation in primary Sjogren's syndrome [letter] .P LETTER. .A Shokri F; Mageed RA; Jefferis R; Kitas GD; Katsikis P; Moutsopoulos HM. .I 200530 .U 90002088 .S Br J Radiol 9001; 62(741):785-9 .M Ear Neoplasms/RA/*RT; Ear, Middle/*; Human; Parotid Neoplasms/RA/*RT; Radiotherapy Planning, Computer-Assisted/*; Radiotherapy, Computer-Assisted/*; Support, Non-U.S. Gov't; Tomography, X-Ray Computed/*. .T Treatment of tumours of the parotid gland and middle ear using obliquely reconstructed computed tomographic images. .P JOURNAL ARTICLE. .W Conventional planning of radiotherapy of tumours of the parotid, middle ear and other tumours in the head and neck often requires the treatment plane to be non-transverse. This produces major problems in delineating the tumour as well as verifying that vital structures such as the spinal cord are not included in the target volume. The use of computed tomography (CT) generally overcomes some of these problems and we have developed an algorithm to reconstruct transverse CT images into the appropriate oblique plane. Software has been written on the Picker Independent Treatment Planning System (ITPS) to allow planning on central axis and off-axis oblique planes. In addition we have used a beam's eye view facility to aid in the verification process. .A Sims C; Manifold IH; Conway J. .I 200531 .U 90002089 .S Br J Radiol 9001; 62(741):790-5 .M Adult; Aged; Bone and Bones/*IN; Bone Marrow/*RI; Female; Femoral Neck Fractures/CO; Femur Head Necrosis/ET/RI; Human; Male; Middle Age; Osteonecrosis/ET/*RI; Pilot Projects; Technetium Tc 99m Aggregated Albumin/*DU; Technetium Tc 99m Medronate. .T Bone marrow scintigraphy in the diagnosis of post-traumatic avascular necrosis of bone. .P JOURNAL ARTICLE. .W A series of 19 patients, who were clinically suspected of developing avascular necrosis of bone following fracture, were entered into a pilot study comparing the use of bone marrow scintigraphy with conventional skeletal scintigraphy. Two-phase bone scintigraphy, using 600 MBq of 99Tcm-HMDP, and perfusion and late-phase nanocolloid scintigraphy, using 370 MBq of 99Tcm-nanocolloid, were performed on each patient. In both methods, photon deficiency at the site of interest was taken to indicate avascularity. The perfusion phase of both methods was found to be unhelpful. Agreement between methods was obtained in 18 patients (95%). Six patients had abnormal nanocolloid scans, one of which was normal on the conventional bone scintigram. The remaining 13 patients had no evidence to suggest avascularity in either method. Three of the patients with abnormal scans have had hip replacement surgery following which avascularity of the femoral head was confirmed. 99Tcm-nanocolloid scintigraphy is thus shown to be a very sensitive method of demonstrating avascularity of bone following trauma. .A Tawn DJ; Watt I. .I 200532 .U 90002092 .S Br J Radiol 9001; 62(741):807-12 .M Adult; Aged; Barium Sulfate/*DU; Enema/*; Female; Human; Male; Middle Age; Radiation Injuries/*RA; Radiotherapy/AE; Rectal Diseases/ET/*RA; Sigmoid Diseases/ET/*RA; Time Factors. .T Late radiation injury of the rectum and sigmoid colon: barium enema findings in 92 patients. .P JOURNAL ARTICLE. .W We reviewed the findings on 169 contrast enema examinations in 92 patients with late radiation injury of the rectum and sigmoid colon, encountered over an 11-year period. The diagnosis was made by rectosigmoidoscopy in all patients. The limitations and pitfalls of both examinations were studied. The mean interval between radiotherapy and diagnosis was 1.7 years and the mean follow-up period was 3.5 years. The main radiological features varied from normal findings (15% of the initial examinations) to decreased distensibility of the bowel wall, intestinal fixation, mucosal and contour abnormalities, ulceration, stenoses and fistula formation. During follow-up, the number of all pathological findings increased. Pre-stenotic dilatation of the descending colon was always absent. The contrast enema examinations and endoscopies were found to be complementary. The barium enema showed the extent of the disease and accurately identified stenoses and fistulas, but underdiagnosed ulceration and overdiagnosed malignancy. Endoscopy allowed unequivocal detection of mucosal damage, especially ulceration, and was accurate in showing stenoses but sometimes failed to demonstrate fistulas. Moreover, in 25% of examinations it was impossible to examine the entire abnormal area. .A den Hartog Jager FC; Cohen P; van Haastert M. .I 200533 .U 90002093 .S Br J Radiol 9001; 62(741):813-6 .M Angiography, Digital Subtraction/*AE; Cerebral Angiography/*AE; Cerebrovascular Disorders/*RA; Contrast Media/AD/*AE; Human; Injections, Intravenous. .T Relative safety of intravenous digital subtraction angiography over other methods of carotid angiography and impact on clinical management of cerebrovascular disease. .P JOURNAL ARTICLE. .W Data from a multicentre survey based on three London teaching hospitals on the relative safety and clinical utility of intravenous carotid digital subtraction angiography (DSA) over intra-arterial DSA and conventional carotid angiography are presented. The incidence of stroke during intra-arterial DSA was 0.7% (n = 538) and during conventional angiography was 0.8% (n = 780). The incidence of stroke during intravenous DSA was zero (n = 3710). When it constituted the initial investigation, intravenous DSA achieved a 93.8% replacement value over intra-arterial studies as a whole (n = 474) and 89% replacement value for patients having carotid endarterectomy (n = 99). It was also noted that the installation of DSA equipment at one unit coincided with a sixfold increase in the number of carotid angiographic examinations and an almost threefold increase in carotid endarterectomies. .A Stevens JM; Barter S; Kerslake R; Schneidau A; Barber C; Thomas DJ. .I 200534 .U 90002094 .S Br J Radiol 9001; 62(741):817-23 .M Computer Graphics; Computer Simulation/*; Human; Radiography/*; ROC Curve/*. .T Assessment of feature size abnormalities using receiver operating characteristic analysis. .P JOURNAL ARTICLE. .W The ability of an observer to detect variations in size of a geometrical image feature have been investigated using receiver operating characteristic (ROC) analysis. Three types of image were constructed using computer graphics: disc-shaped targets of variable radius, model chest radiographs showing a variable heart diameter and model arterial angiograms with variable vessel width. Five factors were investigated: observer experience, variation of detectability with theoretical signal-to-noise ratio, the prior probability of the presence of an abnormality, viewing distance, and uncertainty in the location of an abnormality. In all but one experiment, excellent agreement was found between measured detectabilities and the predictions of signal detection theory, providing an initial practice session was included for each observer. No significant variation in detectability was found using six different prior probabilities and two different viewing distances, and the reduction in detectability for a four-alternative location task was in good agreement with theoretical predictions. The high statistical efficiencies found for the detection of geometrical signals suggest that the levels of observer "internal" noise arising from decision-making processes during an ROC experiment are very low. .A Warren RC; Darwin CJ. .I 200535 .U 90002096 .S Br J Radiol 9001; 62(741):830-7 .M Animal; Biomechanics; Dose-Response Relationship, Radiation; Female; Skin/PA/PP/*RE; Support, Non-U.S. Gov't; Swine. .T The effects of single doses of X rays on the mechanical properties of pig skin in vivo. .P JOURNAL ARTICLE. .W Changes in the mechanical properties of pig skin have been studied in vivo, using a dermal extensometer, after irradiation with a single dose of 18 Gy of X rays. There was no significant change in the stiffness of irradiated skin, when compared with unirradiated skin, until 9 weeks after irradiation when the irradiated skin was significantly stiffer. This effect was also found at 12 and 15 weeks after irradiation. When the increase in skin thickness, as a consequence of oedema, was taken into account a significant increase in the unrelaxed elastic modulus of irradiated skin was only seen at 12 and 15 weeks after irradiation. There were no significant changes in force relaxation, after extension of the skin, over this time period. After the resolution of oedema, which was associated with a significant 20% reduction in the thickness of irradiated skin relative to unirradiated skin, the mechanical properties of irradiated skin were not markedly different from those of unirradiated skin. However, between 30 and 39 weeks after irradiation there was a further wave of dermal thinning, resulting in a total reduction in the thickness of irradiated skin relative to unirradiated skin of 26%. This was associated with a rapid rise in the skin stiffness and unrelaxed elastic modulus by approximately 65 and approximately 140%, respectively. It was only at these late times after irradiation that the force relaxation of the skin was modified significantly. At 9 and 12 weeks after irradiation the reduction in skin stiffness and the unrelaxed elastic modulus were dose related. Based on the percentage of fields showing a significant reduction in these biomechanical parameters, ED50 values of between 12 and 14.5 Gy were established. This would appear to be a sensitive method for assessing radiation-induced dermal changes since few gross changes are observed in this dose range. .A Baker MR; Bader D; Hopewell JW. .I 200536 .U 90002097 .S Br J Radiol 9001; 62(741):838-42 .M Angiocardiography/*; Angiography, Digital Subtraction/*; Carotid Arteries/*RA; Human; Models, Structural; Radiation Dosage. .T Organ doses from cardiac and carotid digital subtraction angiography. .P JOURNAL ARTICLE. .W Estimates of mean organ doses from cardiac and carotid digital subtraction angiography (DSA) are obtained from measurements done using a Rando-Alderson tissue-equivalent phantom. Thermoluminescent dosemeter chips and discs were calibrated and used for all measurements in the primary and scattered radiation fields. Skin doses as well as mean doses received by the thyroid, lung, lens of the eye, breast, uterus and the ovaries were measured. A 30 degree right anterior oblique (RAO) cardiac DSA study produces a beam entrance dose of about 121 mGy at a rate of 0.48 mGy/frame. The highest mean organ dose from cardiac DSA was to the lung with a value of 14.4 mGy. The rest of the organs received doses below 1 mGy. In carotid DSA, the mean entrance doses resulted from the RAO, left anterior oblique, and the Towne's view projections give an average of 168 mGy at a rate of 8.4 mGy/frame. The highest mean organ dose from the three projections, 21 mGy, was received by the thyroid. The uterus and ovaries received the lowest doses from both procedures with values below 0.04 mGy. Patient and phantom surface exposures were compared using an exposure area product system. Hence, exposure conditions used for measuring organ doses on the phantom were adjusted to resemble those used for patients. .A Mustafa AA; Janeczek J. .I 200537 .U 90002098 .S Br J Radiol 9001; 62(741):843-8 .M Animal; Bronchopneumonia/ET; Cholelithiasis/*TH; Hemorrhage/*ET; Lithotripsy/*AE; Lung Diseases/*ET; Models, Biological; Swine. .T Soft-tissue effects of biliary extracorporeal shockwave lithotripsy in swine. .P JOURNAL ARTICLE. .W This study investigates the soft-tissue effects of biliary extracorporeal shockwave lithotripsy (BESWL) using a recently developed lithotripter, which consists of an electromagnetic shockwave generator and an integrated ultrasonic targeting system. Sixteen swine, evenly divided into four groups, underwent BESWL. One group had one BESWL session targeted on the gallbladder and another group had two BESWL sessions targeted on the gallbladder. The third group had one BESWL session targeted on implanted gallbladder stones and the fourth group had one BESWL session targeted on the region of the common bile duct (CBD). Half of each group were sacrificed on the day of lithotripsy and half 1 week later. Post-mortem examinations were performed. Each implanted gallstone had fragmented. There were no findings attributable to BESWL in 11 animals. Three animals had pulmonary haemorrhagic spots (the largest was 10 mm in diameter) and one had a submucosal CBD petechia; these findings were attributable to BESWL. In two animals, microscopic haemorrhage associated with bronchopneumonia (usually present in our pig population) was more prominent than usual. This was possibly attributable to BESWL. The swine's deep posterior costophrenic sulcus makes it difficult to avoid the lung base during BESWL in swine. We conclude that this BESWL device can fragment gallstones without causing clinically significant soft-tissue damage. .A Malone DE; Becker CD; Reich D; Quenville NF; Burhenne HJ. .I 200538 .U 90002099 .S Br J Radiol 9001; 62(741):849-53 .M Antineoplastic Agents, Combined/TU; Carcinoma, Squamous Cell/DT/*RT; Combined Modality Therapy; Female; Human; Lymphatic Irradiation; Male; Middle Age; Remission Induction; Retrospective Studies; Tongue Neoplasms/DT/*RT. .T Squamous cell carcinoma of the base of the tongue: results of treatment in 115 cases. .P JOURNAL ARTICLE. .W Between 1976 and 1986, we treated 115 patients (mean age 53.8 years) with base of tongue carcinomas. The staging system used was the UICC TNM classification of 1979. Seventy per cent of the tumours were T3 or T4 and 42% had N2 or N3 lymph node. Locoregional treatment was irradiation alone (98/115) or surgery and post-operative radiotherapy (17/115). Sixty-seven patients received induction chemotherapy. Actuarial survival of the entire group at 3 and 5 years was 25 and 23%, respectively, and 3-year actuarial survival rates for T1, T2, T3 and T4 lesions were 42, 48, 20 and 17%, respectively. The local control rate at the primary site was 55% and 78% in the neck. Distant metastases occurred in 10% of patients and 8% had a second primary. Nodal status was the only other prognostic factor. The local control rate obtained with irradiation alone was not good. For limited T1 and T2 tumours, interstitial therapy or surgery should improve the local control rate. .A Calais G; Reynaud-Bougnoux A; Bougnoux P; Le Floch O. .I 200539 .U 90002100 .S Br J Radiol 9001; 62(741):854-6 .M Adolescence; Buttocks; Child; Child, Preschool; Female; Fibroma/*RT; Human; Male; Muscular Diseases/*RT; Shoulder; Thigh. .T Radiotherapy in the management of aggressive fibromatosis. .P JOURNAL ARTICLE. .A Atahan IL; Akyol F; Zorlu F; Gurkaynak M. .I 200540 .U 90002101 .S Br J Radiol 9001; 62(741):856-9 .M Adult; Antineoplastic Agents, Combined/*TU; Bleomycins/AD; Carcinoma, Squamous Cell/*DT/SC; Case Report; Cervix Neoplasms/*DT; Cisplatin/AD; Female; Human; Lung Neoplasms/SC; Methotrexate/AD; Neoplasm Staging; Remission Induction. .T Sustained complete remission of stage IVb carcinoma of the cervix with cis-platinum, methotrexate and bleomycin chemotherapy [see comments] .P JOURNAL ARTICLE. .A Burnet NG; Blake PR. .I 200541 .U 90002102 .S Br J Radiol 9001; 62(741):859-61 .M Amyloidosis/*DI; Bone Diseases/*DI; Case Report; Diagnosis, Differential; Human; Male; Middle Age. .T Atypical amyloidosis of bone. .P JOURNAL ARTICLE. .A Daly BD; Moore DP. .I 200542 .U 90002103 .S Br J Radiol 9001; 62(741):862-4 .M Case Report; Child, Preschool; Female; Human; Osteochondrodysplasias/*RA. .T Spondylo-metaphyseal dysplasia of Sutcliffe type. .P JOURNAL ARTICLE. .A Kozlowski K; Bellemore MC. .I 200543 .U 90002104 .S Br J Radiol 9001; 62(741):864-6 .M Aged; Carcinoma, Transitional Cell/DI/*UR; Case Report; Female; Hematuria/*ET; Human; Ureteral Neoplasms/DI/*UR; Urine/CY. .T Asymptomatic haematuria and abnormal urine cytology. .P JOURNAL ARTICLE. .A Rao A; Kagan AR; Steckel RJ. .I 200544 .U 90002105 .S Br J Radiol 9001; 62(741):867-8 .M Adult; Arachnoid/*; Case Report; Cysts/CO/*RA; Female; Hematoma, Subdural/CO/*RA; Human. .T A real headache! [see comments] .P JOURNAL ARTICLE. .A Jackson JE; O'Donnell CJ. .I 200545 .U 90002106 .S Br J Radiol 9001; 62(741):869-70 .M Animal; Hematoporphyrin Photoradiation/*; Magnetic Resonance Imaging/*; Male; Mammary Neoplasms, Experimental/DI/*DT; Mice; Photochemotherapy/*; Predictive Value of Tests/*; Support, Non-U.S. Gov't. .T Proton nuclear magnetic resonance imaging as a predictor of the outcome of photodynamic therapy of tumours. .P JOURNAL ARTICLE. .A Moore JV; Dodd NJ; Wood B. .I 200546 .U 90002108 .S Br J Radiol 9001; 62(741):873-4 .M Cell Division/RE; Human; Models, Biological/*; Radiotherapy Dosage/*. .T Biological equivalence between fractionated radiotherapy treatments using the linear-quadratic model [letter; comment] .P COMMENT; LETTER. .A Yaes RJ; Feola J; Wierzbicki J; Urano M; Maruyama Y. .I 200547 .U 90002110 .S Br J Radiol 9001; 62(741):876 .M Adult; Case Report; Esophageal Stenosis/*RA; Female; Human. .T Transient circular narrowing of the cervical oesophagus [letter; comment] .P COMMENT; LETTER. .A Dantas RO. .I 200548 .U 90002626 .S Can Med Assoc J 9001; 141(7):647 .M Human; War Crimes/*/PX. .T "Lest we forget" [editorial] .P EDITORIAL. .A Squires BP. .I 200549 .U 90002627 .S Can Med Assoc J 9001; 141(7):651-2 .M Acquired Immunodeficiency Syndrome/*DI; Female; Human; HIV Seropositivity; Male; Ontario. .T Anonymous AIDS testing [letter] .P LETTER. .A Mackie ID. .I 200550 .U 90002628 .S Can Med Assoc J 9001; 141(7):652 .M Contrast Media/*; Human; Ions; Research Design. .T Nonionic contrast media [letter] .P LETTER. .A Doris CI. .I 200551 .U 90002629 .S Can Med Assoc J 9001; 141(7):653, 656 .M Human; Jurisprudence/*; Mental Disorders/*/DI/TH; Nursing Homes/*; Patient Advocacy/*. .T Who should determine competence? [letter; comment] .P COMMENT; LETTER. .A Watt G. .I 200552 .U 90002630 .S Can Med Assoc J 9001; 141(7):656-7 .M Human; Marfan Syndrome/*/DI. .T Marfan's syndrome [letter] .P LETTER. .A Gilchrist DM; Hayden MR. .I 200553 .U 90002631 .S Can Med Assoc J 9001; 141(7):657 .M Accident Prevention/*; Electric Injuries/PC; Electricity/*; Hospitals/*; Human; Safety/*. .T Electrical safety in patient care areas [letter] .P LETTER. .A Rasaiah B. .I 200554 .U 90002632 .S Can Med Assoc J 9001; 141(7):657 .M Attitude of Health Personnel; Education, Medical/*; Human; Physicians. .T Ranking the MD degree [letter] .P LETTER. .A Warner HA. .I 200555 .U 90002633 .S Can Med Assoc J 9001; 141(7):657-60 .M Human; Lung Neoplasms/*MO; Occupational Diseases/*MO; Smoking/*/MO. .T Good sense in medical science [letter; comment] .P COMMENT; LETTER. .A Morgan WK. .I 200556 .U 90002634 .S Can Med Assoc J 9001; 141(7):660-1 .M Costs and Cost Analysis; Ethics, Medical/*; Human; Organ Procurement/*/EC. .T Economics versus ethical acceptability [letter; comment] .P COMMENT; LETTER. .A Primeau F. .I 200557 .U 90002635 .S Can Med Assoc J 9001; 141(7):661-2 .M Abbreviations/*. .T Abbreviations and acronyms [letter] .P LETTER. .A Cheng TO. .I 200558 .U 90002638 .S Can Med Assoc J 9001; 141(7):663 .M Child; Ethics, Medical/*; Human; Human Experimentation; Philosophy, Medical/*. .T Philosophers at the bedside [letter] .P LETTER. .A Chance GW. .I 200559 .U 90002639 .S Can Med Assoc J 9001; 141(7):666-7 .M Human; Peer Review; Publishing/*; Writing/*. .T Editorials and platform articles: what editors want from authors and peer reviewers [editorial] .P EDITORIAL. .A Squires BP. .I 200560 .U 90002641 .S Can Med Assoc J 9001; 141(7):673-6 .M Canada; Education, Medical, Graduate/*; Human; Internship and Residency/*; Licensure, Medical; School Admission Criteria; Schools, Medical; Specialties, Medical/*ED. .T The specialty match: a necessity in the equitable resident selection process. .P JOURNAL ARTICLE. .W For many years directors of Canadian postgraduate specialty programs have selected candidates in an uncontrolled and haphazard way. Candidates and programs alike have therefore been unfairly treated. Since 1986 the Canadian Intern and Resident Matching Service has offered a centrally coordinated matching program to allow candidates to select specialty programs at centres of their choice and program directors to rate candidates. The result has been an effective method to achieve fairness in the selection of postgraduate trainees for participating Canadian specialty programs. .A Taylor B; Banner SR. .I 200561 .U 90002642 .S Can Med Assoc J 9001; 141(7):677-82 .M Adolescence; Adult; Aged; Canada; Cause of Death; Comorbidity; Comparative Study; Diabetes Mellitus/MO; Female; Human; Kidney Failure, Chronic/*MO/SU/TH; Kidney Transplantation/MO; Life Tables; Male; Middle Age; Probability; Registries; Risk Factors; Survival Rate. .T Mortality rates among patients with end-stage renal disease in Canada, 1981-86. .P JOURNAL ARTICLE. .W We assessed the mortality rates by age, sex, race, blood type, primary diagnosis, treatment and transplantation history of 8432 patients in Canada for whom end-stage renal disease (ESRD) was diagnosed between 1981 and 1986. Significant differences in the probability of dying were found between those with and without diabetes mellitus, between those who had received a renal transplant and those who had not, between white and nonwhite patients and between various age groups. The mortality rates of the ESRD patients were at least three times higher than those of the general Canadian population. Primary diagnosis and treatment were significantly associated with the risk of dying among the ESRD patients. For those who had received a transplant, the length of time spent waiting for a transplant was positively associated with the risk of death from ESRD. Patients who had received peritoneal dialysis before transplantation had a higher risk of death than those who had received either hemodialysis (risk ratio 1.3) or transplantation (risk ratio 3.2) as the first treatment. No significant differences were found in the cause of death between those who had received peritoneal dialysis and those who had received hemodialysis. Almost half of the deaths among women without diabetes who had received a transplant were due to infection. .A Silins J; Fortier L; Mao Y; Posen G; Ugnat AM; Brancker A; Gaudette L; Wigle D. .I 200562 .U 90002643 .S Can Med Assoc J 9001; 141(7):685-91 .M Adolescence; Adult; Air Pollutants/*AE; Alberta; Chemical Industry/*; Child; Cohort Studies; Cross-Sectional Studies; Environmental Exposure; Female; Fossil Fuels/*; Gases/*AE; Health; Human; Male; Mortality; Neoplasms/EP; Prevalence; Support, Non-U.S. Gov't. .T Chronic exposure to sour gas emissions: meeting a community concern with epidemiologic evidence. .P JOURNAL ARTICLE. .W For 25 years residents of a rural area in southwestern Alberta have complained of health problems attributed to sour gas emissions from nearby natural gas refineries. We undertook a large epidemiologic study of the current health status and the selected morbidity rates among 2152 people in the exposed area. We established two comparison groups: one was a demographically similar unexposed population and the other a demographically different group also exposed to sour gas emissions in another region. The methods included a cross-sectional survey of current residents and separate historical cohort studies involving registry linkage to investigate cancer incidence and all-cause mortality. The cross-sectional survey involved a comprehensive health questionnaire, standardized clinical examinations by physicians blinded to the subjects' symptoms and concerns, and several laboratory tests. We were able to contact just under 60% of the people who we knew had moved from each area since 1958 and found no evidence of selective migration for health reasons. Although the residents of the exposed area reported an excess number of symptoms and health problems there were no significant differences in the mortality rate, incidence of cancer, reproductive problems, major ailments, hair levels of arsenic and certain metals or respiratory function between the groups. .A Spitzer WO; Dales RE; Schechter MT; Suissa S; Tousignant P; Steinmetz N; Hutcheon ME. .I 200563 .U 90002644 .S Can Med Assoc J 9001; 141(7):693-7 .M Antineoplastic Agents, Combined/TU; Asparaginase/AD/TO/*TU; Boston; Child; Clinical Protocols; Female; Human; Infant; Leukemia, Lymphocytic, Acute/*DT/MO; Male; Methotrexate/AD; Neoplasm Recurrence, Local; Ontario; Prednisone/AD; Remission Induction; Risk Factors; Survival Rate; Vincristine/AD; 6-Mercaptopurine/AD. .T Management of Ontario children with acute lymphoblastic leukemia by the Dana-Farber Cancer Institute protocols. .P JOURNAL ARTICLE. .W There is ample evidence of the value of intensive therapeutic strategies in the management of acute lymphoblastic leukemia (ALL), the commonest form of malignant disease in children. Such a program, devised at the Dana-Farber Cancer Institute (DFCI), Boston, and incorporating high-dose L-asparaginase, was adopted in 1984 by the Children's Hospital at Chedoke-McMaster, Hamilton, Ont., and the Children's Hospital of Western Ontario, London. We describe the experience of these institutions in the treatment of 82 children with ALL, 19 of whom were switched to the DFCI protocols while in continuing first remission with other treatment programs to complete a minimum of 2 years of maintenance therapy; the remaining 63 children, who had recently diagnosed disease, were consecutively enrolled in the DFCI protocols. Each child was assigned at diagnosis to a category of risk for relapse and treated accordingly. There were no remission induction failures or deaths due to induction therapy among the patients with newly diagnosed disease. There were no differences in total or event-free survival rates between the patients in Hamilton and those in London or between those whose protocols were switched and those who were treated from the beginning with the DFCI protocols. With a median follow-up interval of 144 weeks the total survival rate was 95% and the event-free survival rate 88%. For patients at standard risk of relapse the event-free survival rate was 100%, for those at high risk the rate was 82%, and for those at very high risk the rate was 67%. If infants (all of whom suffered a relapse) are excluded from the last category the rate was 89%. These results were achieved with moderate toxic effects (except for two deaths, one of which was due to a therapeutic misadventure) and suggest that the prospect for cure in children with ALL. may now approximate 80%, a degree of success that demands that consideration be given to reducing total therapy, at least for children with standard-risk disease. Further follow-up will determine whether these high event-free survival rates will stabilize and meet the criteria for cure. .A Desai SJ; Barr RD; Andrew M; deVeber LL; Pai MK. .I 200564 .U 90002646 .S Can Med Assoc J 9001; 141(7):703 .M Acquired Immunodeficiency Syndrome/*PC; Canada; Developing Countries; Female; Human; Male. .T AIDS poses unique problems for CUSO, spokesman says [news] .P NEWS. .I 200565 .U 90002647 .S Can Med Assoc J 9001; 141(7):705-6 .M Abortion, Induced/*; Attitude of Health Personnel/*; Canada; Female; Human; Organizations; Physicians/*; Pregnancy; Societies, Medical. .T CPL poll on abortion angers many physicians [see comments] .P JOURNAL ARTICLE. .A Sullivan P. .I 200566 .U 90002649 .S Can Med Assoc J 9001; 141(7):708 .M Attitude of Health Personnel/*; Canada; Human; Nuclear Warfare/*; Physicians/*. .T It's time to cease fire. .P JOURNAL ARTICLE. .A Leith M. .I 200567 .U 90002651 .S Can Med Assoc J 9001; 141(7):712 .M Forensic Medicine/*; Human; Jurisprudence/*; Wit and Humor/*. .T "Were you kicked in the fracas?" .P JOURNAL ARTICLE. .A MacDonald PV. .I 200568 .U 90002652 .S Can Med Assoc J 9001; 141(7):713 .M Canada; Employment/*; Human; Personnel Management/*LJ; Practice Management, Medical/*. .T Be wary of wrongful-dismissal suits. .P JOURNAL ARTICLE. .A Carnerie F. .I 200569 .U 90002653 .S Can Med Assoc J 9001; 141(7):714-7 .M Aircraft/*; Environmental Monitoring; Environmental Pollution/AE; Eskimos/*; Health Status Indicators/*; Hearing Disorders/ET; Human; Newfoundland; Noise; Noise, Transportation/*AE. .T Low-level flying in Labrador: does it pose a health risk? .P JOURNAL ARTICLE. .A Goldman B. .I 200570 .U 90002654 .S Can Med Assoc J 9001; 141(7):720, 725, 727 .M Aged; Aging/*; Attitude of Health Personnel/*; Canada; Health Behavior/*; Human; Physicians/*; Societies, Medical. .T Doctors guilty of "ageism and indifference", MD tells General Council. .P JOURNAL ARTICLE. .A Sullivan P. .I 200571 .U 90002655 .S Can Med Assoc J 9001; 141(8):763-5 .M Holistic Health; Human; Writing/*. .T "Quackbusting" revisited [letter] .P LETTER. .I 200572 .U 90002656 .S Can Med Assoc J 9001; 141(8):765 .M Bicycling/*ST; Head Protective Devices/*; Human; Protective Devices/*. .T Bicycle helmet subsidy program [letter] .P LETTER. .A Morris BA. .I 200573 .U 90002657 .S Can Med Assoc J 9001; 141(8):765 .M Delivery/*; Female; Home Childbirth/*; Human; Pregnancy. .T So you want to have the baby at home? [letter; comment] [see comments] .P COMMENT; LETTER. .A Nisker JA; Benzie RJ. .I 200574 .U 90002658 .S Can Med Assoc J 9001; 141(8):765-7 .M Aged; Female; Human; Mammography/*; Middle Age; Patient Compliance; Physicians, Family. .T Mammography screening by family physicians [letter] .P LETTER. .A McAuley RG; Lusk S. .I 200575 .U 90002659 .S Can Med Assoc J 9001; 141(8):767 .M Child; Child Abuse, Sexual/*; Human. .T Examination of sexually abused children [letter] .P LETTER. .A Jacobs J. .I 200576 .U 90002660 .S Can Med Assoc J 9001; 141(8):767-70 .M Birth Rate; Developing Countries; Human; Nutrition/*. .T Third World aid [letter; comment] .P COMMENT; LETTER. .I 200577 .U 90002661 .S Can Med Assoc J 9001; 141(8):770 .M Human; Occupational Diseases/*TH; Stress, Psychological/*TH. .T Combatting occupational stress [letter; comment] .P COMMENT; LETTER. .A Yassi A; Samson K. .I 200578 .U 90002662 .S Can Med Assoc J 9001; 141(8):773-5 .M Family; Human; Kidney Transplantation/*; Tissue Donors/*. .T Kidney donation by living unrelated donors. .P JOURNAL ARTICLE. .A Blake PG; Cardella CJ. .I 200579 .U 90002663 .S Can Med Assoc J 9001; 141(8):777-80 .M Delivery of Health Care/*EC; Ethics, Medical/*; Fees and Charges; Human; Patient Compliance/*; Physician-Patient Relations. .T Ethical and economic aspects of noncompliance and overtreatment [see comments] .P JOURNAL ARTICLE. .W Physicians have an ethical responsibility for cost-saving within the current medical care delivery system. Noncompliance and overtreatment are among the causes of excessive health care expenses. An effective means of improving compliance and avoiding unwanted or fruitless treatment is improved physician-patient communication. Improved communication is also the most ethical means of avoiding these expenses. The educated participation of patients in treatment decisions and of the public in health policy formation is ethically and economically preferable to bureaucratic responses and user fees. The public must be made aware of the costs and limited benefits of medical treatments and of the effects of lifestyle on health. The medical encounter must become more supportive and educational. Medical school curricula must emphasize patient involvement, which must be reinforced to medical students and residents by staff physicians' genuine concern and effort. Quality assessments and assurance should include evaluation of communication, patient satisfaction, use of follow-up and duplication of services. .A Burgess MM. .I 200580 .U 90002664 .S Can Med Assoc J 9001; 141(8):783-90 .M Angioplasty, Transluminal; Coronary Artery Bypass; Fibrinolytic Agents/*TU; Human; Myocardial Infarction/*DT/TH; Support, Non-U.S. Gov't. .T Coronary revascularization after thrombolytic therapy for myocardial infarction: what caseloads could Canadian centres face? .P JOURNAL ARTICLE. .W A simple model was developed to project the potential effect of intravenous thrombolytic therapy on the caseloads of revascularization early after acute myocardial infarction. Published data were used to estimate the proportion of infarct patients eligible for thrombolytic treatment and their subsequent rates of percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass surgery (CABS) within 2 weeks and up to 6 to 12 weeks after treatment. Toronto regional caseload data were obtained from registries and hospital discharge records. Our primary projections, based only on coronary angiography for evidence of spontaneous or exercise-induced ischemia, suggest a 165% increase in the post-thrombolysis use of PTCA within 2 weeks of infarction and even greater increases 6 to 12 weeks after infarction. Adding in selective use of salvage PTCA for some patients with persisting pain despite thrombolysis increases the overall PTCA caseload within 2 weeks by 242%. Data on the current caseload of post-thrombolysis CABS are unavailable. However, our projected caseload for the 30% of infarct patients treated with thrombolytic drugs equals or exceeds the current number of CABS procedures performed on all infarct patients within a month of the event. All these projections are conservative, in that they consider neither procedures 3 to 12 months after infarction nor restenosis after PTCA. This analysis illustrates that current approaches to revascularization after thrombolytic therapy could have a substantial effect on PTCA and CABS caseloads. Further studies with improved caseload data are needed to validate these preliminary projections. .A Floras JS; Naylor CD; Armstrong PW. .I 200581 .U 90002665 .S Can Med Assoc J 9001; 141(8):791-5 .M Adolescence; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Ethnic Groups; Female; Hepatitis B/*EP; Human; Infant; Infant, Newborn; Male; Middle Age; Newfoundland. .T Epidemiologic features of hepatitis B virus infection in northern Labrador. .P JOURNAL ARTICLE. .W We studied the epidemiologic features of hepatitis B virus (HBV) infection in northern Labrador to determine the prevalence of the infection and to obtain a database to develop a vaccination strategy. The study population included seven communities in which five ethnic groups were represented: Inuit, Innu, mixed Inuit and European ancestry ("settler"), nonnative/nonsettler transient population ("white") and people of Innu-white or Innu-Inuit origin ("mixed"). Blood samples from 2156 people (62% of the area residents) were tested for antibody to HBV core antigen (anti-HBc), HBV surface antigen (HBsAg), HBV e antigen (HBeAg), anti-HBc IgM and antibody to the surface antigen (anti-HBs). The overall crude prevalence rate of HBV seromarkers was 14.7% and the HBsAg carrier rate at least 3.2%; the rates were highest for Inuit (26.4% and 6.9% respectively), followed by settler (10.0% and 1.9% respectively) and Innu (7.6% and 0.4% respectively); the white and mixed groups had the lowest overall rates (2.5% and 3.3% respectively). Although the overall prevalence rates were about the same for the two sexes, the HBsAg carrier rate was higher in males (male:female ratio 1.6:1.0). No HBV carriers were positive for HBeAg or anti-HBc IgM antibody. The rate of exposure to HBV was 4% for those below the age of 20 years and reached a peak for those aged 45 to 54 years (85% for Inuit, 40% for settlers and 37% for Innu). There was also a wide variation in the age-standardized prevalence rates (0% to 27.9%) among the ethnic groups in the seven communities surveyed. .A Baikie M; Ratnam S; Bryant DG; Jong M; Bokhout M. .I 200582 .U 90002666 .S Can Med Assoc J 9001; 141(8):797 .M Cardiovascular Diseases/*EP; Human; Nova Scotia; Public Health; Risk Factors. .T The public health approach: the Nova Scotia experience. Canadian Atherosclerosis Society [see comments] .P JOURNAL ARTICLE. .A MacLean DR. .I 200583 .U 90002667 .S Can Med Assoc J 9001; 141(8):807 .M American Medical Association/*; Canada; International Cooperation/*; Societies, Medical/*; United States. .T Closer cooperation between Canadian, American MDs predicted [news] .P NEWS. .A Trent B. .I 200584 .U 90002668 .S Can Med Assoc J 9001; 141(8):812-4 .M Ontario; Physicians/*SD. .T The Sioux Lookout Program: "so many problems, so few physicians". .P JOURNAL ARTICLE. .A Michaels E. .I 200585 .U 90002669 .S Can Med Assoc J 9001; 141(8):815 .M Acquired Immunodeficiency Syndrome/*ET; Blood Donors; Blood Transfusion/*; Human; Jurisprudence/*. .T Issue of transfusion-related lawsuits under study. .P JOURNAL ARTICLE. .A Moran T. .I 200586 .U 90002670 .S Can Med Assoc J 9001; 141(8):816-7 .M Microcomputers/*; Video Recording/*; Videodisc Recording/*. .T CD-ROM technology: the answer to congestive shelf failure? .P JOURNAL ARTICLE. .A Goldman B. .I 200587 .U 90002699 .S Clin Rev Allergy 9001; 7(3):233-343 .M Animal; Asthma/*; Human; Respiratory Hypersensitivity/*. .T Bronchial hyperresponsiveness. .P JOURNAL ARTICLE. .I 200588 .U 90002738 .S Cancer 9001; 64(8):1569-76 .M Adult; Aged; Colorectal Neoplasms/AN/*DI; Female; Hematoporphyrins; Human; Intestinal Mucosa/AN; Male; Middle Age; Spectrometry, Fluorescence; Support, Non-U.S. Gov't. .T Localization of hematoporphyrin. Derivative to human colorectal cancer. .P JOURNAL ARTICLE. .W This study documents the affinity of hematoporphyrin derivative (HpD) for human colorectal cancer by analysis of surface fluorescence. Ten patients undergoing elective surgery for primary colorectal cancer received intravenous HpD (2-5 mg/kg) either 3 or 72 hours preoperatively. Fluorescent photographs were taken of freshly resected specimens and analyzed using a computerized videodensitometric technique. This technique subtracted contaminating non-HpD fluorescence and facilitated estimation of HpD tissue levels. The HpD-specific fluorescence localized to tumors in all cases, and the mean HpD concentration was six-fold greater in malignant tissue than in surrounding normal mucosa (0.6 microgram/g versus 0.1 microgram/g, P less than 0.001). The authors conclude that HpD preferentially localizes to human colorectal cancer and this is relevant to the photodetection and phototherapy of colorectal neoplasia. .A Wooten RS; Ahlquist DA; Anderson RE; Carpenter HA; Pemberton JH; Cortese DA; Ilstrup DM. .I 200589 .U 90002742 .S Cancer 9001; 64(8):1595-9 .M Adolescence; Adult; Aged; Antiemetics/*TU; Cisplatin/*AE/TU; Comparative Study; Female; Human; Lorazepam/TU; Male; Methylprednisolone/TU; Middle Age; Nausea/CI/*DT; Neoplasms/*DT; Oxazepam/TU; Vomiting/PC. .T Antiemetic superiority of lorazepam over oxazepam and methylprednisolone as premedicants for patients receiving cisplatin-containing chemotherapy. .P JOURNAL ARTICLE. .W Lorazepam, oxazepam, and methylprednisolone were compared for antiemetic efficacy in patients receiving cisplatin chemotherapy. Three consecutive courses of cisplatin-containing chemotherapy were administered at equal doses so that each patient acted as his own control. Of 100 patients randomized, 85 received at least two of the three agents and were evaluable for analysis. Lorazepam significantly reduced the number of patients with more than ten vomits compared to either oxazepam (P less than 0.05) or methylprednisolone (P less than 0.001). Lorazepam also significantly reduced the number of patients with the most severe degrees of vomiting compared to either oxazepam or methylprednisolone (both P less than 0.005). The duration of vomiting was reduced significantly after the first 48 hours postchemotherapy for those patients receiving lorazepam over those receiving methylprednisolone (P less than 0.05). Lorazepam significantly reduced the number of patients with severe nausea compared to both oxazepam and methylprednisolone (both P less than 0.05), but there were no significant differences in duration of nausea among the groups. The results of linear analogue self-assessment scores indicated a strong patient preference for lorazepam over both oxazepam and methylprednisolone. Drowsiness was significantly more common with both lorazepam and oxazepam compared to methylprednisolone (both P less than 0.001). Patients who received lorazepam or oxazepam also experienced significantly more severe drowsiness than those patients receiving methylprednisolone (both P less than 0.001). Lack of recall was significantly more common with lorazepam than with oxazepam and methylprednisolone (both P less than 0.001) and was more profound when lorazepam was compared with oxazepam (P less than 0.05) and with methylprednisolone (P less than 0.001). Methylprednisolone was administered with minimal side effects. The results of this randomized cross-over study indicate that, in the dosage/schedule used, lorazepam is a significantly superior premedicant than is either oxazepam or methylprednisolone in alleviating the distress of cytotoxic-induced emesis in patients receiving cisplatin-containing chemotherapy. .A Kearsley JH; Williams AM; Fiumara AM. .I 200590 .U 90002743 .S Cancer 9001; 64(8):1600-7 .M Animal; Antibodies, Neoplasm/IM; Collagen/PD; Colorectal Neoplasms/IM/*PA; Culture Media; DNA, Neoplasm/AN; Female; Mice; Mice, Nude; Neoplasm Transplantation; Tumor Cells, Cultured/*/DE/IM. .T Tumor acquisition, propagation, and preservation. The culture of human colorectal cancer. .P JOURNAL ARTICLE. .W Fourteen new colorectal cancer cell lines were developed as part of a tumor acquisition, propagation, and preservation program for biotherapy. Fifty-six specimens were received. Nine cell lines were generated from biopsies; seven of these cell lines were from metastatic lesions. Five additional cell lines were developed from xenografts grown in nude mice. Biopsies that produced three of these xenografts gave rise to parallel culture cell lines. Biopsy-derived and xenograft-derived cell lines from the same tumor behaved similarly in culture and exhibited similar markers when assessed immunohistochemically. Collagen substrate was beneficial in the primary culture of 50% of the specimens tested. Collagen was required for the successful propagation of two cell lines. .A Lewko WM; Ladd P; Hubbard D; He YJ; Vaghmar R; Husseini S; Chang L; Moore M; Thurman GB; Oldham RK. .I 200591 .U 90002744 .S Cancer 9001; 64(8):1608-11 .M Cisplatin/TU; Combined Modality Therapy; Dysgerminoma/MO/*PA/RT/TH; Human; Male; Neoplasm Metastasis; Neoplasm Staging; Radiotherapy Dosage; Retrospective Studies; Testicular Neoplasms/MO/*PA/RT/TH. .T Testicular seminoma. Results of the Yale University experience, 1964-1984. .P JOURNAL ARTICLE. .W Eighty-three testicular seminoma patients were treated with radiation therapy from 1964 through 1984. Seventy-nine (95%) of the 83 patients had early disease that included 61 Stage I, 15 Stage IIA (pelvic or paraaortic lymph node involvement less than or equal to 5 cm), and 3 Stage IIB (pelvic or paraaortic lymph node involvement greater than 5 cm) patients. The 15-year actuarial survival for this group of Stage I and II patients was 95% (+/- 5%). Stage I patients were treated with a mean paraaortic/pelvic dose of 2924 cGy and only one patient developed recurrent disease. This recurrence was at the margin of the radiation field and probably represents a marginal miss. The Stage IIA patients were treated with slightly higher doses (mean, 3335 cGY) to the paraaortic/pelvic region and there were no recurrences. The three Stage IIB patients received tumor doses of 3245 cGy, 4090 cGy, and 4500 cGy, respectively, and there were no recurrences. Low dose prophylactic mediastinal and supraclavicular irradiation (mean, 2320 cGy) was used in 17 (94%) of the 18 Stage II patients and there were no mediastinal or supraclavicular recurrences. Four patients presented with advanced disease (one Stage III, three Stage IV) and the only disease-free survivor was treated with cisplatinum-based combination chemotherapy and radiation therapy. Three patients developed minor complications from the radiation therapy: one patient had persistent scrotal and leg edema and two patients treated with prophylactic mediastinal irradiation had chronic low leukocyte counts. Two of the 79 Stage I and II patients developed a second malignancy: one had bronchogenic carcinoma at the margin of a mediastinal field, and one had diffuse histiocytic lymphoma both in and out of the radiation therapy fields. The 15-year actuarial probability of developing a second malignancy was 3.3%. Radiation therapy after operation is a successful treatment option for most patients with Stage I and II seminoma. .A Hunter M; Peschel RE. .I 200592 .U 90002745 .S Cancer 9001; 64(8):1612-6 .M Adolescence; Adult; Aged; Biopsy/*MT; Comparative Study; Female; Human; Male; Melanoma/MO/PA/*SU; Middle Age; Skin Neoplasms/MO/PA/*SU. .T Excisional biopsy as the first therapeutic procedure versus primary wide excision of malignant melanoma. .P JOURNAL ARTICLE. .W The five-year disease-free rate (5-y-DFR) and five-year survival rate (5-y-SR) of 319 melanoma patients with a narrow excisional biopsy in local anesthesia as the first procedure followed by delayed wide excision, were compared with 5-y-DFR and 5-y-SR of 635 primary radically treated patients. Five-y-DFR and 5-y-SR did not differ in either group of patients. Furthermore, the time interval (less than or equal to 21 days versus greater than 21 days) between excisional biopsy and delayed wide excision had no influence on the outcome of the patients. Based on the results of the study and the literature, excisional biopsy of malignant melanoma followed by delayed wide excision is a safe procedure. .A Landthaler M; Braun-Falco O; Leitl A; Konz B; Holzel D. .I 200593 .U 90002746 .S Cancer 9001; 64(8):1617-9 .M Adult; Aged; Combined Modality Therapy; Female; Human; Interferon Alfa, Recombinant/AE/*TU; Male; Melanoma/PA/*TH; Middle Age; Support, Non-U.S. Gov't; Vinblastine/*TU. .T Interferon in combination with vinblastine in advanced malignant melanoma. A phase I-II study. .P JOURNAL ARTICLE. .W Nineteen patients with advanced malignant melanoma were treated with a combination of recombinant alfa-interferon (alpha-IFN) and vinblastine (VBL). The alpha-IFN was administered subcutaneously daily at an initial dose of 3 X 10(6) IU escalating to a maximal dose of 9 X 10(6) U daily for the first 10 weeks followed by 3 X/week for 6 months. The VBL was given once every week at a dose of 0.025 mg/kg. Of the 19 patients 17 were evaluable for tumor response. Thirteen patients had received chemotherapy previously. Median performance status (World Health Organization) was 0, ranging from 0 to 2. One complete response and one partial response was observed. All patients experienced flu-like symptoms attributed to alpha-IFN. Leukopenia was observed in 12 patients and a planned dose escalation of VBL was undertaken for the patients only. It is concluded that combined alpha-IFN and VBL is only marginally effective in patients with advanced malignant melanoma who have had prior chemotherapy. .A Gundersen S; Flokkmann A. .I 200594 .U 90002747 .S Cancer 9001; 64(8):1620-8 .M Adolescence; Adult; Antigens, Neoplasm/IM; Female; Human; Lymphoma/CL/*IM/PA; Lymphoma, Non-Hodgkin's/CL/*IM/PA; Male; Netherlands; T-Lymphocytes/IM. .T T-lymphoblastic and peripheral T-cell lymphomas in the northern part of The Netherlands. An immunologic study of 29 cases. .P JOURNAL ARTICLE. .W The morphologic type, immunophenotypes, and clinical presentation of 12 cases of T-lymphoblastic lymphoma and 17 cases of peripheral T-cell lymphoma were studied. The lymphoblastic cases were subclassified according to intrathymic stages of T-cell differentiation. Two cases had an early intrathymic immunophenotype (CD4-negative, CD8-negative, CD1-negative), seven cases had an intermediate intrathymic immunophenotype (CD1-positive, CD4-positive, CD8-positive), and two cases had a late intrathymic immunophenotype (CD1-positive, CD8-positive, CD4-negative); one case expressed T-cell and B-cell markers. The peripheral T-cell lymphomas were morphologically subclassified according to the updated Kiel classification. T-cell lymphomas of low-grade malignancy--chronic lymphocytic lymphoma, T-zone lymphoma, and pleomorphic small cell lymphoma--in general had a complete immunophenotype matching the immunophenotypes of normal peripheral T-cells. In addition these cases were CD38-positive and HLA class II-positive. The T-cell lymphomas of high-grade intermediate and large cell, immunoblastic and large cell anaplastic lymphoma--were characterized by loss of T-cell markers. For their establishment as T-cell lymphoma a panel of monoclonal antibodies is needed. .A Hollema H; Poppema S. .I 200595 .U 90002748 .S Cancer 9001; 64(8):1629-37 .M Antibodies, Monoclonal/DU; Brain Neoplasms/*IM; Comparative Study; Cytotoxicity, Immunologic; Glioma/*IM; Human; Interleukin-2/*PD; Killer Cells, Lymphokine-Activated/*IM; Lymphocyte Transformation/*DE; Neutrophils/IM/UL; Phenotype; Recombinant Proteins/PD; Support, Non-U.S. Gov't; T-Lymphocytes/IM. .T Interleukin-2-activated lymphocytes from brain tumor patients. A comparison of two preparations generated in vitro. .P JOURNAL ARTICLE. .W Two preparations of human recombinant interleukin-2 (rIL-2)-activated lymphocytes from patients harboring malignant brain tumors were characterized as autologous-stimulated lymphocytes (ASL) and lymphokine-activated killer (LAK) cells. ASL were generated from Ficoll-Paque-isolated, nonadherent, defibrinated peripheral blood lymphocytes (PBL) that were stimulated overnight with phytohemagglutinin (PHA) and cultured with rIL-2 (100 U/ml) for 10 days. LAK cells were produced by culturing all PBL in rIL-2 (500 U/ml) for 4 days. In 4-hour chromium release assays, LAK cells showed greater cytotoxicity than ASL against natural killer (NK)-sensitive and NK-resistant tumor cell lines; by 18 hours, the effectiveness of ASL equaled that of LAK cells. By electron microscopic study, PBL, LAK cells, and ASL showed differences. The helper/inducer to suppressor/cytotoxic ratio (T4+/T8+) of PBL, LAK cells, and ASL was 1.1:1, 1.0:1, and 0.4:1, respectively. ASL, when compared with PBL or LAK cells, have a significantly higher percentage of MO1+/DR+ and T8+/9.3+ subpopulations. ASL and LAK cells, used for the therapy of gliomas, are distinct. .A Kruse CA; Mitchell DH; Lillehei KO; Johnson SD; McCleary EL; Moore GE; Waldrop S; Mierau GW. .I 200596 .U 90002749 .S Cancer 9001; 64(8):1638-45 .M Animal; Antibodies, Monoclonal/DU; Breast Neoplasms/MO/*PA/SU; Carcinoembryonic Antigen/*AN; Cross Reactions; Human; Immunohistochemistry; Lymph Nodes/PA; Mastectomy, Simple; Mice; Mice, Inbred BALB C; Neoplasm Staging; Prognosis. .T Carcinoembryonic antigen immunocytochemistry in primary breast cancer. .P JOURNAL ARTICLE. .W We studied the immunoreactivity by immunohistology of two carcinoembryonic antigens (CEA) with specific and two CEA antibodies with nonspecific cross-reacting antigen (NCA) cross reactivity (CEA/NCA) in 180 primary breast carcinomas. Positive tissue staining was found in more than 90% of the specimens with CEA/NCA antibodies, compared with less than 30% for both CEA-specific antibodies. There was no correlation between the positivity of CEA immunocytochemistry for any of the four antibodies and histologic grade, lymph node stage, locoregional recurrence, disease-free interval (DFI), or patient survival. This large study with a long follow-up period for patients has shown that CEA and CEA/NCA immunocytochemistry have no relation to prognosis in breast cancer. An extensive review of the literature that confirms these findings should end the controversy over the place of CEA and CEA/NCA immunocytochemistry in breast cancer. .A Robertson JF; Ellis IO; Bell J; Todd JH; Robins A; Elston CW; Blamey RW. .I 200597 .U 90002750 .S Cancer 9001; 64(8):1646-51 .M Adult; Aged; Antibodies, Monoclonal/DU; Antigens, CD4/IM; Human; Immunohistochemistry; Lymphocytes/*IM/PA; Macrophages/*IM/PA; Middle Age; Spleen/*PA; Stomach Neoplasms/*IM/PA. .T Immunohistochemical assessment of splenic lymphocyte and macrophage subpopulations in patients with gastric cancer. .P JOURNAL ARTICLE. .W In order to assess the effects of malignant tumors on the immune system, 25 spleens from patients with gastric carcinoma were studied by in situ immunohistochemical methods for lymphocyte subsets and cells of the mononuclear phagocyte system. Highly significant reductions of CD4+ T cells (P less than 0.001), Ki M2+ and Ki M-3+ MPS cells (P less than 0.02 and P less than 0.05), and a stage-dependent reduction of Ki 67+ B cell proliferation activity (P less than 0.05) were seen in spleens of patients with gastric cancer. These results, which were obtained by morphologic methods in a noninvolved lymphatic organ, reflect the systemic immunosuppressive and immunodepleting effects of malignant tumors that are probably mediated by tumor-associated cytokines. .A Falk S; Seipelt G; Muller H; Stutte HJ. .I 200598 .U 90002751 .S Cancer 9001; 64(8):1652-6 .M Adult; Antigens, Neoplasm; Carcinoma, Squamous Cell/*IM/PA; Cervix Neoplasms/*IM/PA; Female; Human; Middle Age; Neoplasm Staging; Radioimmunoassay; Skin Diseases/*IM; Support, Non-U.S. Gov't; Tumor Markers, Biological/*AN. .T Elevated levels of squamous cell carcinoma antigen in patients with a benign disease of the skin. .P JOURNAL ARTICLE. .W Squamous cell carcinoma antigen (SCC), formerly referred to as TA-4, is a tumor marker for SCC of the uterine cervix. Based on the findings in a patient with complete remission after treatment for cervical carcinoma, the authors decided to analyze the sera from patients with benign dermatoses. It was found that 83% (25/30) of the patients with psoriasis and 80% (12/15) of the patients with eczema had SCC levels in excess of the cut-off value of 2.5 ng/ml. In psoriasis the serum SCC level correlated positively with the body surface area affected by the disease (r = 0.64). Seven patients with miscellaneous skin disorders, all with an inflammatory component, showed high serum SCC levels as well. Thus the existence of an inflammatory skin disease or a hyperkeratotic skin disease with an inflammatory component interferes with the usefulness of the SCC antigen as a tumor marker in SCC of the uterine cervix. .A Duk JM; van Voorst Vader PC; ten Hoor KA; Hollema H; Doeglas HM; de Bruijn HW. .I 200599 .U 90002752 .S Cancer 9001; 64(8):1657-64 .M Adenocarcinoma/*GE/PA; Adult; Aged; Aged, 80 and over; Aneuploidy; Cell Nucleus/PA; DNA, Neoplasm/*AN; Female; Flow Cytometry; Human; Lung Neoplasms/*GE/PA; Male; Middle Age; Neoplasm Staging. .T DNA cytofluorometric and nuclear morphometric analyses of lung adenocarcinoma. .P JOURNAL ARTICLE. .W The nuclear DNA content of tumor cells in imprint smears prepared from 72 surgically resected adenocarcinomas of the lung was determined prospectively by means of cytofluorometry, and its relationship to pathologic stage, degree of histologic differentiation, and nuclear atypia represented by the mean nuclear area (MNA) and standard deviation of the nuclear area (SDNA) was studied. The mean nuclear DNA content (MNDC) of poorly differentiated adenocarcinomas was significantly larger than that of well-differentiated adenocarcinomas both in Stages I + II and III + IV (P less than 0.001, each), and the MNDC of Stages III + IV was significantly larger than that of I + II in poorly differentiated adenocarcinomas (P less than 0.01). There was a tendency for histogram Patterns III and IV, in which more aneuploid cells were present than in I and II, to be more common and for the incidence of the aneuploid stem cell line to be higher in less differentiated and more advanced adenocarcinomas, although the differences were not significant statistically. Furthermore, there were significant positive correlations between MNDC and MNA (P less than 0.01) and between MNDC and SDNA (P less than 0.05). The averages of the MNA according to the histogram pattern increased significantly in the increasing order of Patterns I to IV. These results indicate that the nuclear DNA content increases in less differentiated and more advanced adenocarcinomas, and that the nuclear atypia is reflected in abnormal nuclear DNA content (DNA aneuploidy). .A Asamura H; Nakajima T; Mukai K; Noguchi M; Shimosato Y. .I 200600 .U 90002753 .S Cancer 9001; 64(8):1665-8 .M Bromodeoxyuridine/*DU; Cell Division; Endoscopy; Gastrectomy; Human; Lymphatic Metastasis; Stomach Neoplasms/*PA/SU; Tumor Cells, Cultured/PA. .T Proliferative activity of early gastric cancer measured by in vitro and in vivo bromodeoxyuridine labeling. .P JOURNAL ARTICLE. .W Forty seven patients with early gastric cancer received a 30-minute intravenous injection of bromodeoxyuridine (BrdU), 1000 mg each 1 hour before laparotomy, to label tumor cells in the S phase. In 13 of 47 patients, specimens obtained by endoscopic biopsy were cultured in vitro at 37 degrees C for 1 hour under three times the atmospheric pressure in a vial with 400 microM BrdU. Labeled cells were detected in the resected specimen and the cultured specimen by immunohistochemical staining procedure. The BrdU labeling index (LI, defined as the percentage of labeled cells in relation to the 1000 tumor cells) was calculated for each specimen. All patients without lymph node metastasis had an in vivo BrdU LI of less than 12%. In contrast, 31% of patients with early gastric cancer with an in vivo BrdU LI greater than 12% had lymph node metastasis. There was a correlation between the in vivo and the in vitro LI. Therefore, the in vitro BrdU LI of specimens obtained by endoscopic biopsy may be a useful indicator of lymph node status in patients with individual early gastric cancers before operations. If the in vitro BrdU LI is less than 12% lymph node dissection may not be necessary. .A Kamata T; Yonemura Y; Sugiyama K; Ooyama S; Kosaka T; Yamaguchi A; Miwa K; Miyazaki I. .I 200601 .U 90002754 .S Cancer 9001; 64(8):1669-73 .M Adult; Aged; Aneuploidy; Diploidy; DNA, Neoplasm/*AN; Female; Human; Kidney Neoplasms/*GE/PA; Male; Middle Age; Neoplasm Metastasis; Prognosis; Support, Non-U.S. Gov't. .T Prognostic significance of the DNA content of renal carcinoma. .P JOURNAL ARTICLE. .W DNA analysis was performed on fresh frozen samples of the primary tumor in 32 patients with renal carcinoma (13 with apparently localized disease and 19 with metastases at presentation). A comparison of ploidy with staging and standard histologic variables was performed. None of the patients who presented without metastases died of disease during the follow-up period. Eleven of 13 patients of this group had a diploid/near diploid pattern, and metastases developed in only one patient. Patients with metastatic disease and a diploid/near diploid DNA content had a significantly better survival rate than those with aneuploid primary tumors. Statistical analysis showed that grade and ploidy contributed significant but independent prognostic information. We concluded that DNA content is a useful prognostic factor in renal carcinoma. .A deKernion JB; Mukamel E; Ritchie AW; Blyth B; Hannah J; Bohman R. .I 200602 .U 90002755 .S Cancer 9001; 64(8):1674-81 .M Adult; Aged; Antibodies, Monoclonal/DU; Antigens, Tumor-Associated, Carbohydrate/*BL; Breast Neoplasms/*BL/MO/PA; Carcinoembryonic Antigen/*BL; Female; Human; Male; Middle Age; Neoplasm Metastasis/*; Radioimmunoassay; Tumor Markers, Biological/BL. .T Circulating tumor marker levels in advanced breast carcinoma correlate with the extent of metastatic disease. .P JOURNAL ARTICLE. .W The importance of the extent of metastatic disease in the circulating levels of CA 15-3 and carcinoembryonic antigens (CEA) was studied in 173 patients with advanced breast carcinoma. Estimates of the extent of metastatic disease were obtained by an objective arbitrary scale. Patients were observed clinically after serum samples were obtained, and survival was recorded. Elevated values of CA 15-3 (greater than 40 U/ml) were seen in 130 patients and CEA values (greater than 5 ng/ml) in 97 cases (75% versus 56%, P less than .0001). Elevated CA 15-3 values correlated with the estimated extent of metastatic disease (P less than .0001), number of metastases (P = .0006), and survival from study entry (P = .01). Elevated CEA values correlated with extent of disease (P less than .0001), but not with the number of metastases or with survival. No correlation was found between the elevated values of CA 15-3 or CEA and age, menopausal status, and initial tumor size or nodal status. The combination of the elevated values of CA 15-3 and CEA was more sensitive than CA 15-3 alone (P = .04), but there were no significant improvements when subgroups were considered. Significant differences, that depended on which specific organ was affected dominantly by metastases, were seen in the mean levels of CA 15-3 antigen. Similarly, patients with liver involvement had higher mean levels of CA 15-3 than those without hepatic metastases. A stepwise regression analysis of the dominant site of metastases, liver involvement, and estimated extent of disease showed that only the latter parameter retained a significant correlation with CA 15-3 antigen levels (P less than .0001). Median survival of patients who showed abnormal CA 15-3 levels was significantly shorter than that of patients with nonelevated CA 15-3 (10.1 versus 18.0 months, P = .04). This difference was not appreciated with CEA levels (10.2 versus 12.2 months, P = .4). We conclude that tumor marker levels in patients with advanced breast carcinoma correlate with the extent of metastatic disease. In addition, the CA 15-3 assay is more sensitive and correlates more accurately with the extent of disease than CEA. Finally, the observed CA 15-3 differences by organ involvement are related to the extent of disease variations. The objective evaluation of the extent of metastatic disease provides a new approach in the study and comparison of breast cancer-associated tumor markers. .A Colomer R; Ruibal A; Salvador L. .I 200603 .U 90002756 .S Cancer 9001; 64(8):1682-5 .M Antineoplastic Agents, Combined/TU; B-Lymphocytes; Bleomycins/AD; Case Report; Cyclophosphamide/AD; Doxorubicin/AD; Eosinophilia/*CO/PA; Human; Immunohistochemistry; Leucovorin/AD; Lymph Nodes/PA; Lymphoma, Non-Hodgkin's/*CO/DT/PA; Male; Methotrexate/AD; Middle Age; Prednisone/AD; Vincristine/AD. .T B-cell lymphoma associated with eosinophilia. .P JOURNAL ARTICLE. .W A case of non-Hodgkin's lymphoma associated with eosinophilia is reported. The lymphoma was of the diffuse, large-cell type and was of B-cell origin. The number of eosinophils decreased with combination chemotherapy, along with a reduction in the size of the lymph nodes. Eosinophilia reappeared with the regrowth of lymphoma. The relationship between B-cell lymphoma and eosinophilia is discussed. .A Watanabe K; Shinbo T; Kojima M; Naito M; Tanahashi N; Nara M. .I 200604 .U 90002757 .S Cancer 9001; 64(8):1686-93 .M Adolescence; Anaplasia; Chi-Square Distribution; Female; Hodgkin's Disease/CL/MO/*PA; Human; Lymphocyte Depletion; Male; Neoplasm Staging; Recurrence. .T Relationship of histopathologic features to survival and relapse in nodular sclerosing Hodgkin's disease. A study of 1659 patients. .P JOURNAL ARTICLE. .W Nodular sclerosing (NS) Hodgkin's disease (HD) with extensive areas of lymphocyte depletion or with numerous anaplastic Hodgkin's cells, termed Grade II NS, is associated with a poor response to initial therapy, an increased relapse rate, and decreased survival when compared with other NS variants, termed Grade I NS. The histopathologic subdivision of NS HD into Grade I and Grade II is easy to perform and provides essential prognostic information that is independent of stage. Patients with Grade II NS HD may require more aggressive initial therapy if their survival is to be improved. .A MacLennan KA; Bennett MH; Tu A; Hudson BV; Easterling MJ; Hudson GV; Jelliffe AM. .I 200605 .U 90002761 .S Cancer 9001; 64(8):1714-6 .M Aged; Blood Cell Count; Case Report; Female; Human; Hypothalamic Neoplasms/*PA/RA; Leukemia, Lymphocytic, Chronic/*PA; Tomography, X-Ray Computed. .T Chronic lymphocytic leukemia with hypothalamic invasion. .P JOURNAL ARTICLE. .W Headaches and a state of confusion developed in a patient with chronic lymphocytic leukemia (CLL). A computed tomography (CT) scan of the head showed a hyperdense lesion in the hypothalamus with obstruction of the foramina of Monro. Leukemic cells with monoclonal lambda B-cell markers were identified in the ventricular fluid at the time of surgical decompression. Similar cells were identified in the peripheral blood. This lesion has not been described as a complication of CLL, a disease that, unlike other leukemias, rarely has central nervous system manifestations. .A Garofalo M Jr; Murali R; Halperin I; Magardician K; Moussouris HF; Masdeu JC. .I 200606 .U 90002763 .S Cancer 9001; 64(8):1720-6 .M Adult; Antineoplastic Agents, Combined/TU; Bone Marrow/PA; Case Report; Diagnosis, Differential; Female; Hodgkin's Disease/*DI/DT/PA; Human; Male; Mechlorethamine/AD; Myelofibrosis/*DI/PA; Prednisone/AD; Procarbazine/AD; Vincristine/AD. .T Hodgkin's disease presenting as myelofibrosis. .P JOURNAL ARTICLE. .W Four patients with Hodgkin's disease and bone marrow fibrosis are presented in whom the clinical presentation was dominated by cytopenias; this was associated with a delayed diagnosis for an average of 20 months. Despite marrow involvement, chemotherapy resulted in complete remissions and two patients appear to have been cured. Marrow fibrosis resolved at least partially after chemotherapy. The medical literature relevant to bone marrow involvement by Hodgkin's disease is reviewed. Hodgkin's disease should be considered in the differential diagnosis of idiopathic myelofibrosis. .A Meadows LM; Rosse WR; Moore JO; Crawford J; Laszlo J; Kaufman RE. .I 200607 .U 90002764 .S Cancer 9001; 64(8):1727-37 .M Adolescence; Adult; Alkaline Phosphatase/BL; Blood Transfusion/*; Bone Neoplasms/MO/*TH; Child; Child, Preschool; Combined Modality Therapy; Comparative Study; Female; Human; Male; Middle Age; Osteosarcoma/MO/*TH; Prognosis; Retrospective Studies. .T Effect of perioperative transfusions on survival in osteosarcoma treated by multimodal therapy. .P JOURNAL ARTICLE. .W We report on a retrospective study of 155 patients amputated for nonmetastatic osteosarcoma of the long bones. Among the various prognostic variables considered, a significant correlation was found only between survival and transfusions. In this report, the authors consider some hypotheses reported by others for tumors of a different nature and site and conclude that perioperative transfusion may induce depression in the immune response, which is the cause of a shorter survival in the patients reviewed. .A Chesi R; Cazzola A; Bacci G; Borghi B; Balladelli A; Urso G. .I 200608 .U 90002765 .S Cancer 9001; 64(8):1738-42 .M Adolescence; Antineoplastic Agents, Combined/TU; Case Report; Combined Modality Therapy; Cyclophosphamide/AD; Doxorubicin/AD; Ganglioneuroma/*PA/TH; Human; Lymph Node Excision; Male; Microscopy, Electron; Myelin Sheath/*PA; Neoplasms, Multiple Primary/*; Orchiectomy; Peripheral Nerve Neoplasms/*PA/TH; Testicular Neoplasms/*PA/TH; Vincristine/AD. .T A malignant peripheral nerve sheath tumor in association with a paratesticular ganglioneuroma. .P JOURNAL ARTICLE. .W A malignant peripheral nerve sheath (PNS) tumor and a benign ganglioneuroma were present as a composite tumor in the paratesticular area of a 15-year-old boy. The pathologic diagnosis was made by characteristic histologic and ultrastructural features and was supported by the demonstration of neuron-specific enolase (NSE)-positive ganglion cells and S-100-protein-positive spindle cells consistent with schwannian cells. The patient has remained disease-free for 3 years since the orchiectomy and the retroperitoneal lymph node dissection, which was followed by combination chemotherapy. .A Banks E; Yum M; Brodhecker C; Goheen M. .I 200609 .U 90002766 .S Cancer 9001; 64(8):1743-6 .M Antineoplastic Agents/TU; Human; Lymph Node Excision; Lymphatic Metastasis; Male; Prognosis; Prostatic Neoplasms/MO/*PA/RT/TH. .T Prognosis in stage D-1 prostate cancer relative to anatomic sites of nodal metastases. National Prostatic Cancer Treatment Group. .P JOURNAL ARTICLE. .W The investigators of the National Prostatic Cancer Treatment Group (NPCTG) have entered 212 patients with surgically confirmed stage D-1 prostate cancer in studies to determine the efficacy of adjuvant therapy after either definitive surgery (Protocol 900) or definitive radiotherapy (Protocol 1000). Follow-up indicates that this group represents 70% of all patients with recurrent disease. Because patients with less than 20% nodal involvement were found to have a statistically significant better progression-free-survival (PFS) than those with greater than 20% nodal involvement, we examined the exact anatomic sites of nodal metastases. The status of obturator, external iliac, internal iliac, and common iliac nodes was compared to PFS and overall survival in 198 patients with D-1 disease in both protocols. Results demonstrate no significant difference in either PFS or overall survival relative to anatomic sites of positive nodes. These data suggest that although minimal pelvic nodal metastasis is consistent with improved PFS, there is no predictable anatomic distribution of disease consonant with that better prognosis. .A Schmidt JD; Gibbons RP; Bartolucci A; Murphy GP. .I 200610 .U 90002767 .S Cancer 9001; 64(8):1747-52 .M Acute Disease; Adolescence; Adult; Aged; Catheterization, Central Venous/*AE; Catheters, Indwelling/*AE; Comparative Study; Female; Human; Leukemia/*DT; Leukopenia/CO; Lymphoma, Non-Hodgkin's/*DT; Male; Middle Age; Staphylococcal Infections/*ET. .T Complications from long-term indwelling central venous catheters in hematologic patients with special reference to infection. .P JOURNAL ARTICLE. .W Forty-three evaluable patients with hematologic malignancies, mainly acute leukemia, were prospectively randomized to receive a double lumen central venous catheter or a totally implantable venous access system. The mean catheter stay was 166 days (median, 104 days) for the 23 double lumen catheters and 164 days (median, 65 days) for implanted systems. Exit site infections were not encountered in double lumen catheters, but there were two proven infections around the injection port of implanted devices. Tunnel infections did not occur. Seven double lumen catheters and four implanted systems were removed because of infection. Staphylococcus epidermidis was the predominant microorganism cultured from these catheters. Five of nine patients with double lumen catheters and catheter-related S. epidermidis infection and the two patients with implanted systems in whom S. epidermidis was cultured were on selective gut decontamination. The pattern of infection did not seem to be influenced by this regimen. Totally implantable systems proved to be as safe as double lumen central venous lines. .A Kappers-Klunne MC; Degener JE; Stijnen T; Abels J. .I 200611 .U 90002769 .S Cancer 9001; 64(8):1758-63 .M Adolescence; Caucasoid Race; Child; Child, Preschool; China/EH; Female; Hawaii; Human; Infant; Japan/EH; Male; Neoplasms/*EH/EP; Philippines/EH; Support, U.S. Gov't, P.H.S.. .T Ethnic patterns of childhood cancer in Hawaii between 1960 and 1984. .P JOURNAL ARTICLE. .W Cases of childhood cancer (less than 15 years of age at diagnosis), diagnosed between 1960 and 1984, were obtained from the Hawaii Tumor Registry, a population-based Surveillance, Epidemiology, and End Results (SEER) participant covering the entire State of Hawaii. During the 25 years of data collection, cancer was diagnosed in 398 males and 302 females, with overall age-adjusted incidence rates of 140.5 and 112.2 per million, respectively. Leukemia was the leading cause of childhood cancer, accounting for over 1/3 of diagnoses during the study period. Standardized incidence ratios (SIR) were calculated for each ethnic-sex group separately based on US white age-specific incidence rates for 1973 to 1982 from the SEER program. Overall, incidence rates for childhood cancer in Hawaii were generally similar to those found in all SEER areas. .A Goodman MT; Yoshizawa CN; Kolonel LN. .I 200612 .U 90002770 .S Cancer 9001; 64(8):1764-8 .M Breast Neoplasms/EP/*ET/MO; Canada; Female; Germany, West; Great Britain; Human; Italy; Lung Neoplasms/EP/*ET/MO; Male; Support, Non-U.S. Gov't; Tobacco Smoke Pollution/*AE; USSR. .T Associations between data for male lung cancer and female breast cancer within five countries. .P JOURNAL ARTICLE. .W Mainly on the basis of associations noted between international rates of male lung cancer and female breast cancer, passive smoking has been suggested recently as a major risk factor for female breast cancer. In this report, the authors describe the associations between data for female breast cancer and male lung cancer within five countries. For one country (Scotland) the authors examined the mortality rates of these cancers over time, and their relationship to trends for tobacco consumption. The correlations between female breast cancer and male lung cancer were significantly positive in Italy, USSR, and West Germany, weakly positive in Canada, absent in Scotland, and significantly negative in England and Wales. In Scotland, the mortality rates of these cancers over time were significantly correlated. There was a clear relationship between male lung cancer and tobacco consumption, but only a weak relationship between female breast cancer and tobacco consumption. .A Williams FL; Lloyd OL. .I 200613 .U 90002772 .S Cancer 9001; 64(9):1777-82 .M Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Combined/*TU; Bleomycins/AD; Carcinoma, Squamous Cell/RT/*TH; Cisplatin/AD; Combined Modality Therapy/AE; Esophageal Neoplasms/RT/*TH; Female; Heat/*TU; Human; Male; Microwaves/*TU; Middle Age; Prognosis. .T Thermo-chemo-radiotherapy of esophageal cancer. A preliminary report of 34 cases. .P JOURNAL ARTICLE. .W Thirty-four cases of esophageal cancer were treated by radiation combined with chemotherapy and hyperthermia (triple therapy) from September 1985 to January 1986. Hyperthermia was performed by an intracavitary microwave applicator of 915 MHz. The temperature at the tumor margin was 43 degrees C to 44 degrees C, whereas at the middle luminal surface of tumor it reached at 44 degrees C to 48.5 degrees C. Chemotherapy was with bleomycin (PYM) 20 mg/session, intramuscularly (IM) and cisplatin (DDP) 1.0 to 1.5 mg/kg/session intravenously (IV). Hyperthermia and chemotherapy were given simultaneously within 30 minutes after 500 cGy of radiation. Three modalities were given on the same day once a week for six sessions. The total response rate (complete + partial response [CR + PR]) was 94% (32/34) and 1-year and 2-year survival rates were 74% (25/34) and 44% (15/34), respectively. Among them were 23 patients primarily treated by triple therapy with the 1-year and 2-year survival rates of 83% (19/23) and 48% (11/23), respectively. No serious side effects were seen. The average microwave power consumption during the hyperthermic treatment and its prognostic significance are discussed. .A Hou BS; Xiong QB; Li DJ. .I 200614 .U 90002773 .S Cancer 9001; 64(9):1783-9 .M Adenocarcinoma/DT/RT/*SC; Blood Chemical Analysis; Colorectal Neoplasms/PA; Combined Modality Therapy/AE; Female; Fluorouracil/AD/*TU; Hepatic Artery/*; Human; Infusions, Intra-Arterial; Liver Neoplasms/DT/RT/*SC; Male; Middle Age; Random Allocation; Support, U.S. Gov't, P.H.S.; Survival Analysis. .T Combined hepatic artery 5-fluorouracil and irradiation of liver metastases. A randomized study. .P JOURNAL ARTICLE. .W The effect of hepatic irradiation (RT) after intraarterial 5-fluorouracil (5-FU) was evaluated in 37 randomized patients with colorectal adenocarcinoma hepatic metastases. Patients underwent percutaneous transbrachial artery catheterization of the hepatic artery followed by 21-day continuous 5-FU infusion (CT). Hepatic irradiation of 25.5 Gy was delivered to 19 patients 14 days after completion of infusion (CT + RT). All patients received subsequent weekly maintenance 5-FU. A 37% (seven of 19) response rate was observed in CT + RT, and a 50% response rate (nine of 18) in CT: median survival was 6 months for CT + RT, and 8 months for CT, (P = 0.106). Improved survival was observed in two subsets of patients. Tumor vascularity was graded angiographically from 0 to 4+; those patients with highest vascularity (4+) had a 20-month median survival (P = 0.0009). Patients with Grade 1, well-differentiated, histologic type had a median survival of 20 months (P = 0.0001). Four patients with both 4+ vascularity and Grade 1 histologic type had 27.5 months' median survival (P = 0.0019). Age, performance status, elevated liver function tests, previous systemic therapy, and time interval between diagnosis and entry on this study did not impact on survival (P greater than 0.05), nor did these variables eliminate the significance of vascularity and grade (P less than 0.05). Survival after intraarterial 5-FU infusion was not improved by this regimen of sequential external irradiation. Regional therapy may benefit those patients with 4+ vascular tumors and/or well-differentiated tumor grade. Future trials are needed to explore the interaction of halogenated pyrimidines with irradiation and determine whether these prognostic factors can aid in patient selection for regional therapy of hepatic metastases. .A Wiley AL Jr; Wirtanen GW; Stephenson JA; Ramirez G; Demets D; Lee JW. .I 200615 .U 90002776 .S Cancer 9001; 64(9):1805-11 .M Aged; Antineoplastic Agents, Combined; Blood Chemical Analysis; Female; Human; Male; Metabolic Clearance Rate; Middle Age; Neoplasms/*DT; Nifedipine/AD/*TU; Radioimmunoassay; Regression Analysis; Support, Non-U.S. Gov't; Vincristine/AD/AE/*PK. .T Pharmacokinetics of vincristine in cancer patients treated with nifedipine. .P JOURNAL ARTICLE. .W The pharmacokinetics of vincristine (VCR) after an intravenous bolus dose of 2 mg were studied in patients with cancer with and without a concomitant treatment with the calcium-entry blocker nifedipine (NIF). VCR concentrations were determined by a sensitive radioimmunoassay. Pharmacokinetic data were analyzed by a nonlinear weighted least-square regression program (SAS-NLIN). A tri-exponential model fitted the raw data better than a bi-exponential model in five of 14 (35%) patients treated with VCR alone and in seven of 12 (58%) patients treated with VCR plus NIF (P = NS). The T1/2 alpha was shorter in NIF-treated patients, whereas the T1/2 gamma was longer in the NIF-treated group. The NIF-treated group showed an increase in the AUC O-infinity and AUC 1 to 96 hours, and a decrease in the AUC 0 to 1 hour. Total plasma clearance of VCR and 7-day urinary excretion of VCR was reduced in the NIF-treated patients. These data suggest that, when VCR is administered to NIF-treated patients with cancer, there is a decrease in VCR clearance from the body. Theoretically, a greater cytotoxicity may be anticipated. .A Fedeli L; Colozza M; Boschetti E; Sabalich I; Aristei C; Guerciolini R; Del Favero A; Rossetti R; Tonato M; Rambotti P; et al. .I 200616 .U 90002777 .S Cancer 9001; 64(9):1812-8 .M Adolescence; Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Combined/*TU; Cytarabine/AD/*TU; Doxorubicin/AD; Female; Human; Infusions, Intravenous; Injections, Subcutaneous; Male; Middle Age; Myelodysplastic Syndromes/BL/*DT/PA; Remission Induction; Survival Analysis; Thioguanine/AD. .T The role of low-dose cytosine arabinoside and aggressive chemotherapy in advanced myelodysplastic syndromes. .P JOURNAL ARTICLE. .W The efficacy of low-dose cytosine arabinoside (Ara-C) and aggressive chemotherapy was assessed in 67 patients with advanced myelodysplastic syndromes (MDS). In most cases, treatment was started because of worsening peripheral cytopenia, increase in bone marrow blasts, or transition of MDS to acute myeloid leukemia (AML). Of 51 patients (age range, 18-82 years) receiving low-dose Ara-C by subcutaneous bolus injection (10 mg/m2 every 12 hours) or continuous intravenous infusion (20 mg/m2/day), nine (18%) entered complete remission (CR) and four (8%) had a partial response (PR). Duration of CR varied from 4 to 25+ months. Overall survival of patients treated with Ara-C was not superior to that of a historical control receiving supportive care only. Hematologic toxicity of low-dose Ara-C was considerable, with 12 patients (24%) dying of hemorrhage or infection during the initial treatment course. Sixteen patients (age range, 17-65 years) who presented with a Karnofsky score of more than 80% were chosen for aggressive chemotherapy using standard AML protocols. In this group, nine CR and two PR were obtained. Early death from pneumonia occurred in two patients, and three patients had refractory disease. The factors most strongly associated with successful remission induction were (1) presence of Auer rods in granulocyte precursors, and (2) a comparatively low medullary blast count (less than 30%) at the start of treatment. Median duration of bone marrow aplasia for patients entering CR was 21 days (range, 6-51). Prolonged remissions (22+, 27+, and 29 months, respectively) could be achieved in three of four patients receiving consolidation and maintenance chemotherapy after induction of CR. From these data we conclude that aggressive chemotherapy should not generally be considered contraindicated in advanced MDS. In patients with a good Karnofsky score, this form of treatment may be more advantageous than the currently favored low-dose Ara-C, which is also myelotoxic, but induces remissions in only a minority of patients. .A Aul C; Schneider W. .I 200617 .U 90002778 .S Cancer 9001; 64(9):1819-23 .M Aged; Antineoplastic Agents, Combined/*TU; Breast Neoplasms/*DT/ME/MO; Combined Modality Therapy; Cyclophosphamide/AD; Female; Fluorouracil/AD; Human; Mastectomy, Modified Radical; Menopause/*; Methotrexate/AD; Middle Age; Neoplasm Recurrence, Local/PC; Prednisone/AD; Receptors, Estrogen/*AN; Support, U.S. Gov't, P.H.S.; Survival Analysis; Tamoxifen/AD/*TU; Vincristine/AD. .T Endocrine versus endocrine plus five-drug chemotherapy in postmenopausal women with stage II estrogen receptor-positive breast cancer. .P JOURNAL ARTICLE. .W Postmenopausal women who underwent modified radical mastectomy for Stage II, estrogen receptor (ER)-positive breast cancer were randomized to receive endocrine treatment (tamoxifen [T], 40 mg daily for 3 years) alone versus endocrine treatment plus five-drug chemotherapy (Cytoxan [cyclophosphamide, C], methotrexate [M], 5-fluorouracil [F], vincristine [V], and prednisone [P], CMFVP, for 1 year). Chemotherapy consisted of oral P (1 month), oral C (12 months), and intravenous MFV weekly for the first 3 months, biweekly for 3 months, and triweekly for 6 months. Patients were entered into the study from October 1979, to October 1985, and the median follow-up is 55 months. Results show that with 94 postmenopausal women, disease-free survival (DFS) is significantly greater (P = 0.04, log-rank test; P = 0.03, multivariate analysis) in patients receiving CMFVPT as compared to those receiving T alone. These results suggest that intensive chemotherapy combined with T is more effective in delaying recurrence than T alone in postmenopausal patients. .A Pearson OH; Hubay CA; Gordon NH; Marshall JS; Crowe JP; Arafah BM; McGuire W. .I 200618 .U 90002779 .S Cancer 9001; 64(9):1824-8 .M Adult; Antineoplastic Agents, Combined/AE/*TU; Cisplatin/AD; Dactinomycin/AD; Etoposide/AD; Female; Human; Neoplasm Recurrence, Local/DT; Parity; Pregnancy; Prognosis; Remission Induction; Trophoblastic Tumor/BL/*DT/SC; Uterine Neoplasms/BL/*DT. .T Treatment of high-risk gestational trophoblastic disease with chemotherapy combinations containing cisplatin and etoposide. .P JOURNAL ARTICLE. .W The authors have treated 22 patients with high-risk gestational trophoblastic disease (GTD) by cisplatin-etoposide-containing combinations. Sixteen patients were treated with dactinomycin, platinum, and etoposide combination (APE regimen) and six patients had platinum and etoposide combination (PE regimen). Fourteen patients were treated for resistant or relapsing GTD after first-line therapy, and eight patients initially. All 22 patients were high risk according to the World Health Organization prognostic score values. Sustained complete remission was achieved in 19 patients (86%). All eight patients who received treatment as initial therapy were cured (100%) whereas only 11 patients were cured among the 14 patients who failed prior chemotherapy (78%). Hematologic and renal toxicities were limited and no treatment-related deaths occurred in this group of patients. Cisplatin and etoposide could be more widely used in chemotherapeutic combinations for high-risk gestational trophoblastic disease. .A Theodore C; Azab M; Droz JP; Assouline A; George M; Piot G; Bellet D; Michel G; Amiel JL. .I 200619 .U 90002780 .S Cancer 9001; 64(9):1829-32 .M Adult; Antineoplastic Agents, Combined/AE/*TU; Bleomycins/AD; Brain Neoplasms/RT/SC; Cisplatin/AD; Combined Modality Therapy; Female; Human; Hysterectomy; Pregnancy; Remission Induction; Trophoblastic Tumor/*DT/SC; Uterine Neoplasms/*DT; Vinblastine/AD. .T Cisplatin, vinblastine, and bleomycin combination in the treatment of resistant high-risk gestational trophoblastic tumors. .P JOURNAL ARTICLE. .W Eight patients with high-risk gestational trophoblastic tumors (GTT) resistant to multiagent chemotherapy were treated with the combination of cisplatin, vinblastine, and bleomycin (PVB). All patients had a metastatic disease including three patients with two metastatic sites and two patients with brain metastases. Four patients achieved complete remission (CR) with the PVB regimen (50%). Three additional patients had partial remission (PR) of whom two were converted into CR by surgery of resistant residual lesions. One patient relapsed and the remaining five patients in CR were cured (62%). A multimodal approach was necessary in most patients as five of them had hysterectomy and two patients had a whole-brain irradiation. Toxicity was mild with no treatment related deaths. .A Azab M; Droz JP; Theodore C; Wolff JP; Amiel JL. .I 200620 .U 90002781 .S Cancer 9001; 64(9):1833-7 .M Adenocarcinoma/PA/*RT/SU; Adult; Aged; Brachytherapy; Carcinoma, Squamous Cell/PA/*RT/SU; Combined Modality Therapy; Esophageal Neoplasms/PA/*RT/SU; Esophagus/*PA; Female; Human; Lymphatic Metastasis; Male; Middle Age; Neoplasm Invasiveness; Pilot Projects; Radiotherapy Dosage. .T Pathologic findings in total esophagectomy specimens after intracavitary and external-beam radiotherapy. .P JOURNAL ARTICLE. .W Pathologic findings in 21 esophagectomy specimens from patients having preoperative combined intracavitary radiotherapy (ICR) and external-beam radiotherapy (EBR) are described. Eleven patients received 1500 cGY ICR and 4000 cGy EBR (Group 1) and ten patients received 1500 cGy plus 2000 to 3000 cGy EBR (Group 2). Effectiveness of radiotherapy was expressed as the ratio between depth of radiation effect and depth of tumor invasion. Depth was expressed as one of four levels: Level I, not deeper than the muscularis mucosa; Level 2, involving but not deeper than submucosa; Level 3, involving but not deeper than muscularis propria; and Level 4, involving periesophageal soft tissue. The depth of radiation damage to tumor cells was comparable between the two groups. However, residual tumor was present in the periesophageal tissue in only one of 11 patients after high-dose EBR compared to of ten patients with lower dose EBR (P less than 0.01, chi-square test). A ratio of one between radiation effect and depth of tumor invasion was present in six patients receiving high-dose EBR and one patient receiving lower dose EBR (P less than 0.05). The authors conclude that ICR combined with EBR affords good local tumor control in the majority of patients. Higher doses of EBR give a better radiation effect in deeper layers of the esophageal wall. The ratio between depth of radiation effect and tumor invasion provides a simple and objective approach to the pathologic analysis of esophagectomy specimens. .A Berry B; Miller RR; Luoma A; Nelems B; Hay J; Flores AD. .I 200621 .U 90002782 .S Cancer 9001; 64(9):1838-42 .M Biopsy; Carcinoma/*PA; Endoscopy; False Positive Reactions; Fiber Optics/*; Human; Nasopharyngeal Neoplasms/*PA; Neoplasm Invasiveness; Neoplasm Staging; Prospective Studies; Support, Non-U.S. Gov't. .T Fiberoptic endoscopic examination and biopsy in determining the extent of nasopharyngeal carcinoma. .P JOURNAL ARTICLE. .W This is a prospective study on the use of flexible endoscope and multiple biopsies in the assessment of nasopharyngeal carcinoma in 72 patients. This study confirmed the presence of submucosal growth pattern in nasopharyngeal carcinoma in 72 patients. This study confirmed the presence of submucosal growth pattern in nasopharyngeal carcinoma and this occurred in 13.8% of patients. Occult microscopic extension of tumor not detectable by fiberoptic endoscopy occurred in another 51.4% of patients. It has also been shown that multiple biopsy is superior to clinical examination in evaluating the extent of disease in nasopharyngeal carcinoma. Multiple biopsies are suggested for the early detection of nasopharyngeal carcinoma in high-risk cases. Although the better-defined tumor extent do not currently influence the treatment policy of nasopharyngeal carcinoma, and it is too early to assess its prognostic significance, it betters our understanding of the behavior of this tumor. Future analysis in correlation with long-term follow-up data may help to improve the stage classification systems and treatment strategy. .A Sham JS; Wei WI; Kwan WH; Chan CW; Choi PH; Choy D. .I 200622 .U 90002783 .S Cancer 9001; 64(9):1843-7 .M Aged; Body Weight/RE; Cholecystectomy; Combined Modality Therapy; Dyspepsia/ET; Female; Gallbladder Neoplasms/PA/*RT/SU; Human; Middle Age; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Postoperative Care/*; Prospective Studies; Radiotherapy/AE. .T Primary carcinoma of the gallbladder. Adjuvant postoperative external irradiation. .P JOURNAL ARTICLE. .W Seven patients received the same postoperative (Postop) external-beam irradiation (NRT) after apparent complete removal of gallbladder carcinoma between August 1983 to February 1988. A dosage of 4600 cGy were delivered on a first volume (average treated volume 0.87 liters) corresponding to this of potentially locoregional disease, completed by a boost dose of 900 cGy on the gallbladder bed. Moderate acute side effects were seen in five patients; regressive dyspepsia in three and mean weight loss of 1.5 kg in three. The minimum follow-up is 5 months and the maximum is 58 months. Five patients are alive with no evidence of disease (NED) after 5, 9, 11, 31, and 58 months, respectively. One died at 12 months with local recurrence, liver metastasis, and peritoneal implants. Another one died at 26 months of abdominal recurrence. With regard to the natural history of this tumor, the dismal results obtained by surgery alone, and our preliminary data, we advocate Postop adjuvant XRT as a safe treatment. .A Bosset JF; Mantion G; Gillet M; Pelissier E; Boulenger M; Maingon P; Corbion O; Schraub S. .I 200623 .U 90002785 .S Cancer 9001; 64(9):1853-8 .M Adenocarcinoma/IM; Adult; Aged; Antigen-Antibody Complex/AN; B-Lymphocytes/DE/IM; Carcinoma, Oat Cell/IM; Carcinoma, Squamous Cell/IM; Comparative Study; Human; IgA/AN; IgG/AN; IgM/AN; Immunocompetence/*; Lung Neoplasms/*IM/PA; Lymphocyte Transformation; Middle Age; Mitogens/PD; Neoplasm Metastasis/IM; Support, Non-U.S. Gov't; T-Lymphocytes/DE/IM. .T Immunocompetence in lung cancer. Relationship to extent of tumor burden and histologic type. .P JOURNAL ARTICLE. .W In vitro assays of immunocompetence were done in 60 patients with differing extents of tumor load and various histologic types of lung cancer and were compared to values obtained for 60 normal controls. Profound alterations in monoclonal antibody-defined T-lymphocytes and circulating B-cells were seen. All patients showed impaired blastogenic response to the mitogens used with the exception of a normal response to pokeweed mitogen (PWM) in patients with localized disease. Increase levels of serum IgG were seen in patients with localized disease whereas high levels of IgA was seen in patients with more advanced disease. Distant metastases were associated with low IgM levels. All patients studied regardless of stage and histologic type had elevated levels of circulating immunocomplexes. These findings indicate gross immunologic abnormalities in these patients. .A Pillai MR; Balaram P; Padmanabhan TK; Abraham T; Hareendran NK; Nair MK. .I 200624 .U 90002789 .S Cancer 9001; 64(9):1879-87 .M Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Combined/TU; Bone Marrow/*PA; Female; Follow-Up Studies; Human; Lymphoma/DT/*PA/RT; Male; Middle Age; Prognosis; Remission Induction. .T Diffuse large cell lymphoma with discordant bone marrow histology. Clinical features and biological implications [published erratum appears in Cancer 1990 Jan 1;65(1):64] .P JOURNAL ARTICLE. .W In patients with diffuse large cell lymphoma (LCL), bone marrow involvement at the time of diagnosis is a poor prognostic sign. Since 1980, the authors have encountered 13 patients LCL who had simultaneous bone marrow involvement by small cleaved cell lymphoma (11 cases) or mixed small and LCL (two cases), a phenomenon known as "discordant" or "divergent" bone marrow histology. The patients ranged in age from 33 to 85 years (median, 61 years) and presented most commonly with Stage III or IV disease, independent of bone marrow involvement. Seventy-seven percent achieved complete remission (CR) with combination chemotherapy; 50% of these eventually relapsed and died of their disease. One patient died of unrelated causes. No recurrences of low-grade lymphoma were observed, as judged either by clinical behavior or rebiopsy. The survival of the patients with discordant bone marrow histology was compared with that of patients with LCL with or without bone marrow involvement by LCL. Of the 11 patients with discordant marrow histology followed for a minimum of 2 years, four (36%) are long-term survivors; this is comparable to the 2-year survival of patients with LCL without bone marrow involvement (45%). In contrast, 89% of patients with bone marrow biopsy specimens positive for LCL died within 18 months from the time of diagnosis (mean survival, 5.7 months). All diffuse LCL tested were of B-lineage. The authors attempted to determine whether the presence of discordant bone marrow histologic types indicated an underlying low-grade B-cell lymphoma in these patients by evaluating the peripheral blood of the long-term survivors for the presence of clonal excess. Of the three surviving evaluable patients tested, one had evidence of clonal excess in the peripheral blood. For patients with LCL who have a simultaneous bone marrow biopsy positive for low-grade lymphoma (discordant marrow histology), survival is no different from that of patients with negative marrows, and markedly better than that for patients with marrows positive for diffuse LCL. The biological significance of discordant bone marrow histology is not clear at this time. .A Fisher DE; Jacobson JO; Ault KA; Harris NL. .I 200625 .U 90002791 .S Cancer 9001; 64(9):1894-900 .M Breast Neoplasms/MO/*PA/UL; Cell Cycle; Female; Flow Cytometry/*; Human; Lymph Nodes/PA; Middle Age; Multivariate Analysis; Ploidies; Prognosis; Proportional Hazards Models; Prospective Studies; Support, U.S. Gov't, P.H.S.; Survival Analysis. .T The relation of flow cytometry to clinical and biologic characteristics in women with node negative primary breast cancer. .P JOURNAL ARTICLE. .W Flow cytometry (FC) analysis including DNA index (ploidy status) and cell kinetics (%S and %S + G2/M) was done on frozen tissue of the primary lesions of 101 women with node negative (N-) breast cancer who were studied prospectively. Currently, 19% (19/101) of the patients have recurred. No significant relations have been found between recurrence or survival and age, estrogen/progesterone receptor status, tumor size, and tumor type. The DNA index (ploidy) was not related to any clinical variable, time to recurrence, or survival. Aneuploid tumors did, however, have significantly higher %S phase activity. Patients with %S activity less than or equal to the median value were significantly different from those patients with %S above the median. They were older and had a higher frequency of ER/PR positive and well- or moderately differentiated tumors. Patients with %S + G2/M greater than the median value showed shorter time to recurrence (P = .055) and shorter survival (P = .006), whereas %S alone was significantly associated only with survival. Multivariate analysis showed that neither DNA index nor cell kinetics was significantly associated with time to relapse. DNA index was not significantly associated with survival; %S was of borderline significance whereas %S + %G2/M was a significant independent predictor of survival. Although FC data may provide independent information related to survival in N-women, additional research in a larger number of patients is needed to define its precise role in patient management. .A Muss HB; Kute TE; Case LD; Smith LR; Booher C; Long R; Kammire L; Gregory B; Brockschmidt JK. .I 200626 .U 90002792 .S Cancer 9001; 64(9):1901-8 .M Aged; Aminoglutethimide/AD; Antineoplastic Agents, Combined/*TU; Breast Neoplasms/*DT/ME/MO; Diethylstilbestrol/AD; Female; Fluoxymesterone/AD; Human; Immunohistochemistry; Menopause; Middle Age; Neoplasm Recurrence, Local/MO; Paraffin; Receptors, Estrogen/*AN; Survival Analysis; Tamoxifen/AD/*TU. .T Immunohistochemical estrogen receptor determination in paraffin-embedded tissue. Prediction of response to hormonal treatment in advanced breast cancer. .P JOURNAL ARTICLE. .W A new immunohistochemical assay using a monoclonal estrogen receptor (ER) antibody (H222, Abbott Laboratories, North Chicago) for determination of ER in formalin-fixed paraffin-embedded tissue was applied to evaluate its clinical value in a group of 145 previously untreated patients with advanced breast cancer. Suitable histologic material was accessible in 137 of these patients, of whom 70% had ER-positive tumors. The ER-positive patients had a significantly longer median overall survival than ER-negative patients (67 versus 32 months, P much less than 0.001) and this was an effect of both a prolonged disease-free interval (27 versus 17 months, P less than 0.05) and a prolonged survival after recurrence (41 versus 15 months, P much less than 0.001). Response to endocrine therapy was obtained in 49% of the patients with ER-positive tumors and in 7% with ER-negative tumors (P much less than 0.001). Relationship between response and semiquantified individual staining features could not be established. It is concluded that ER analysis in formalin-fixed paraffin-embedded tissue offers clinically useful information for allocation of patients to endocrine therapy. .A Andersen J; Poulsen HS. .I 200627 .U 90002794 .S Cancer 9001; 64(9):1914-21 .M Adult; Aged; Aged, 80 and over; Breast Neoplasms/*PA/UL; Carcinoma, Ductal/*PA/UL; Cell Differentiation; Cell Nucleus/*UL; Female; Follow-Up Studies; Human; Lymphatic Metastasis; Middle Age; Mitotic Index; Multivariate Analysis; Neoplasm Invasiveness; Prognosis; Risk Factors. .T Prognostic value of histologic grade nuclear components of Scarff-Bloom-Richardson (SBR). An improved score modification based on a multivariate analysis of 1262 invasive ductal breast carcinomas. .P JOURNAL ARTICLE. .W We did a multivariate analysis of 1262 patients with operable, invasive ductal breast carcinoma to assess the prognostic value of the Scarff-Bloom-Richardson (SBR) histologic grading system. Nodal metastasis and SBR were the two most important factors for metastasis-free survival (MFS), P = 10-9 and P = 10-5, respectively, for total study time. In patients who were node negative, the SBR and International Union Against Cancer (UICC) stages were the most important for MFS (P = 4 X 10-4 and P = 0.03). In order to try to improve the SBR prognostic value, we first studied the three components of the SBR separately: ductoglandular differentiation proved the least predictive and nuclear pleomorphism and mitotic index the most predictive. A rearrangement of the two nuclear scores alone produced higher risk values and better risk separation of patient subpopulations than SBR, and eliminated the SBR from the multivariate model. This rearrangement, modified SBR (MSBR), defined five new risk subgroups with statistically different risk ratios for MFS (P = 3 X 10-8). SBR grade II (55% of patients) was separated into three MSBR groups significantly different according to MFS (P = 0.008). In the patients who were node negative, MSBR replaced the SBR and was the most important factor for prediction of relapse of MFS (P less than 0.00001). The MSBR is more accurate and predictive than the standard SBR grade and is particularly useful when the nodal status of the patient is negative or unknown. .A Le Doussal V; Tubiana-Hulin M; Friedman S; Hacene K; Spyratos F; Brunet M. .I 200628 .U 90002795 .S Cancer 9001; 64(9):1922-7 .M Adult; Aged; Breast Neoplasms/*ME; Carcinoma/*ME; Cytoplasm/ME; Female; Human; Menopause; Middle Age; Mitotic Index; Prognosis; Receptors, Estrogen/*AN; Receptors, Progesterone/*AN; Retrospective Studies; Support, Non-U.S. Gov't. .T Cell kinetics and hormonal receptor status in inflammatory breast carcinoma. Comparison with locally advanced disease. .P JOURNAL ARTICLE. .W The biological and prognostic role of hormone receptor status and proliferative activity have been studied in two series of patients affected by inflammatory breast carcinoma (IBC, 28 patients) and locally advanced breast cancer (LABC, 50 patients). Estrogen receptor (ER) and progesterone receptor (PgR) were measured by dextran-coated charcoal (DCC) method whereas proliferative activity was measured by 3H-thymidine autoradiographic labeling index (LI). The percentages of ER+ and PgR+ cases resulted lower in IBC than in LABC (ER+, 44% versus 64%; PgR+, 30% versus 51%, respectively), pertaining to both premenopausal and postmenopausal women. Inflammatory breast carcinoma showed a higher median LI value than LABC (3.5% versus 1.6%; P = 0.006). Regarding clinical aspects, time to progression (TTP) in IBC patients was not affected by hormone receptor status (19 evaluable patients) or by LI (17 evaluable patients); PgR+ status and low LI resulted important for individualizing women with a longer median overall survival (OS). Inflammatory breast carcinoma has been verified to be a heterogeneous biological entity for which hormone receptors and cell kinetics could be useful in identifying patients with different prognoses and therefore candidates for a personalized therapy. .A Paradiso A; Tommasi S; Brandi M; Marzullo F; Simone G; Lorusso V; Mangia A; De Lena M. .I 200629 .U 90002796 .S Cancer 9001; 64(9):1928-36 .M Adult; Case Report; Combined Modality Therapy; Female; Hemangiopericytoma/*DI/PA/SU; Human; Lung Neoplasms/*DI/PA/SU; Magnetic Resonance Imaging; Neoplasm Invasiveness/DI; Thoracotomy; Tomography, X-Ray Computed. .T Massive pulmonary hemangiopericytoma. An innovative approach to evaluation and treatment. .P JOURNAL ARTICLE. .W The authors report the case of a 39-year-old woman with a massive malignant pulmonary hemangiopericytoma. The clinical presentation and histologic findings were typical of this rare entity, but workup and treatment were challenging because of the size and location of the tumor. Magnetic resonance imaging (MRI) proved to be critical in the preoperative evaluation because of its unique ability to delineate the precise anatomical extent of this highly vascular neoplasm. Previous treatment of this patient with exploratory thoracotomy and chemotherapy had been unsuccessful. The authors used an innovative approach to treatment which included complete surgical resection via combined median sternotomy and thoracotomy, along with intraoperative and postoperative radiotherapy. The patient is disease-free 28 months after surgery. .A Rusch VW; Shuman WP; Schmidt R; Laramore GE. .I 200630 .U 90002798 .S Cancer 9001; 64(9):1948-51 .M Aged; Carcinoma, Oat Cell/*PA/TH/UL; Case Report; Combined Modality Therapy; Female; Human; Neuroepithelioma/PA/TH/UL; Vaginal Neoplasms/*PA/TH/UL. .T Neuroepithelial small cell carcinoma of the vagina. .P JOURNAL ARTICLE. .W We studied two patients with primary vaginal small cell carcinomas. Their tumors show histologic and ultrastructural neuroepithelial elements similar to those reported in the literature in the cervix and the lung. The clinical behavior of the tumors was aggressive in both patients. Ultrastructural study of small cell genital tract neoplasms is indicated to help classify this disease. Adjunctive therapy may be required for neoplasms of neuroepithelial origin. .A Chafe W. .I 200631 .U 90002799 .S Cancer 9001; 64(9):1952-60 .M Adolescence; Antineoplastic Agents, Combined/TU; Child; Child, Preschool; Combined Modality Therapy; Female; Human; Male; Neoplasm Metastasis; Neoplasms, Embryonal and Mixed/*DI/TH; Neuroepithelioma/*DI/TH; Pediatrics; Peripheral Nerve Neoplasms/*DI/TH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Peripheral primitive neuroectodermal tumor (peripheral neuroepithelioma) in children. A review of the St. Jude experience and controversies in diagnosis and management. .P JOURNAL ARTICLE. .W All patients diagnosed with primitive neuroectodermal tumor (PNET) and extraosseous Ewing's sarcoma in one institution between 1962 and 1987 were reviewed. Of the 26 cases studied, 16 had been diagnosed originally as PNETs, seven tumors were rediagnosed as PNET or EOE by histologic review, and three tumors had an original diagnosis of extraosseous Ewing's sarcoma. To determine whether these diagnoses determine a group of tumors with unique biologic behavior and identifiable pathologic characteristics, clinical and treatment response data were compiled, and electron microscopic and immunohistochemical studies were done for those patients with adequate samples. With combined modality therapy, this group achieved a substantially shorter disease control interval than patients with disseminated osseous Ewing's sarcoma or disseminated neuroblastoma--10.8 months versus 17 months and 16 months, respectively. The pattern of relapse and distant spread also differed among these tumor types. Immunohistochemical studies (for example, neuron-specific enolase and beta 2 microglobulin) were helpful in confirming the diagnosis but were not definitive in themselves. Tentative diagnostic criteria are proposed for use in studies designed to provide further information on the nature and treatment of PNET. Some of the controversies regarding diagnosis are discussed. The authors propose a uniform approach to treatment of extraosseous Ewing's sarcoma and PNET in order to try to clarify their relation. .A Marina NM; Etcubanas E; Parham DM; Bowman LC; Green A. .I 200632 .U 90002800 .S Cancer 9001; 64(9):1961-4 .M Aged; Case Report; Epidural Neoplasms/*CO/SC; Female; Human; Leukemia, Lymphocytic, Chronic/*CO; Spinal Cord Compression/*CO/MO; Tomography, X-Ray Computed. .T Spinal epidural compression in chronic lymphocytic leukemia. .P JOURNAL ARTICLE. .W Spinal epidural compression is a rare neurologic complication in patients with lymphoma. It occurs mostly in those with intermediate-grade to high-grade malignancy disease. This type of neurologic involvement has not been described in chronic lymphocytic leukemia (CLL). A patient with a long, stable CLL course developed spinal epidural compression and consequently died. The frequency of spinal epidural compression in lymphoma, according to the histologic subtypes and the considerations in making the right choice of therapy are discussed in light of the presented case. .A Michalevicz R; Burstein A; Razon N; Reider I; Ilie B. .I 200633 .U 90002801 .S Cancer 9001; 64(9):1965-7 .M Aged; Bone and Bones/ME; Breast Neoplasms/*CO/ME/PC; Calcitriol/BL; Calcium/BL; Case Report; Female; Human; Hyperparathyroidism/*CO/ME; Menopause/*; Parathyroid Hormones/BL; Tamoxifen/*TU. .T Amelioration of postmenopausal primary hyperparathyroidism during adjuvant tamoxifen for breast cancer. .P JOURNAL ARTICLE. .W The effects of adjuvant treatment with tamoxifen on bone metabolism in a postmenopausal woman with primary hyperparathyroidism is presented. A 69-year-old woman with increased serum ionized calcium, parathyroid hormone, and 1,25-(OH)2 vitamin D levels and a normal bone scan received tamoxifen 10 mg three times daily for 1 year. During treatment bone turnover decreased whereas parathyroid hormone increased further. After cessation of treatment the calcium metabolic variables returned to pretreatment levels. The antiestrogen tamoxifen seems to behave as an estrogen on bone metabolism in primary hyperparathyroidism. .A Kristensen B; Mouridsen HT; Holmegaard SN; Transbol I. .I 200634 .U 90002802 .S Cancer 9001; 64(9):1968-70 .M Adult; Aged; Ampicillin/TU; Female; Human; Immunosuppressive Agents/*AE; Listeria Infections/*CO/DT/MO; Male; Meningitis, Listeria/CO; Middle Age; Neoplasms/*CO/DT; Trimethoprim-Sulfamethoxazole Combination/TU; Vancomycin/TU. .T Spectrum and outcome of microbiologically documented listeria monocytogenes infections in cancer patients. .P JOURNAL ARTICLE. .W At the M.D. Anderson Cancer Center (Houston), Listeria monocytogenes was cultured from 14 patients between 1980 and 1987. The case records of 11 of these patients were reviewed. Underlying malignancies included acute leukemia (three), lymphoma (two), myeloma (one), adenocarcinoma of colon (two), carcinoma of breast (one), carcinoma of lung (one), and Kaposi's sarcoma associated with the acquired immune deficiency syndrome (one). Listeria monocytogenes was cultured from blood (eight patients), cerebrospinal fluid (CSF) (two patients), and from both blood and CSF in one patient. All patients were receiving immunosuppressive therapy including corticosteroids in seven. An absolute neutrophil count of less than 1000/mm3 was noted in five. Bacteremia was the predominant type of infection and ten patients responded to antimicrobial therapy. .A Khardori N; Berkey P; Hayat S; Rosenbaum B; Bodey GP. .I 200635 .U 90002803 .S Cancer 9001; 64(9):1971-5 .M Adult; Age Factors; Aged; Aged, 80 and over; Colonic Neoplasms/*GE/PA; Disease Susceptibility; Human; Information Systems/*; Middle Age; Pedigree; Rectal Neoplasms/*GE/PA; Registries; Support, U.S. Gov't, P.H.S.; Utah. .T Characteristics of familial colon cancer in a large population data base. .P JOURNAL ARTICLE. .W Early age onset and proximal colonic location are two specific characteristics of colon cancer which have been used clinically to assess the risk that an individual case is of familial rather than sporadic origin. This practice derives from the observation that these characteristics are typical of the rare, nonpolyposis inherited colorectal cancer syndromes. This study examines these two characteristics in cases of common colon cancer to determine whether they actually distinguish individuals at increased risk for familial colorectal cancer. Familial clusters of colon cancer in the Utah Population Data Base were examined. Common colon cancers were found to cluster excessively in families; however, the measure of familial clustering for distal colonic cases was increased to the same degree as proximal colonic cases. Early age onset was likewise not a distinguishing factor of familial cases. These results suggest that factors other than those that predispose to the rare syndromes are important in determining familial risk for common colon cancers, and that the absence of these two clinical features should not suggest the absence of familial risk of colorectal cancer. .A Cannon-Albright LA; Thomas TC; Bishop DT; Skolnick MH; Burt RW. .I 200636 .U 90003204 .S Cathet Cardiovasc Diagn 9001; 18(2):102-7 .M Case Report; Coronary Disease/*CO/PP; Female; Human; Middle Age; Mitral Valve Insufficiency/CO/*PP; Papillary Muscles/*PP. .T Spontaneous cyclic severe mitral regurgitation. .P JOURNAL ARTICLE. .W Two patients are described with spontaneous wide fluctuations in the size of pulmonary capillary wedge pressure V waves thought to be related to cyclic spontaneous variations in the degree of mitral regurgitation over very short periods of time. The findings are thought to represent a hemodynamically distinct syndrome intermediate between chronic severe and acute severe mitral regurgitation. .A Engel PJ; Wayne D. .I 200637 .U 90003206 .S Cathet Cardiovasc Diagn 9001; 18(2):118-20 .M Aged; Angioplasty, Transluminal/*MT; Brachial Artery; Human; Male; Middle Age. .T Percutaneous brachial approach for transluminal coronary angioplasty. .P JOURNAL ARTICLE. .W Transluminal coronary angioplasty from the arm is performed generally with cutdown and brachial arteriotomy. We describe a brachial percutaneous technique for coronary angioplasty, almost similar to the femoral one, with a special focus on the prevention of induced vasoconstriction. Our preliminary results are satisfactory and without complications: 13 procedures in 11 patients have been performed over a 30 month period, with the sheaths left in place for 4-6 h after the procedure. This method could be an easy alternative to the Sones technique for operators who are essentially familiar with the femoral percutaneous arterial approach. .A Maouad J; Hebert JL; Guermonprez JL. .I 200638 .U 90003207 .S Cathet Cardiovasc Diagn 9001; 18(2):121-4 .M Aged; Angioplasty, Transluminal/AE/*IS/MT; Brachial Artery; Female; Human; Male; Middle Age. .T Percutaneous brachial coronary angioplasty utilizing a standard side arm sheath introducer system. .P JOURNAL ARTICLE. .W A percutaneous approach via the brachial artery for coronary angioplasty is described. The technique employs a standard side arm sheath introducer system routinely intended for the femoral artery. Initial experience in ten cases shows this to be a relatively easy and safe alternative to conventional brachial arteriotomy, with some distinct advantages. It is less time consuming, permits the use of a variety of standard preformed guiding catheters, is associated with less patient discomfort, and the sheaths may be left in place for many hours if the angioplasty is complicated and/or long-term anticoagulation is desirable. Complications were limited to the female patients in this series. This technique is most suited to those operators who employ the brachial approach infrequently and only out of necessity in patients with severe peripheral vascular disease. .A Korr KS; Januski V. .I 200639 .U 90003208 .S Cathet Cardiovasc Diagn 9001; 18(2):128-9 .M Aortic Valve/*PH/PP; Aortic Valve Stenosis/DI/PP; Femoral Artery/*PH/PP; Heart Function Tests/*MT; Heart Ventricle/PH/PP; Human. .T Accurate determination of the transaortic valve gradient using simultaneous left ventricular and femoral artery pressures [letter] .P LETTER. .A Chao JC; Hwang MH. .I 200640 .U 90003209 .S Cathet Cardiovasc Diagn 9001; 18(2):129 .M Heart Valve Prosthesis/*AE; Human; Ventricular Outflow Obstruction/*ET. .T Left ventricular outflow tract obstruction [letter] .P LETTER. .A Freedberg RS; Kronzon I. .I 200641 .U 90003210 .S Cathet Cardiovasc Diagn 9001; 18(2):129-30 .M Biopsy, Needle/*MT; Human; Pericardium/*PA. .T Aspiring to aspirate--the pericardiocentesis correspondence. .P JOURNAL ARTICLE. .A Bloomfield DA. .I 200642 .U 90003212 .S Cathet Cardiovasc Diagn 9001; 18(2):67-72 .M Adult; Angina Pectoris/DT/ET/*TH; Angioplasty, Transluminal/*; Case Report; Coronary Disease/*TH; Coronary Thrombosis/CO/DT/*TH; Fibrinolytic Agents/*TU; Human; Male; Middle Age. .T Staged thrombolysis and percutaneous transluminal coronary angioplasty for unstable and postinfarction angina. .P JOURNAL ARTICLE. .W The precise timing of intravenous thrombolysis and coronary angioplasty continues to be evaluated for patients who have coronary thrombosis and unstable angina or postinfarction angina. Coronary angioplasty is effective for these patients but is associated with thromboembolic coronary occlusion in 24% to 29% of cases. After adjunctive intravenous thrombolysis and oral antiplatelet therapy to improve the success rate and to decrease the risk of acute occlusion, deferred angioplasty was successful in three patients with intracoronary thrombus and unstable angina or postinfarction angina. Staged thrombolysis and deferred angioplasty is feasible for selected patients with these acute coronary syndromes. .A Hurley DV; Bresnahan DR; Holmes DR Jr. .I 200643 .U 90003213 .S Cathet Cardiovasc Diagn 9001; 18(2):73-8 .M Aortic Valve Stenosis/*TH; Balloon Dilatation/*; Cerebral Ventricles/*PH; Human. .T Effect of balloon aortic valvuloplasty on the dynamics of left ventricular ejection. .P JOURNAL ARTICLE. .W To evaluate the effect of balloon aortic valvuloplasty on left ventricular ejection dynamics, simultaneous left ventricular and aortic pressures were obtained by use of a micromanometer catheter in nine patients before and after the procedure. Ejection times, stroke volumes (thermodilution), ejection rates, and pressure gradients were measured. For each parameter, ejection was then divided into two components: accelerative (onset systole to peak gradient) and decelerative (peak gradient to end systole). After valvuloplasty, there was 1) a decrease in overall ejection time and in mean and peak pressure gradients; 2) an increase in overall ejection rate; 3) no change in stroke volume or heart rate; 4) an increase in both accelerative and decelerative ejection rates and a decrease in the decelerative ejection time (expressed as a percentage of the R-R interval); and 5) a decrease in the time for the ejection of the final 25% of stroke volume (P less than 0.01) and time occupied by the final 25% of the gradient. Immediately following balloon aortic valvuloplasty, there is a decrease in ejection time and in increase in ejection rate. Balloon aortic valvuloplasty has a significant effect on the dynamics of left ventricle ejection, with changes primarily expressed in late systole. By improving the mobility of calcified leaflets, balloon aortic valvuloplasty may reduce the forces opposing forward blood movement during the decelerative phase of ejection. .A Ferguson JJ 3d; Bush HS; Riuli EP. .I 200644 .U 90003214 .S Cathet Cardiovasc Diagn 9001; 18(2):79-84 .M Coronary Disease/*MO/PP; Heart Ventricle/*PP; Human; Support, Non-U.S. Gov't. .T Weighted ventriculographic wall motion score for improved survival prediction in patients with coronary artery disease. Coronary Artery Surgery Study. .P JOURNAL ARTICLE. .W Global ventricular function parameters such as the ejection fraction and the sum of wall motion scores for segments of the left ventricle are excellent predictors of long-term survival in patients with coronary heart disease. These are usually determined from a monoplane right anterior oblique view. It was hypothesized that a biplane weighted wall motion score that included the left anterior oblique projection might better predict survival. A new score (BISCORE) was derived for 1,433 Mayo Clinic ventriculograms coded by the methods of the Coronary Artery Surgery Study (CASS). Weighting coefficients for each left ventricular segment were derived by the proportional hazards technique, and this resulted in the equation BISCORE = 120 - (8.6 x anterobasal + 3.4 x basal septum + 2.9 x apical + 2.7 x posterolateral + 2.4 diaphragmatic), which yielded a score from 0 (all segments aneurysmal) to 100 (all segments normal). This score stratified the original 1,433 patients into distinct groups by survival. As a single variable it was better than previous wall motion scores and ejection fraction at predicting survival. When prospectively applied to 5,172 Coronary Artery Surgery Study patients, this new score again proved to be a better predictor of survival than previous unweighted scores. Since the new score contains terms from the left anterior oblique ventriculographic projection, it is concluded that this projection adds information to that of the right anterior oblique projection regarding survival. Furthermore, this weighted score appears more highly associated with survival than unweighted scores. .A Schwartz RS; Ilstrup DM; Vlietstra RE; Bove AA; Smith HC. .I 200645 .U 90003215 .S Cathet Cardiovasc Diagn 9001; 18(2):85-9 .M Adult; Aged; Female; Heart Atrium/*PP; Heart Function Tests/*; Heart Ventricle/*PP; Human; Male; Middle Age; Myocardial Infarction/*PP. .T Left atrial conduit function for left ventricular filling dynamics in patient with myocardial infarction. .P JOURNAL ARTICLE. .W This study observed the left function in determining filling dynamics of the left ventricle in patients with myocardial infarction. The study consisted of eight control subjects and ten patients with myocardial infarction. The left ventricular filling volume is considered to be composed of the left atrial passive emptying, active emptying, and conduit volumes. The change of left ventricular filling volume was correlated with that of conduit volume (r = .87, P less than .01). However, the change of left ventricular filling volume did not have any correlation to those of left atrial passive emptying and active emptying volumes. These results suggested that the left atrial conduit function was important in determining filling dynamics of the left ventricle. .A Toma Y; Matsuda Y; Moritani K; Ryoke T; Katayama K; Miura T; Ogawa H; Matsuda M; Matsuzaki M; Kusukawa R. .I 200646 .U 90003216 .S Cathet Cardiovasc Diagn 9001; 18(2):90-5 .M Aged; Angioplasty, Transluminal/*; Case Report; Female; Heart Valve Diseases/PA/*TH; Human; Middle Age. .T Valve injury and repair in balloon aortic valvuloplasty. .P JOURNAL ARTICLE. .W Aortic valves 0.5, and 4.5 months after successful percutaneous balloon aortic valvuloplasty (BAV) were examined. BAV caused macroscopic and microscopic fractures in calcific deposits. An inflammatory response was identified that may lead to valvular scarring. This process may be an important factor in the development of restenosis after BAV. .A Farb A; Moses JW; Wallerson DC; Gold JP; Subramanian VA. .I 200647 .U 90003217 .S Cathet Cardiovasc Diagn 9001; 18(2):96-8 .M Aged; Aged, 80 and over; Angioplasty, Transluminal/*; Aortic Valve Stenosis/*TH; Human; Middle Age; Recurrence. .T Repeat balloon aortic valvuloplasty for aortic valve restenosis. .P JOURNAL ARTICLE. .W Effective balloon aortic valvuloplasty (BAV) is limited restenosis. After aortic valve restenosis six patients underwent repeat BAV. In spite of the use of larger balloons there was a trend toward a less satisfactory result after repeat BAV (0.98 +/- .26 cm2 vs. 1.2 +/- .26 cm2), which did not reach statistical significance, P = .14. Mortality of the patients at 6 months was 50%. Repeat BAV may be less efficacious than the original procedure. .A Ross TC; Banks AK; Collins TJ; Ramee SR; White CJ; Moore JW. .I 200648 .U 90003218 .S Cathet Cardiovasc Diagn 9001; 18(2):99-101 .M Aged; Case Report; Female; Gastrointestinal Hemorrhage/*ET; Heart Catheterization/*AE; Human; Male; Middle Age. .T Gastrointestinal hemorrhage as a complication of cardiac catheterization. .P JOURNAL ARTICLE. .W This report describes three patients who developed the rate complication of gastrointestinal hemorrhage following cardiac catheterization. These cases illustrate the diverse mechanisms by which bleeding may occur. The important predisposing factors appear to be widespread atherosclerosis, prolonged hypotension, and gastrointestinal disease potentially associated with bleeding. .A Mukerji V; Comens SM; Alpert MA. .I 200649 .U 90003533 .S Can J Anaesth 9001; 36(5):491-3 .M Administration, Intranasal; Anesthetics/AD; Fentanyl/AA/AD; Human; Narcotics/*AD; Preanesthetic Medication. .T Intranasal opiates: old route for new drugs [editorial] .P EDITORIAL. .A Ralley FE. .I 200650 .U 90003534 .S Can J Anaesth 9001; 36(5):494-7 .M Absorption; Administration, Intranasal; Adult; Anesthetics/*AD/BL/PK; Biological Availability; Comparative Study; Female; Fentanyl/*AA/AD/BL/PK; Human; Hypnotics and Sedatives; Injections, Intravenous; Male; Middle Age; Oxygen/BL; Preanesthetic Medication/*; Random Allocation; Respiration/DE; Time Factors. .T Comparison of intravenous and intranasal sufentanil absorption and sedation [see comments] .P JOURNAL ARTICLE. .W The absorption and sedation following an intranasal dose of sufentanil were evaluated and compared with those of the same dose given intravenously. Sixteen adult patients scheduled for elective surgery were randomly allocated to receive as premedication 15 micrograms sufentanil either intravenously or intranasally. Before administration and at fixed time intervals thereafter, the degree of sedation was assessed, vital signs were recorded and venous blood samples were taken for the determination of sufentanil plasma concentrations. Peroperative sedation of rapid onset and limited duration was seen in both groups. However, the onset of sedation was more rapid after intravenous injection. At 10 min, all patients in the IV group were sedated versus only two in the intranasal group (P less than 0.01). No significant intergroup differences in sedation were seen at 20 to 60 min. This clinical effect is in agreement with the measured plasma levels, which were significantly lower after intranasal application at 5 and 10 min, being 36 and 56 per cent of those after IV dosing, respectively. From 30 min, plasma concentrations were virtually identical for the two routes of administration. The AUC0-120 min after intranasal dosing was 78 per cent of that after intravenous injection. Intranasal dosing induced no clinically significant changes in vital signs, whereas after IV sufentanil, a clinically significant decrease in PaO2 was seen at 5 min. The results of this study show that sufentanil, when administered intranasally, is rapidly and effectively absorbed from the human nasal mucosa, so that this route may be an attractive alternative for a premedicant, avoiding the discomfort of an intravenous or intramuscular injection. .A Helmers JH; Noorduin H; Van Peer A; Van Leeuwen L; Zuurmond WW. .I 200651 .U 90003535 .S Can J Anaesth 9001; 36(5):498-502 .M Adult; Anesthesia, Conduction/*; Anesthesia, Intravenous/*; Arm/*; Blood Volume; Double-Blind Method; Female; Forearm/BS; Hand/IR; Human; Lidocaine/AD/*TO; Male; Muscles/DE/PH; Random Allocation; Tourniquets/*; Veins. .T Decreasing the toxic potential of intravenous regional anaesthesia. .P JOURNAL ARTICLE. .W In an attempt to reduce the dose of local anaesthetic agent during intravenous regional anaesthesia (IVRA) of the upper limb, we have used a forearm tourniquet in 12 adult volunteers. The volume of the forearm venous system was predetermined angiographically. We performed IVRA with three solutions of lidocaine (0.25, 0.375, 0.5 per cent) administered in a volume equal to the forearm venous system. Angiographic results indicate that: a forearm tourniquet provides adequate vascular isolation; the volume of the forearm venous system can be correlated with body weight; the progression of the fluid in the venous system follows a pattern that is similar for all patients with the small veins of the distal forearm and proximal hand being filled last. With this technique, lidocaine 0.5 per cent resulted in a dose of 1.5 mg.kg-1 and provided excellent analgesia. Lower concentrations were unsatisfactory. We conclude that the use of a forearm tourniquet allows reduction of the local anaesthetic dose to a non-toxic level and thus increases the safety of IVRA. .A Plourde G; Barry PP; Tardif L; Lepage Y; Hardy JF. .I 200652 .U 90003538 .S Can J Anaesth 9001; 36(5):515-8 .M Adult; Anesthesia, Epidural/*; Anesthetics, Local/*AD; Bicarbonates; Double-Blind Method; Female; Human; Hydrogen-Ion Concentration; Leg/SU; Procaine/*AA/AD; Random Allocation; Sodium; Sodium Chloride; Support, Non-U.S. Gov't; Time Factors. .T pH-adjustment of 2-chloroprocaine quickens the onset of epidural anaesthesia. .P JOURNAL ARTICLE. .W The effect of pH-adjustment of three per cent 2-chloroprocaine (2-CP, Nesacaine MPF) on the onset, duration, and spread of epidural analgesia and anaesthesia was studied in patients undergoing lower extremity surgery. Forty ASA physical status I and II patients were randomized to two groups. In a double-blinded fashion, patients in both groups received an epidural injection of 15 ml of local anaesthetic (LA) solution via a Tuohy needle at the L3-4 interspace. Local anaesthesia for Group I was prepared by adding 3 mEq NaHCO3 to 27 ml three per cent 2-CP and for Group II was prepared by adding 3 ml 0.9 per cent NaCl to 27 ml three per cent 2-CP. Both solutions contained epinephrine (1:200,000). The pH of commercially prepared Nesacaine MPF was 3.19 +/- 0.02. The pH of the solutions used for Group I and Group II patients were 7.32 +/- 0.01 and 3.27 +/- 0.02, respectively. Times to analgesia and anaesthesia at the L2 dermatome were significantly decreased in Group I patients by 2.5 and 6.6 minutes, respectively. Likewise, pH-adjustment accelerated the attainment of maximum level of block by 2.8 min. No statistical differences were found between groups in the maximum level of epidural block, or in time to 2-segment regression. No precipitation of LA was observed in pH-adjusted solutions of 2-CP after 24 hours. We recommend the use of pH-adjusted three per cent 2-CP (Nesacaine MPF) to accelerate the onset of epidural block. .A Stevens RA; Chester WL; Schubert A; Brandon D; Grueter JA; Zumrick J. .I 200653 .U 90003540 .S Can J Anaesth 9001; 36(5):523-5 .M Adult; Anesthesia, Inhalation/*; Anesthesia, Obstetrical/*; Female; Functional Residual Capacity; Human; Nitrogen/AN/*PK; Oxygen/AD; Pregnancy/*ME; Respiration; Time Factors. .T Denitrogenation in pregnancy. .P JOURNAL ARTICLE. .W This study measured nitrogen washout in ten pregnant and nine non-pregnant women to understand better how pregnancy effects denitrogenation. Nitrogen concentration was monitored continuously while the women breathed 100 per cent O2 for three minutes and took four deep breaths of 100 per cent O2 using a circle anaesthesia system and 8 L.min-1 fresh gas flow. Parturients achieved 95 per cent denitrogenation significantly (P less than 0.0005) faster than non-pregnant women (54.5 +/- 17.8 vs 110.8 +/- 35.7 sec). In parturients, denitrogenation for three minutes lowered expired N2 concentration to 1.0 +/- 0.2 per cent while four deep breaths lowered it to 5.1 +/- 1.7 per cent (P less than 0.0001). This difference, while statistically significant, is predicted to supply only 10-15 sec of extra protection against hypoxaemia, and thus is probably not clinically significant. The authors conclude that either two minutes of tidal breathing or four deep breaths of 100 per cent O2 provide adequate denitrogenation and similar protection against apnoeic hypoxaemia in normal parturients. .A Norris MC; Kirkland MR; Torjman MC; Goldberg ME. .I 200654 .U 90003541 .S Can J Anaesth 9001; 36(5):526-9 .M Anesthesia, Rectal/*; Blood Flow Velocity/DE; Blood Pressure/DE; Cardiac Output/DE; Child, Preschool; Echocardiography; Echocardiography, Doppler; Heart Rate/DE; Hemodynamics/*DE; Human; Infant; Methohexital/AD/*PD; Pulmonary Artery/PH; Stroke Volume/DE. .T Haemodynamic effects of rectal methohexitone for induction of anaesthesia in children. .P JOURNAL ARTICLE. .W Pulsed Doppler and two-dimensional echocardiography were used to determine the haemodynamic effects of rectal methohexitone in 12 children 32.4 +/- 3.8 months old and weighing 13.3 +/- 1.1 kg (mean +/- SEM). Heart rate, blood pressure and echocardiographic measurements of cardiac output, stroke volume and left ventricular end-diastolic and end-systolic volumes were obtained prior to the induction of anaesthesia. Anaesthesia was induced with 25 mg.kg-1 two per cent rectal methohexitone. Immediately following the onset of sleep all cardiovascular measurements were repeated. Following the induction of anaesthesia with rectal methohexitone there was a significant increase in heart rate. Blood pressure, cardiac index, stroke volume and ejection fraction were unchanged. It is concluded that rectal administration of two per cent methohexitone for the induction of anaesthesia in healthy paediatric patients has minimal haemodynamic effect. .A Forbes RB; Murray DJ; Dull DL; Mahoney LT. .I 200655 .U 90003542 .S Can J Anaesth 9001; 36(5):530-2 .M Air Pollutants/AN; Anesthesia, Inhalation/*IS; Equipment Contamination/*PC; Halothane/*/AN; Human; Malignant Hyperthermia/*PC; Nebulizers and Vaporizers; Oxygen; Spectrophotometry, Infrared; Time Factors. .T Malignant hyperthermia and the clean machine. .P JOURNAL ARTICLE. .W Following use with halothane, ten anaesthestic machines were sampled using infrared analysis for halothane contamination. Baseline measurements of halothane were made in the room and at the machine's common gas outlet. Five per cent halothane with four litres per minute oxygen flow was delivered for ten minutes into a scavenged breathing circuit. Halothane was then discontinued, an oxygen flow rate of 12 litres per minute was begun, and continuous measurements were made until the halothane concentration became undetectable. Baseline measurements of the rooms and anaesthestic machines ranged from 0 to 0.8 parts per million. Following the oxygen flow, the halothane concentration decreased to undetectable levels within six minutes in all ten machines. .A McGraw TT; Keon TP. .I 200656 .U 90003544 .S Can J Anaesth 9001; 36(5):539-44 .M Adult; Aged; Anesthesia, General; Blood Pressure; Cardiac Output; Coronary Disease/*ET/*SU; Electrocardiography; Electrocardiography, Ambulatory; Heart Rate; Human; Intraoperative Care; Intraoperative Complications/*; Middle Age; Preoperative Care; Probability; Pulmonary Wedge Pressure; Venous Pressure. .T Failure to predict intraoperative myocardial ischaemia in patients with coronary artery disease. .P JOURNAL ARTICLE. .W Patients with severe coronary artery disease were studied to determine if the preoperative assessment or intraoperative haemodynamic monitoring could predict the occurrence of myocardial ischaemia. Thirty-eight patients undergoing coronary artery surgery who had normal electrocardiograms before induction of anaesthesia were included. Leads II and CS5 were recorded on a Holter monitor and radial arterial and pulmonary artery catheters were used to measure haemodynamic variables. Eight patients developed ST-segment changes greater than or equal to 0.1 mV before sternotomy. Preoperative factors could not be used to predict which patients would develop ST-segment changes. In all 38 patients haemodynamic determinants of myocardial oxygen supply and demand remained within an optimal range despite evidence of ischaemia in eight. This syndrome of ECG changes in the absence of tachycardia and hypertension resembles the syndrome of silent ischaemia documented in awake patients. Our findings suggest that myocardial ischaemia may be caused by decreases in coronary blood flow not associated with changes in haemodynamic variables. .A Smith H; Nathan H; Harrison M. .I 200657 .U 90003546 .S Can J Anaesth 9001; 36(5):554-9 .M Anesthesia, Inhalation; Animal; Animals, Newborn; Body Temperature; Bradycardia/*ET; Catheterization, Central Venous/*/IS; Cold; Electrocardiography/*; Halothane/AD; Heat; Sodium Chloride/AD; Support, Non-U.S. Gov't; Swine; Tidal Volume; Vagotomy; Vagus Nerve/PH. .T Factors influencing the R-R interval during central venous injection in newborn swine. .P JOURNAL ARTICLE. .W Seven Yorkshire swine, ages 7-11 days and weighing 1.4-2.8 kg were studied to determine the effects of temperature and volume of injectate, depth of anaesthesia, position of the central venous catheter tip and vagotomy on the R-R interval after central venous injection of saline. The swine were anaesthetized with halothane in 100 per cent oxygen and their lungs ventilated to normocapnia. The length of the R-R varied inversely with the temperature of the injectate between 0 and 20 degrees C reaching a maximum prolongation of 152 per cent above control values with 0 degrees C saline. Injecting saline at 37 degrees C did not affect the R-R interval. The length of the R-R interval varied directly with the volume of injectate between 1.5 and 4.5 ml.kg-1 (P less than 0.05). The R-R interval response also varied directly with the depth of anaesthesia: the post-injection R-R interval increased from 185 per cent to 341 per cent as the end-tidal halothane concentration increased from 0.45 to 1.20 per cent. The position of the tip of the central venous catheter that produced the maximum increase in the R-R interval, as determined radiographically, was at the junction of the superior vena cava and the right atrium. Neither bilateral vagotomy nor atropine (50 micrograms.kg-1) affected the R-R interval after injecting 3 ml.kg-1 saline 0 degrees C. We conclude that the increases in R-R interval after injection of fluid into the right atrium are due to direct effects on the nerve conduction system of the heart, possibly on the sino-atrial node. .A Oyston JP; Burrows FA; Lerman J. .I 200658 .U 90003548 .S Can J Anaesth 9001; 36(5):565-7 .M Adult; Anesthesia, Intravenous; Blood Pressure/DE; Comparative Study; Double-Blind Method; Female; Heart Rate/DE; Human; Injections, Intravenous; Intraoperative Care/*; Male; Nausea/*PC; Placebos; Postoperative Complications/*PC; Prochlorperazine/AD/*TU; Prospective Studies; Random Allocation; Vomiting/*PC. .T Intraoperative prochlorperazine for prevention of post-operative nausea and vomiting. .P JOURNAL ARTICLE. .W The effectiveness of 10 mg IV prochlorperazine in preventing postoperative nausea and vomiting was compared with placebo when given perioperatively to 100 patients in a prospective double-blind randomized trial. The occurrence of nausea and vomiting was assessed in the recovery room prior to and after narcotic administration for pain relief. No statistically significant difference in the frequency of postoperative nausea and vomiting was found between the treatment and control groups. .A Cramb R; Fargas-Babjak A; Hirano G. .I 200659 .U 90003552 .S Can J Anaesth 9001; 36(5):590-2 .M Adult; Anesthesia, Intravenous/AE; Apnea/ET; Autonomic Nervous System Diseases/*PP; Bradycardia/ET; Case Report; Diabetes Mellitus, Insulin-Dependent/*PP; Diabetic Neuropathies/*PP; Female; Heart Arrest/ET; Heart Diseases/*PP; Human; Kidney Transplantation/*/AE; Myocardial Diseases/ET. .T Renal transplantation and diabetic autonomic neuropathy. .P JOURNAL ARTICLE. .W This report describes six episodes of cardiovascular collapse in the perioperative period of a young diabetic woman undergoing general anaesthesia for renal transplantation and a similar episode after a second anaesthetic. She was subsequently found to have an autonomic neuropathy. Recommendations for the management of similar patients are made. .A Thomas AN; Pollard BJ. .I 200660 .U 90003553 .S Can J Anaesth 9001; 36(5):593-7 .M Adrenergic Beta Receptor Blockaders/AD/*TU; Aged; Anesthesia, Intravenous; Case Report; Coronary Disease/*DT; Diabetes Mellitus, Non-Insulin-Dependent/SU; Diabetic Angiopathies/SU; Foot/BS/SU; Human; Hypertension/PP; Injections, Intravenous; Intraoperative Complications/*DT; Ischemia/SU; Male; Propanolamines/AD/*TU. .T Bolus administration of esmolol for the treatment of intraoperative myocardial ischaemia [see comments] .P JOURNAL ARTICLE. .W We report the successful treatment with esmolol of intraoperative myocardial ischaemia associated with concurrent hypertension and tachycardia, in a patient with risk factors for coronary artery disease undergoing peripheral vascular surgery. The pathophysiology of myocardial ischaemia, and the therapeutic role of beta blocking drugs are briefly reviewed. Esmolol, a short-acting cardioselective beta blocking drug, was administered in a bolus of 1.5 mg.kg-1, and resulted in prompt resolution of the haemodynamic abnormalities, with concomitant restitution of the ST segments to isoelectric baseline. We conclude that bolus administration of esmolol is practical and can be effective for the treatment of intraoperative myocardial ischaemia. .A Miller DR; Martineau RJ. .I 200661 .U 90003555 .S Can J Anaesth 9001; 36(5):598, 600 .M Adult; Anesthesia, Epidural/*IS; Anesthesia, Obstetrical/*IS; Case Report; Catheterization/*IS; Epidural Space; Equipment Failure; Female; Human; Needles/AE; Pregnancy. .T Failure to cannulate the epidural space [letter] .P LETTER. .A Vohra A; Pollard BJ. .I 200662 .U 90003556 .S Can J Anaesth 9001; 36(5):600 .M Adult; Analgesia, Epidural/*; Case Report; Female; Human; Meperidine/*TU; Myasthenia Gravis/PP/*SU; Pain, Postoperative/*DT; Sternum/SU; Thymectomy. .T Postoperative analgesia in myasthenia gravis [letter] .P LETTER. .A Keith IC; Clark AG; John S. .I 200663 .U 90003557 .S Can J Anaesth 9001; 36(5):601 .M Cricoid Cartilage/*; Gastroesophageal Reflux/ET; Human; Intubation, Intratracheal/*AE/MT; Laryngeal Cartilages/*; Pressure. .T Cricoid pressure [letter; comment] .P COMMENT; LETTER. .A Williamson R. .I 200664 .U 90003559 .S Can J Anaesth 9001; 36(5):602-3 .M Human; Kidney Failure, Chronic/ME/*PP; Vecuronium/*AE/PK. .T Should vecuronium be used in renal failure? [letter; comment] .P COMMENT; LETTER. .A Pollard BJ; Doran BR. .I 200665 .U 90003560 .S Can J Anaesth 9001; 36(5):603-4 .M Adolescence; Air; Anesthesia, Epidural/*AE; Anesthesia, Obstetrical/*AE; Epidural Space/RA; Female; Groin; Human; Pregnancy. .T Epidural air-filled bubbles and unblocked segments [letter] [see comments] .P LETTER. .A Boezaart AP; Levendig BJ. .I 200666 .U 90003561 .S Can J Anaesth 9001; 36(5):604-5 .M Adult; Anesthesia, Epidural; Anesthesia, Intravenous; Human; Hypertension/*ET; Lithotripsy/*AE; Middle Age; Preanesthetic Medication; Quadriplegia/*/PP; Retrospective Studies. .T Autonomic hyperreflexia during extracorporeal shock-wave lithotripsy (ESWL) in quadriplegic patients [letter] [see comments] .P LETTER. .A Chen L; Castro AD. .I 200667 .U 90003641 .S Circ Res 9001; 65(4):1021-8 .M Adenosine Triphosphate/AI; Anesthetics/*PD; Animal; Calcium/ME; Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone/PD; Carrier Proteins/*AI; Cells, Cultured; Kinetics; Mitochondria, Heart/ME; Myocardium/CY/*ME; Oligomycins/PD; Rotenone/PD; Sodium/AI/ME; Support, U.S. Gov't, P.H.S.. .T Inhibition of Na-Ca exchange by general anesthetics. .P JOURNAL ARTICLE. .W General anesthetics, typically octanol, were found to inhibit the influx of calcium in isolated sodium-loaded adult rat heart cells, using 45Ca, quin 2, or indo 1. Inhibition by octanol, like inhibition by sodium, was competitive with calcium. Octanol and sodium together inhibited calcium influx synergistically. At physiological levels of extracellular calcium and sodium, the EC50 was 177 +/- 37 microM for octanol and 48 +/- 5 microM for decanol. These values are threefold to fourfold larger than those reported to cause 50% loss of righting reflex in tadpoles, a measure of their anesthetic effectiveness. We conclude that general anesthetics inhibit Na-Ca exchange at the sarcolemma. We suggest that octanol inhibits like sodium, and the synergism stems from the cooperativity of sodium inhibition at the binding and regulatory sites of the exchanger. Insofar as Na-Ca exchange may regulate inotropy, the inhibition of Na-Ca exchange by general anesthetics could contribute to their negative inotropic effect. .A Haworth RA; Goknur AB; Berkoff HA. .I 200668 .U 90003642 .S Circ Res 9001; 65(4):1029-44 .M Aequorin/DU; Animal; Anoxia/*ME/PP; Calcium/*ME; Coronary Disease/*ME/PP; Ferrets; Hemodynamics; In Vitro; Intracellular Membranes/*ME; Ions; Male; Myocardial Reperfusion/*; Myocardium/*ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Direct measurement of changes in intracellular calcium transients during hypoxia, ischemia, and reperfusion of the intact mammalian heart. .P JOURNAL ARTICLE. .W In studies of ischemia and reperfusion, a major experimental problem has been the inability to measure intracellular ionized calcium ([Ca2+]i) in the intact heart. We have developed a new approach in which the bioluminescent calcium indicator aequorin is used to measure [Ca2+]i in the isolated, coronary-perfused ferret heart. Aequorin is loaded into subepicardial myocytes of the left ventricle, and the signals are recorded simultaneously along with isovolumic left ventricular (LV) pressure at a constant pacing rate. This system shows 1) no attenuation or change of time course of LV pressure development or coronary perfusion pressure after aequorin loading; 2) consistent responses to physiological interventions and drugs; 3) individual aequorin and pressure signals that do not require signal averaging for analysis; and 4) [Ca2+]i levels comparable with those reported in tissue or isolated myocyte cell preparations. During 5 minutes of hypoxia, diastolic [Ca2+]i and LV diastolic pressure increased while the systolic values of both [Ca2+]i and pressure decreased. The peak-to-peak systolic [Ca2+]i versus LV isovolumic pressure relation remained close to the control curve. In contrast, during 3 minutes of global ischemia, LV systolic and diastolic pressures fell rapidly, while [Ca2+]i increased substantially. The [Ca2+]i versus pressure relations for both systole and diastole shifted to the right, indicating desensitization of the contractile apparatus to [Ca2+]i. These results provide evidence that different primary mechanisms determine the systolic and diastolic responses to acute hypoxia versus ischemia. During hypoxia, changes in [Ca2+]i handling probably play a major role, while during ischemia, changes in the Ca2+ sensitivity of the myofilaments appear to be of primary importance in the modulation of contractile dysfunction. .A Kihara Y; Grossman W; Morgan JP. .I 200669 .U 90003643 .S Circ Res 9001; 65(4):1045-56 .M Animal; Calcium/*PH; Carrier Proteins/PH; Coronary Disease/*PP; Heart/*PP; Heart Ventricle; Intracellular Membranes/*ME; Male; Myocardial Reperfusion/*; Rats; Rats, Inbred Strains; Sodium/*PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Role of intracellular Na+ in Ca2+ overload and depressed recovery of ventricular function of reperfused ischemic rat hearts. Possible involvement of H+-Na+ and Na+-Ca2+ exchange. .P JOURNAL ARTICLE. .W The roles of H+-Na+ and Na+-Ca2+ exchange in the depression of ventricular function were studied in the reperfused isolated ischemic rat heart. Zero-flow global ischemia was induced for either 15 or 30 minutes and was followed by 30 minutes of aerobic reperfusion. Intracellular Na+ (Na+i) and 45Ca2+ uptake were measured during ischemia and reperfusion. Accumulation of Na+i was modified by prior glycogen depletion and by treatment with amiloride, a H+-Na+ exchange inhibitor, or monensin, a Na+ ionophore. Na+i rose continuously during ischemia and rapidly during the first two minutes of reperfusion. The larger inhibitory effect of amiloride and preischemic glycogen depletion was on Na+i accumulation during reperfusion; this finding suggests that the uptake occurs by H+-Na+ exchange. Reduction of Na+i accumulation by glycogen depletion was associated with less lactate and, presumably, H+ production and accumulation during ischemia. The rapid increase in Na+i during early reperfusion may reflect the readjustment of the low intracellular pH resulting from ischemia. The level of Na+i at the end of ischemia and especially after two minutes of reperfusion were linearly correlated with 45Ca2+ uptake and depression of ventricular function during subsequent reperfusion. This highly significant correlation between Na+i and 45Ca2+ uptake when Na+i was varied by several independent procedures, including monensin, strongly suggests that reperfusion 45Ca2+ uptake occurs at least in part by Na+-Ca2+ exchange. The rate of 45Ca2+ uptake during reperfusion was linearly and highly significantly correlated with elevation of diastolic pressure, reduced developed pressure, and decreased recovery of ventricular function. The data strongly support a mechanism of ischemic cell damage that involves excessive production and accumulation of H+ during ischemia that exchanges for extracellular Na+ during ischemia and rapidly during the first few minutes of reperfusion. Increased Na+i then causes excessive 45Ca2+ uptake and depressed recovery of cellular functions with continued reperfusion. Increased levels of Na+i may be a major event that couples a decreased intracellular pH during ischemia to excessive 45Ca2+ uptake and depressed recovery of cellular function with reperfusion. .A Tani M; Neely JR. .I 200670 .U 90003644 .S Circ Res 9001; 65(4):1057-65 .M Animal; Aorta/*CY; Biogenic Amines/*PD; Blood Platelets/*ME; Cattle; Cell Movement/DE; Cells, Cultured; Endothelium, Vascular/*CY; Growth Substances/*PD; Muscle, Smooth, Vascular/*CY; Platelet-Derived Growth Factor/PD; Support, U.S. Gov't, P.H.S.; Transforming Growth Factors/PD. .T Effect of platelet factors on migration of cultured bovine aortic endothelial and smooth muscle cells. .P JOURNAL ARTICLE. .W Endothelial cell (EC) injury and the response of EC and smooth muscle cells (SMCs) to injury contribute to the pathophysiology in patients with vascular disease and atherosclerosis. Since platelets have been suggested to play an important role in modulating vascular injury, the present study was undertaken to examine the influence and mechanism of action of individual platelet factors on bovine aortic EC and SMC migration using an in vitro wound assay system. Serotonin decreased EC proliferation and reduced EC migration 21 +/- 1% (p less than 0.005), which was attenuated by imipramine. Transforming growth factor-beta reduced EC proliferation and decreased EC migration 52 +/- 3% (p less than 0.005). Norepinephrine increased EC proliferation but decreased EC migration 26 +/- 2% (p less than 0.005), which was abolished by phenoxybenzamine. Histamine increased EC proliferation but reduced EC migration 29 +/- 2% (p less than 0.005), which was attenuated by diphenhydramine. Platelet-derived growth factor decreased EC proliferation and decreased EC migration 40 +/- 2% (p less than 0.005). In contrast, serotonin increased SMC proliferation and increased SMC migration 31 +/- 2% (p less than 0.005), which was abolished by ketanserin. Transforming growth factor-beta increased SMC migration 35 +/- 5% (p less than 0.005). Norepinephrine increased SMC proliferation and increased SMC migration 43 +/- 4% (p less than 0.005), which was abolished by propranolol. Histamine increased SMC proliferation and increased SMC migration 38 +/- 3% (p less than 0.005), which was abolished by cimetidine. Platelet-derived growth factor increased SMC proliferation and increased SMC migration 40 +/- 3% (p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) .A Bell L; Madri JA. .I 200671 .U 90003645 .S Circ Res 9001; 65(4):1066-77 .M Acetylcholine/PD; Adenosine/*PD; Adenosine Cyclic Monophosphate/ME; Animal; Cell Membrane/ME; Guinea Pigs; Isoproterenol/PD; Myocardium/CY/*ME/UL; Phenylisopropyladenosine/PD; Receptors, Purinergic/DE/*ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Theophylline/*PD; Up-Regulation (Physiology)/*DE. .T Enhanced sensitivity of heart cells to adenosine and up-regulation of receptor number after treatment of guinea pigs with theophylline. .P JOURNAL ARTICLE. .W Experiments were carried out in hearts from guinea pigs that were fed either the adenosine receptor antagonist theophylline (0.6 mg/ml) or no drug. The A1 adenosine receptor radioligand [125I]aminobenzyladenosine bound to a single affinity class of receptors in heart cell membranes from control animals with Bmax and KD of 18.3 +/- 1.0 fmol/mg protein and 3.7 +/- 0.6 nM, respectively (n = 8). Heart cell membranes from animals fed theophylline for 2, 7, and 14 days bound the radioligand with about the same affinity, but the number of binding sites was significantly increased (p less than 0.01) to 30.6 +/- 1.7 (n = 3), 30.0 +/- 0.8 (n = 3), and 27.3 +/- 2.9 (n = 4), respectively. Nearly identical results were obtained with membranes prepared from enzymatically dispersed ventricular myocytes. Fourteen days of theophylline treatment also produced a small increase (12%, p less than 0.01) in the number of binding sites in membranes derived from cerebral cortexes. Isolated ventricular myocytes prepared from animals fed no drug or theophylline for 7 days were used to determine the effect of adenosine on 20 nM isoproterenol-stimulated calcium current (ICa) measured by the whole-cell patch-clamp technique. Adenosine reduced isoproterenol-stimulated ICa without affecting the activation or inactivation kinetics of the current; ICa density was reduced less by 5 microM adenosine in cells from control (25 +/- 3 to 21 +/- 3 microA/microF) than in cells from theophylline-fed animals (26 +/- 5 to 17 +/- 2 microA/microF). Although a high concentration (0.5 mM) of adenosine abolished isoproterenol-stimulated ICa in cells from control or theophylline-fed animals, the IC50 for adenosine was sixfold less in cells derived from theophylline-fed animals than in cells from control animals (4.6 +/- 0.6 microM and 28.3 +/- 1.4 microM, respectively, p less than 0.01). In contrast, the increase in ICa in response to isoproterenol alone and the potency of acetylcholine to antagonize this effect of isoproterenol were the same in both groups of cells. A maximally effective concentration of R-phenylisopropyladenosine (0.1 mM) inhibited isoproterenol-stimulated cyclic AMP accumulation less in cardiomyocytes from control than from theophylline-fed animals (28.7 +/- 1.8% vs. 42.0 +/- 4.2%, p less than 0.05). In summary, exposure of the myocardium to theophylline increases the number of adenosine receptors and the effects of receptor occupancy by agonists. These findings imply that the endogenous concentration of adenosine is high enough in the normoxic guinea pig heart to chronically maintain adenosine receptors in a partially down-regulated state. .A Wu SN; Linden J; Visentin S; Boykin M; Belardinelli L. .I 200672 .U 90003648 .S Circ Res 9001; 65(4):1094-101 .M Animal; Coronary Disease/PP; Fatty Acids/AI; Glucose/*ME; Glycine/PD; Glycogen/ME; Heart/PP; Myocardial Contraction; Myocardial Reperfusion/*; Myocardium/*ME; Oxidation-Reduction; Oxygen Consumption; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Swine. .T Metabolic oxidation of glucose during early myocardial reperfusion. .P JOURNAL ARTICLE. .W We have previously studied the relation between long-chain fatty acid and pyruvate metabolism in reperfused myocardium and noted a rapid return of fatty acid oxidation to at least preischemic values accompanied by a marked decrease in pyruvate oxidation. The purpose of the present report is to further characterize carbohydrate metabolism during reflow by describing rates of glucose oxidation using [6-14C]glucose. Oxidative performance was determined with and without preserved fatty acid utilization; the latter condition was effected by oxfenicine, which inhibits palmitoylcarnitine transferase I. In the main protocol, two groups of working swine hearts (n = 18) were perfused aerobically for 30 minutes, rendered regionally ischemic (-60 delta % in anterior descending coronary flow) for 45 minutes, and reperfused at control flows for a final 50 minutes of perfusion. An emulsion of Intralipid with heparin was administered systemically throughout the studies to augment serum fatty acids (average fatty acid values, 1.05 +/- 0.05 mumol/ml for both groups). Serum glucose was monitored and maintained at or about 100 mg/dl with additional infusions of glucose as needed. Oxfenicine (33 mg/kg) was administered systemically by bolus injection at time 0 and 60 minutes of perfusion in nine animals. Decreased mechanical performance, that is, stunning, during reflow was evident in both groups (-50 delta % in regional systolic shortening, p less than or equal to 0.05 compared with aerobic values in the control group, and -32 delta %, p less than or equal to 0.05 compared with aerobic values in treated hearts).(ABSTRACT TRUNCATED AT 250 WORDS) .A Renstrom B; Nellis SH; Liedtke AJ. .I 200673 .U 90003649 .S Circ Res 9001; 65(4):1102-11 .M Animal; Biomechanics; Cell Separation; Electrophysiology; Female; In Vitro; Male; Membrane Potentials/DE; Minoxidil/*AA/PD; Muscle, Smooth, Vascular/CY/DE; Norepinephrine/AI/PD; Ouabain/PD; Portal Vein/CY/*DE/PH; Rabbits; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tetraethylammonium Compounds/PD; Vasoconstriction; Vasodilation. .T Electrophysiological mechanisms of minoxidil sulfate-induced vasodilation of rabbit portal vein. .P JOURNAL ARTICLE. .W The electrophysiological and mechanical properties of the vasodilator minoxidil sulfate (MNXS) were examined in isolated smooth muscle cells and strips from rabbit portal vein. At micromolar concentrations, MNXS inhibited norepinephrine (0.1-1.0 microM)-induced contractions in isolated muscle strips. In isolated cells, norepinephrine caused a dose-dependent depolarization of the resting membrane potential, which was significantly attenuated by MNXS (5 microM); MNXS alone caused a hyperpolarization of the membrane potential. This hyperpolarization was insensitive to Na+-K+ pump blockade by ouabain, but was inhibited by the K+ channel antagonist, tetraethylammonium (20 mM). In voltage-clamp experiments, a resting (background) conductance associated with the resting membrane potential was identified. This conductance, which previously has been shown to be reduced by Ba2+ as well as tetraethylammonium, was increased by MNXS (2 microM). In additional experiments, whole-cell L-type Ca2+ currents were inhibited by micromolar concentrations of MNXS. These experiments show that concentrations of MNXS that inhibit norepinephrine-induced contractions promote K+ conductance and inhibit Ca2+ entry through voltage-dependent Ca2+ channels in vascular smooth muscle cells. These electrophysiological effects of MNXS may be responsible for the vasorelaxant effects of the drug observed in vitro and in vivo. .A Leblanc N; Wilde DW; Keef KD; Hume JR. .I 200674 .U 90003650 .S Circ Res 9001; 65(4):1112-24 .M Animal; Antibodies, Monoclonal/AN/*IM; Coronary Circulation; Dogs; Heart/PP; Hemodynamics; Immunoglobulins, Fab/*IM; Leukocyte Count; Myeloperoxidase/ME; Myocardial Reperfusion Injury/PA/*PC/PP; Support, U.S. Gov't, P.H.S.; Systole. .T F(ab')2 fragments of anti-Mo1 (904) monoclonal antibodies do not prevent myocardial stunning. .P JOURNAL ARTICLE. .W To determine if inhibition of leukocyte adhesion and aggregation could improve postischemic ventricular dysfunction ("stunning"), a monoclonal antibody (904) that binds to the adhesion-promoting Mo1 glycoprotein on the cell surface of leukocytes was administered intravenously (0.5 mg/kg) to open-chest dogs before a 15-minute coronary occlusion. Ultrasonic crystals placed in ischemic and control myocardium were used to measure systolic wall thickening during a 15-minute occlusion of the left anterior descending artery and for 3 hours after reperfusion. Myocardial blood flow was measured with tracer-labeled microspheres before occlusion, after 10 minutes of occlusion, 3 minutes of reperfusion, and at 1 and 3 hours after reperfusion. Six animals receiving anti-Mo1 antibody had antibody excess demonstrated with immunofluorescence techniques at 5 minutes and 3 hours of reperfusion; this finding indicated saturation of binding sites. Five animals served as controls and received an antibody (murine immunoglobulin G) that does not influence neutrophils. The two groups did not differ hemodynamically during ischemia and reperfusion. Risk areas and myocardial blood flow were also not significantly different between the two groups. The main parameter used to define regional myocardial stunning, percentage systolic wall thickening in the ischemic/reperfused area, did not differ significantly between the two groups. Specimens from nonischemic myocardium were compared with ischemic specimens for myeloperoxidase content. There were no significant differences within or between groups. These data indicate that the anti-Mo1 monoclonal antibody (904) is not effective in improving the profound myocardial dysfunction that persists for 3 hours of reperfusion after 15 minutes of ischemia. .A Schott RJ; Nao BS; McClanahan TB; Simpson PJ; Stirling MC; Todd RF 3d; Gallagher KP. .I 200675 .U 90003651 .S Circ Res 9001; 65(4):1125-35 .M Animal; Biomechanics; Bromodeoxyuridine/DU; Cattle/BL; Culture Media; DNA/BI; Endothelium, Vascular/PH; Male; Rats; Rats, Inbred WKY; Renal Artery/ME/*PH; Serotonin/PH; Support, Non-U.S. Gov't; Time Factors; Tissue Culture; Vasoconstriction/*. .T Acute and long-term effects of tissue culture on contractile reactivity in renal arteries of the rat. .P JOURNAL ARTICLE. .W To evaluate long-term effects of contractile and mitogenic stimuli on the contractile reactivity of arterial smooth muscle, we measured the incorporation of the thymidine analogue 5-bromo-2'-deoxyuridine (BrdUrd) and mechanical responses in arterial segments that had been maintained in tissue culture. The experiments were performed on renal arteries that had been isolated from adult rats, chemically sympathectomized, mechanically denuded from endothelium and mounted under distension. Exposure of arterial segments for up to 3 weeks to culture medium supplemented with fetal calf serum resulted in the following consecutive changes: a strong acute contraction, selective pharmacological changes that included decreased contractile responses to phenylephrine and vasopressin and increased relaxing responses to isoproterenol, increased incorporation of BrdUrd, a progressive fall in contractile responses to all vasoconstrictor stimuli, and an increase in excitability. Serum-free medium resulted in a much smaller acute arterial contraction, induced less incorporation of BrdUrd, accelerated the occurrence of hyperexcitability, but did not affect early pharmacological changes or the subsequent fall in overall arterial contractility with tissue culture. Dialysis of the serum or addition of ketanserin abolished the contractile effect of serum but did not affect the incorporation of BrdUrd or the loss of contractility with tissue culture. Addition of serotonin to serum-free culture medium mimicked the contractile response to serum but not the stimulation of BrdUrd incorporation. These data indicate that tissue culture alters the properties of the arterial wall, that contraction does not underlie the proliferative response of arterial smooth muscle to serum-derived mitogens in vitro, and that stimulation of DNA synthesis does in itself not lead to selective changes in arterial contractility. .A De Mey JG; Uitendaal MP; Boonen HC; Vrijdag MJ; Daemen MJ; Struyker-Boudier HA. .I 200676 .U 90003653 .S Circ Res 9001; 65(4):1141-4 .M Adult; Calcium/*ME; Cardiac Output, Low/ME; Cardiomyopathy, Congestive/*ME; Heart Ventricle; Human; Middle Age; Myocardium/*ME; Receptors, Adrenergic, Beta/ME; Reference Values; Sarcoplasmic Reticulum/*ME; Support, U.S. Gov't, P.H.S.. .T Ca2+ uptake by cardiac sarcoplasmic reticulum from patients with idiopathic dilated cardiomyopathy. .P JOURNAL ARTICLE. .W We measured Ca2+ uptake by sarcoplasmic reticulum prepared from left ventricular myocardium obtained from six nonfailing human hearts and nine excised hearts from patients with class IV idiopathic dilated cardiomyopathy. Ca2+ uptake had a Vmax of 593 +/- 82 nmol/mg-min, a K0.5 of 0.68 +/- 0.07 microM, and an nHill of 1.7 +/- 0.1 in the nonfailing hearts. The corresponding values in the excised failing hearts were 593 +/- 36 nmol/mg-min, 0.63 +/- 0.03 microM, and 1.6 +/- 0.1. The beta-receptor density in crude sarcolemma prepared from left ventricular myocardium was 110.0 +/- 15.3 fmol/mg in the unmatched donors and 52.1 +/- 4.5 fmol/mg in the excised failing hearts. These results suggest that abnormal Ca2+ handling in idiopathic dilated cardiomyopathy in humans is not the result of any intrinsic alteration of Ca2+ uptake by sarcoplasmic reticulum. .A Movsesian MA; Bristow MR; Krall J. .I 200677 .U 90003655 .S Circ Res 9001; 65(4):1151-6 .M Animal; Biomechanics; Carbon; Chemistry; Electron Spin Resonance; Free Radicals/*; Hydroxides/ME; Lipid Peroxides/*AI/BI; Propranolol/*PD; Sarcolemma/*ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Inhibition of sarcolemmal carbon-centered free radical formation by propranolol. .P JOURNAL ARTICLE. .W The mechanism of propranolol-inhibited sarcolemmal membrane lipid peroxidation was investigated by electron spin resonance spin-trapping technique using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and 2-methyl-2-nitrosopropane (MNP). Highly purified canine myocytic sarcolemma were peroxidized by a superoxide-driven (from dihydroxyfumarate) and Fe3+-catalyzed free radical-generating system. Hydroxyl radicals (.OH), identified by electron spin resonance signals as DMPO-OH adducts, were generated in the aqueous phase. Propranolol up to 500 microM did not effectively reduce the intensity of the DMPO-OH adducts. When the sarcolemma were incubated with MNP before the addition of free radicals, MNP adducts characteristic of carbon-centered radicals were produced. Pretreatment of the membranes with propranolol (3-100 microM) decreased the intensity of the MNP adducts in a log concentration-dependent manner; the EC50 is about 7 microM. D- and L-propranolol were found equally effective. When protein-depleted sarcolemmal lipids were similarly incubated with MNP and the free radical system, identical MNP adducts were observed; this finding suggests that the adducts were lipid-derived products arising from lipid peroxidation. Furthermore, their formation was also inhibited by propranolol pretreatment. Since propranolol is not an effective scavenger of oxygen radicals in the aqueous phase, the data suggest that the antiperoxidative effect of propranolol is due to its lipophilic interaction with the membrane and thus subsequent interruption of the free radical chain reactions. .A Mak IT; Arroyo CM; Weglicki WB. .I 200678 .U 90003656 .S Circ Res 9001; 65(4):1157-60 .M Adenosine Triphosphate/AI/*PD; Animal; Anti-Arrhythmia Agents/*PD; Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone/PD; Guinea Pigs; Myocardium/CY/*ME; Ouabain/ME; Potassium Channels/*DE/ME; Rats; Rotenone/PD; Rubidium/ME; Support, U.S. Gov't, P.H.S.. .T Inhibition of ATP-sensitive potassium channels of adult rat heart cells by antiarrhythmic drugs. .P JOURNAL ARTICLE. .W We have investigated the effect of antiarrhythmic drugs on the increased potassium conductance induced in isolated adult rat heart cells by ATP depletion. The rate of 86Rb uptake in the presence of ouabain was used as a measure of potassium conductance. Treatment of cells with rotenone plus p-trifluoromethoxyphenylhydrazone (FCCP) rapidly depleted ATP levels and strongly stimulated the rate of 86Rb uptake. The stimulated uptake and the ATP depletion were inhibited by oligomycin; thus, the uptake was not induced by rotenone plus FCCP directly. The stimulated uptake, but not the ATP depletion, was inhibited potently by glyburide (IC50, 38.3 nM), quinidine (IC50, 2.7 microM), verapamil (IC50, 4.5 microM), and amiodarone (IC50, 19.1 microM). The stimulated uptake was also inhibited by tetraethylammonium ion and by 4-aminopyridine but not by tetrodotoxin or manganese. We conclude that 1) the stimulated 86Rb uptake is measuring ATP-sensitive potassium channel activity, 2) the ATP-sensitive potassium channel is strongly inhibited by quinidine, verapamil, and amiodarone, and 3) this inhibition may contribute to the antiarrhythmic action of these drugs. .A Haworth RA; Goknur AB; Berkoff HA. .I 200679 .U 90003658 .S Circ Res 9001; 65(4):869-79 .M Abdominal Wall/BS; Animal; Arteries/*PA/PP; Arterioles/*PA/PP; Blood Pressure; Chronic Disease; Hypertension/*PA/PP; Male; Muscle Tonus; Rats; Rats, Inbred Strains; Support, U.S. Gov't, P.H.S.. .T Effects of chronic hypertension and its reversal on arteries and arterioles. .P JOURNAL ARTICLE. .W The reversibility of functional and structural microvascular alterations in chronic renal hypertension has not been established. Twelve weeks after surgery to induce hypertension, in vivo arteriolar and venular dimensions were measured in the cremaster muscle of rats with one-kidney, one-clip hypertension (1K1C), rats in which the clip was removed after 8 weeks (1KNT), and controls. Systolic blood pressure was significantly elevated after 3 days in 1K1C rats and reached a plateau by 6 weeks. In 1KNT rats, systolic blood pressures were similar to 1K1C rats but were normalized 1 day after unclipping. A marked medial-intimal hypertrophy was found by histological techniques in the thoracic and abdominal aortae (45% and 69%, respectively) but not in cremaster feeding arteries of 1K1C rats. These arterial changes were reversed after unclipping. In 1K1C rats, medial-intimal area decreased in first- through fourth-order (1A, 2A, 3A, and 4A) arterioles along with a decline in relaxed diameter (41%, 30%, 20%, and 21%, respectively), which was only partially restored after unclipping. Heart weight was increased by 67% in 1K1C rats, but it did not differ between 1KNT and controls. Therefore, the reversal of chronic renal hypertension can normalize gross structural alterations in the heart and large vessels, but more time may be required to normalize completely the arteriolar changes. These data indicate that long-term structural adaptations in renal hypertension are different in arterioles and arteries, and they may be related to chronic changes in blood flow and/or pressure. .A Stacy DL; Prewitt RL. .I 200680 .U 90003659 .S Circ Res 9001; 65(4):880-93 .M Amantadine/*PD; Animal; Calcium/PH; Cell Membrane/PH; Cell Separation; Cesium/PD; Electrophysiology; Guinea Pigs; Heart/*PH; Heart Ventricle; Membrane Potentials/DE; Myocardium/CY/UL; Support, Non-U.S. Gov't; Time Factors. .T Amantadine-induced afterpotentials and automaticity in guinea pig ventricular myocytes. .P JOURNAL ARTICLE. .W The ionic mechanisms of amantadine-induced changes in membrane potential and automatic activity in guinea pig ventricular myocytes were studied using the suction-pipette whole-cell clamp method. While 25-100 microM amantadine decreased the action potential amplitude and duration, 200 and 400 microM amantadine lengthened the action potential duration and decreased the maximum diastolic potential with an appearance of diastolic depolarization and automaticity. In the presence of 25-100 microM amantadine, the preparations developed an afterpotential due to incomplete repolarization and a delayed afterdepolarization that eventually brought about triggered automaticity. The former type of afterpotential was abolished by tetrodotoxin (TTX) and the latter by Co2+. Spontaneous activity from the diastolic depolarization was also abolished by Co2+ but not by Cs+. Amantadine suppressed the calcium current to as much as half of the control at the concentrations used (25-200 microM). The drug also produced a depression of the inward rectifier K+ current. The outward current showing time-dependent decay was activated at the plateau voltages by concentrations lower than 100 microM, whereas the delayed outward K+ current was depressed by the drug in a concentration-dependent manner at more positive potentials. Amantadine activated the TTX-sensitive and TTX-insensitive inward currents on repolarization from depolarized states, without producing the transient inward current. These results indicate that the amantadine-induced diastolic depolarization and afterpotentials are caused by changes in multiple ionic currents and that, therefore, the drug can be used as a unique model for the study of arrhythmogenesis. .A Hiraoka M; Hirano Y; Kawano S; Fan Z; Sawanobori T. .I 200681 .U 90003660 .S Circ Res 9001; 65(4):894-902 .M Acidosis/ME/*PP; Animal; Calcium/*PH; Cell Separation; Electrophysiology; Extracellular Space/*ME; Heart Ventricle; Hydrogen/*PH; Hydrogen-Ion Concentration; Myocardial Contraction/*; Myocardium/PA; Osmolar Concentration; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Contractile shortening response of ventricular cells to extracellular acidosis. Evidence for two-site control of H+-Ca2+ interaction. .P JOURNAL ARTICLE. .W The effect of extracellular acidosis on contraction of single isolated ventricular cells from rabbit was measured in a system in which pHo could be changed in less than 200 msec. The contractile response to acidotic levels was complete within 25 seconds. The response was measured 30 seconds after pHo was decreased to 7.0, 6.5, 6.0, and 5.5 at each of 8 [Ca]o levels (0.125-4.0 mM). Cell shortening versus [Ca]o was plotted to construct a curve for each pHo level, with each point relative to shortening at pH 7.5, [Ca]o = 1 mM (100% value). Calcium current (1 mM [Ca]o) was also measured 30 seconds after pHo was decreased from 7.5 to 6.5 with single-cell patch clamp technique. The contractile response to extracellular acidosis is accurately predicted by assuming two (probably sarcolemmal) sites at which H+ ions affect calcium binding and/or flux: (equation; see text) The first factor represents a set of sites that are proposed to control access, dependent on the degree of their ionization, to sites represented by the second factor. The latter sites are proposed to accept calcium according to mass-action law. The response of calcium channel current to extracellular acidosis was also complete and reversible within 25 seconds. The current response indicates that the two-site model could be predictive for the effect of extracellular acidosis on calcium current in ventricular cells. .A Langer GA; Rich TL; Ji S. .I 200682 .U 90003661 .S Circ Res 9001; 65(4):903-8 .M Animal; Biomechanics; Cattle; Electric Stimulation; Endothelium, Vascular/PH; Guanethidine/PD; In Vitro; Mesenteric Arteries/DE/*PH; Nervous System/*PH; Phenylephrine/PD; Stimulation, Chemical; Support, Non-U.S. Gov't; Tetrodotoxin/PD; Vasoconstriction; Vasodilation/*. .T A novel neurogenic vasodilator mechanism in bovine mesenteric artery. .P JOURNAL ARTICLE. .W The presence of a neurogenic vasodilator mechanism was investigated in isolated bovine mesenteric arteries (BMAs) that were precontracted with phenylephrine. Electrical field stimulation induced tetrodotoxin-sensitive relaxations in guanethidine-pretreated BMAs. The relaxation occurred after a delay of about 5-8 seconds and amounted to 25-35% in different sets of experiments. The relaxation was not affected by classical receptor antagonists such as atropine (1 microM), cimetidine (3.9 microM), clemastine (2.8 microM), naloxone (1.2 microM), 8-phenyltheophylline (1 microM), propranolol (3.4 microM), ritanserin (5 microM), or droperidol (13 microM). The nicotinic acetylcholine-receptor stimulant 1,1-dimethyl-4-phenyl-piperazinium iodide (10 microM) was without effect on the relaxation, and removal of the endothelium of the arteries also had no effect. The bee venom component apamin (1 microM), which has been shown to block the nonadrenergic, noncholinergic relaxation in intestinal and vascular smooth muscle from other species, was also found to be without effect on the relaxation induced by electrical field stimulation in BMAs. Pretreatment of the arteries with capsaicin (1 microM) had no effect per se and did not affect the relaxation induced by a subsequent stimulation. Capsaicin has been suggested to release neurotransmitter and eventually deplete neurons containing substance P and calcitonin gene-related peptide. Furthermore, exogenously applied calcitonin gene-related peptide (1-100 nM), substance P (10 nM-1 microM), and vasoactive intestinal peptide (0.3-30 nM) gave relaxations amounting to less than 10%. It is postulated that electrical field stimulation induces a neurogenic relaxation of a nonadrenergic, noncholinergic nature in BMAs.(ABSTRACT TRUNCATED AT 250 WORDS) .A Axelsson KL; Ljusegren ME; Ahlner J; Grundstrom N. .I 200683 .U 90003662 .S Circ Res 9001; 65(4):909-16 .M Acidosis/*ME; Animal; Biological Availability; Electric Stimulation; Energy Metabolism; Heat; Hydrogen/*PD; Hydrogen-Ion Concentration; Myocardium/*ME; Oxygen/*PK; Rabbits. .T Metabolic recovery of acidotic rabbit cardiac muscle: effects of low pH and oxygen shortage. .P JOURNAL ARTICLE. .W Heat production during and after contraction of isolated rabbit papillary muscles was measured at 20 degrees C with metal-film thermopiles. Under control conditions (0.2 Hz, pH 7.4) total heat and steady-state force production due to 120 twitches were 1.0 +/- 0.4 J/g and 29.5 +/- 5.1 mN/mm2 (mean +/- SD; n = 5), respectively. Increasing the CO2 of the bicarbonate-buffered superfusate from 5% (pH 7.4) to 24% (pH 6.6) led to a decrease of force and heat production, 54% and 72%, respectively, of the control value. The recovery heat-time constant, reflecting the time course of oxidative phosphorylation, increased from 23.0 +/- 5.1 seconds at pH 7.4 to 69.5 +/- 34.7 seconds at pH 6.6. The ratio of recovery and initial heat equaled 1.06 under both conditions. Enhancing the metabolic rate by increasing the stimulation frequency to 1.0 Hz led, after an initial maximum, to a decline of force and heat presumably as the consequence of shortage of oxygen in the muscle core. The recovery phase in this case was characterized by a double exponential function having time constants of 7.6 and 64.4 seconds. When pH was lowered to 6.6 together with the enhancement of the stimulation frequency to 1 Hz, an additional exothermal process, unrelated to force production, was observed during contraction and for some time thereafter. It was concluded that severe acidosis slows down the rate of oxidative phosphorylation and may reduce the economy of contraction. However, it does not change the nature of recovery and initial heat processes.(ABSTRACT TRUNCATED AT 250 WORDS) .A Mast F; Elzinga G. .I 200684 .U 90003663 .S Circ Res 9001; 65(4):917-24 .M Animal; Anions/ME; Aorta/PH; Endothelium-Derived Relaxing Factor/PH; Endothelium, Vascular/*PH; Free Radicals; Hydroxides/PD; In Vitro; Muscle, Smooth, Vascular/*PH; Neutrophils/ME/*PH; Rabbits; Superoxide/ME; Vasoconstriction/*/DE. .T Rabbit polymorphonuclear neutrophils elicit endothelium-dependent contraction in vascular smooth muscle. .P JOURNAL ARTICLE. .W The present studies were designed to investigate the interaction between activated polymorphonuclear neutrophils (PMNs) and endothelial regulation of vascular smooth muscle function. Rabbit peritoneal PMNs (4 x 10(3)-4 x 10(5) cells/ml) added to muscle bath chambers containing phenylephrine-precontracted rabbit isolated aortic rings produced no effect on vascular tone. However, when PMNs were activated with the chemotactic peptide, f-met-leu-phe (0.1 microM), PMNs produced concentration-dependent vascular contraction, which was dependent on the presence of the endothelium. Aortic rings denuded of endothelium were unaffected by activated PMNs. Superoxide dismutase (100 units/ml) treatment of tissues blocked completely PMN-induced vascular contraction, whereas mannitol (20 mM) had no significant effect on PMN-induced vascular contraction. Pyrogallol (a generator of superoxide anion) produced a response that was similar to that observed with activated PMNs. Superoxide anion production was measured separately, and the time of peak rate of superoxide anion production corresponded to the time of the maximal vascular contractile responses. Activated PMNs added to vascular tissues undergoing endothelium-dependent relaxation mediated by either acetylcholine or A23187 produced a reversal of vascular relaxation. Furthermore, activated PMNs did not have any effect on endothelium-independent vascular relaxation produced by either isoproterenol or nitroglycerin. The present investigation reveals that activated PMNs can release superoxide anion and produce endothelium-dependent contraction. The endothelium-dependent contraction may be the result of superoxide anion inactivation of endothelium-derived relaxing factor. .A Ohlstein EH; Nichols AJ. .I 200685 .U 90003664 .S Circ Res 9001; 65(4):925-33 .M Animal; Argipressin/*PD; Blood Pressure/DE; Brain/*PH; Cardiovascular System/*DE; Cisterna Magna; Consciousness; Heart Rate/DE; Injections; Injections, Intraventricular; Male; Pressoreceptors/DE; Rats; Rats, Brattleboro; Rats, Inbred Strains; Reference Values; Reflex/DE; Support, Non-U.S. Gov't. .T Differential cardiovascular effects of centrally administered vasopressin in conscious Long Evans and Brattleboro rats. .P JOURNAL ARTICLE. .W The cardiovascular effects of arginine vasopressin (AVP) administered into a lateral cerebral ventricle or into the cisterna magna were investigated in conscious Long Evans (control) rats and AVP-deficient Brattleboro rats. The effects of subpressor intracerebroventricular and intracisternal doses of AVP on cardiac baroreflex sensitivities were also determined. Intracerebroventricular and intracisternal AVP increased blood pressure of both strains of rat in a dose-dependent manner. The maximum pressor response produced by intracerebroventricular AVP in Long Evans rats was 13 +/- 2/13 +/- 1 mm Hg (systolic/diastolic, n = 6) after 100 ng AVP. The pressor response to the highest intracerebroventricular dose of AVP tested in Brattleboro rats (30 ng) was 46 +/- 13/21 +/- 6 mm Hg (n = 6). Intracerebroventricular AVP caused a tachycardia in Brattleboro rats but had no effect on heart rate of Long Evans rats. At doses greater than 1 ng, the increases in blood pressure produced by intracisternal AVP in both groups of rats were significantly greater than the increases produced by the same doses given intracerebroventricularly. Heart rate fell in a dose-dependent manner after intracisternal AVP in Long Evans rats but not in Brattleboro rats. Cardiac baroreflex sensitivities of Brattleboro rats were not significantly different from those of Long Evans rats and were not modified by intracerebroventricular (0.3 ng) or intracisternal (0.1 ng) AVP. In Long Evans rats, intracisternal AVP (0.3 ng) increased cardiac baroreflex responses to both increases and decreases in pressure. Intracerebroventricular AVP (0.3 ng) increased the sensitivity of the reflex in response to an elevation but not to a reduction in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) .A Harland D; Gardiner SM; Bennett T. .I 200686 .U 90003665 .S Circ Res 9001; 65(4):934-45 .M Animal; Antigens, Differentiation/*AN; Blood/MI; Blood Cells/IM/PA; Coxsackie B Viruses/IP; Coxsackievirus Infections/*; Cyclosporins/*PD; Lymphocytes/*IM/PA; Mice; Myocarditis/*ET/MO/PA; Myocardium/*PA; Organ Weight; Support, Non-U.S. Gov't. .T Absence of effects of cyclosporine on myocardial lymphocyte subsets in Coxsackievirus B3 myocarditis in the aviremic stage. .P JOURNAL ARTICLE. .W To test the therapeutic efficacy of immunosuppression with cyclosporine upon the aviremic stage of coxsackievirus B3 (CB3) myocarditis, 2-week-old BALB/c mice were inoculated with 3 x 10(2) plaque-forming units of CB3, and the effects of cyclosporine on peripheral, splenic, and myocardial lymphocyte subsets were investigated. Cyclosporine, 25 mg/kg/day, was administered subcutaneously daily on days 10-31 (experiment 1) and days 30-51 (experiment 2). Treated groups were compared with infected controls for each experiment. In experiment 1, the survival rate of the cyclosporine-treated group was low (17/25 vs. 24/25, p less than 0.05). The severity of myocardial lesions and the distribution of lymphocyte subsets in myocardium and spleen on days 15-18 did not differ between treated and control groups; on the other hand, the percentages of peripheral Thy 1.2+ (pan T) and L3T4+ (activated helper T) cells on days 15-18 were decreased in the treated group, and those of B, Lyt 1+ (helper/inducer T), and Lyt 2+ (suppressor/cytotoxic T) subsets did not differ significantly. Notably, myocardial interleukin-2 receptor (IL-2R) positive cells, through which cyclosporine is considered to act, were scarce in both groups. In experiment 2, survival rates of two groups did not differ (treated, 32/34; untreated, 34/34; p = NS). The severity of myocardial lesions and the distribution of splenic lymphocyte subsets on days 35-38 also were not different between two groups. The percentages of peripheral lymphocyte subsets (Thy 1.2+ and L3T4+) were decreased in the treated group; those of B, Lyt 1+, and Lyt 2+ subsets did not differ significantly. In experiments 1 and 2, the thymus/body weight ratio in the treated groups was smaller than in the untreated group, but the spleen/body weight ratio in the treated group did not differ from the untreated group; histologically, medullary cellular depletion was evident in the thymus, not in the spleen, of the treated groups. We conclude that cyclosporine failed to change the distribution of lymphocyte subsets in the spleen as well as in the myocardium in CB3 myocarditis although it had effects on the peripheral blood and thymus, which may account for the higher mortality in the treated groups. The absence of beneficial effects of cyclosporine upon the CB3-infected myocardium may be related to the paucity of cyclosporine-sensitive cells (IL-2R, L3T4, and Lyt 2 positive cells) in the myocardium. .A Kishimoto C; Abelmann WH. .I 200687 .U 90003666 .S Circ Res 9001; 65(4):946-54 .M Air/*; Animal; Biomechanics; Cineradiography; Dogs; Lung/*PH; Pressure; Respiratory Airflow; Respiratory System/PH; Resuscitation/*/IS; Support, U.S. Gov't, P.H.S.; Thoracic Radiography; Thorax/*PH. .T Air trapping in the lungs during cardiopulmonary resuscitation in dogs. A mechanism for generating changes in intrathoracic pressure. .P JOURNAL ARTICLE. .W To test the hypothesis that during cardiopulmonary resuscitation, chest compression with an unobstructed trachea raises and maintains intrathoracic pressure by collapsing airways and trapping air in the lung, we studied 11 dogs (20-32 kg). An inflatable vest compressed the thorax after induction of ventricular fibrillation. First, tracheal airflow was measured by a pneumotachometer during vest inflation and deflation in nine of the dogs. As expected, during the initial phase of vest inflation of cycles after ventilation, air moved out of the lungs, but then airflow stopped. After vest deflation, however, more air moved out of the lungs in eight of the nine dogs; this occurrence indicated that a portion of the inspired tidal volume was trapped during vest inflation. During cycles without prior ventilation, the amount of air expired by chest compression decreased, paradoxically, at higher peak vest pressure (p less than 0.002); this occurrence indicated that air was trapped at the higher vest pressures. The change in right atrial pressure was higher on cycles after ventilation than on cycles without prior ventilation (79 +/- 12 vs. 67 +/- 12 mm Hg [mean +/- SEM], p less than 0.005), and lung volume was higher on cycles after ventilation (p less than 0.001). Next, a 5-Fr micromanometer was advanced down the airway in eight of the dogs. With the tip of the micromanometer 5-8 cm distal to the carina, a zone of high pressure was noted in seven dogs; this high pressure suggested a zone of airway collapse distal to the carina.(ABSTRACT TRUNCATED AT 250 WORDS) .A Halperin HR; Brower R; Weisfeldt ML; Tsitlik JE; Chandra N; Cristiano LM; Fessler H; Beyar R; Wurmb E; Guerci AD. .I 200688 .U 90003667 .S Circ Res 9001; 65(4):955-70 .M Action Potentials; Animal; Cell Separation; Dogs; Electrophysiology; Endocardium/*CY; Female; Heart Ventricle; Homeostasis; Male; Membrane Potentials; Microscopy, Electron; Myocardial Infarction/PA/*PP; Purkinje Cells/*PH/UL; Reaction Time; Support, U.S. Gov't, P.H.S.; Time Factors. .T Electrophysiology and ultrastructure of canine subendocardial Purkinje cells isolated from control and 24-hour infarcted hearts. .P JOURNAL ARTICLE. .W Ventricular arrhythmias that accompany myocardial infarction in dogs may be secondary to the altered electrophysiological properties of the subendocardial Purkinje fibers that survive 24 hours after the coronary occlusion. To better understand the ionic mechanisms that underlie the altered electrical activity of these fibers, we have dispersed, using an enzymatic technique, Purkinje cells from the subendocardium of the infarcted ventricle (IZPCs) and compared their electrical and structural properties to Purkinje cells dispersed from fiber strands (SPCs) and from the subendocardium of the noninfarcted ventricle (NZPCs). Ultrastructural analysis of these cells shows that IZPCs contain an increased number of lipid droplets when compared with the SPCs and NZPCs. In addition, transmembrane action potentials of IZPCs have reduced resting potentials, action potential amplitudes, and upstroke velocity and are increased in duration when compared with either SPCs or NZPCs. Input resistance of IZPCs is increased over that measured in control cells (SPCs and NZPCs). Furthermore, the time course of the process of electrical restitution of action potential duration is altered in IZPCs with long action potentials. Finally, using K+-sensitive microelectrode techniques, we have determined that intracellular free K+ activity (aKi) in IZPCs (93.7 +/- 15 mM) is not significantly different from control aKi measurements (SPC, 106 +/- 13 mM; NZPC, 103 +/- 12 mM). Thus a reduction in aKi does not provide a basis for the reduced resting potentials observed in IZPCs. By studying the relation between the resting potential and log [K+]o we determined that in IZPCs with reduced resting potentials, there is a significant increase in the PNa/PK ratio when compared with control. In summary, to better understand the cellular basis of ventricular arrhythmias postinfarction, we have developed a single cell model that will allow for more rigorous electrophysiological studies of the specific ionic currents that underlie the abnormal electrophysiology. .A Boyden PA; Albala A; Dresdner KP Jr. .I 200689 .U 90003668 .S Circ Res 9001; 65(4):971-80 .M Adenosine/PD; Animal; Blood Pressure/DE; Cardiac Output, Low/PA/*PP; Consciousness; Coronary Circulation/*/DE; Dogs; Endocardium/*PP; Female; Fibrosis; Heart/*PP; Hemodynamics; Male; Myocardium/*PA; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Subendomyocardial exhaustion of blood flow reserve and increased fibrosis in conscious dogs with heart failure. .P JOURNAL ARTICLE. .W The effects of near-maximal coronary vasodilation were examined in conscious dogs with left ventricular (LV) failure after pressure overload hypertrophy induced by either aortic banding alone or aortic banding plus a peripheral arteriovenous shunt. The findings were compared with results in littermates with compensated LV hypertrophy and with a third group of normal dogs. At rest, there was a marked difference in the intramyocardial distribution of coronary flow, measured with radiolabeled microspheres. The endocardial/epicardial (endo/epi) flow ratio in the LV failure dogs was 0.96 +/- 0.08 as compared with control dogs (1.28 +/- 0.06, p less than 0.05) or dogs with compensated LV hypertrophy (1.23 +/- 0.08, p less than 0.05). During near-maximal coronary vasodilation with adenosine, all groups showed similar increases in subepimyocardial (epi) flow. While significant increases in subendomyocardial (endo) flow during adenosine infusion were seen in the control group (0.88 +/- 0.10 to 3.53 +/- 0.24 ml/min/g) and in dogs with compensated LV hypertrophy (1.12 +/- 0.14 to 3.60 +/- 0.16 ml/min/g), there was no change in endo flow in the LV failure dogs (1.55 +/- 0.20 to 1.71 +/- 0.47 ml/min/g) and a further significant reduction in the endo/epi flow ratio was observed (0.30 +/- 0.06, p less than 0.01). These hemodynamic changes were associated with chronic multifocal interstitial or discrete areas of fibrosis observed preferentially in endo layers. Thus, endo flow reserve is nearly exhausted in dogs with decompensated pressure overload LV hypertrophy, which may induced periodic episodes of endo ischemia resulting in myocyte necrosis and fibrosis, which in turn results in exacerbation of LV failure. .A Hittinger L; Shannon RP; Bishop SP; Gelpi RJ; Vatner SF. .I 200690 .U 90003669 .S Circ Res 9001; 65(4):981-8 .M Adult; Aged; Animal; Antibodies, Monoclonal/*IM; Blotting, Western; Cardiovascular Diseases/BL; Carrier Proteins/IM/*IP/ME; Enzyme-Linked Immunosorbent Assay; Fatty Acids/ME; Female; Human; Isoelectric Point; Male; Middle Age; Myocardium/*ME; Pulmonary Edema/BL; Rabbits; Rats; Reference Values; Support, U.S. Gov't, P.H.S.; Tissue Distribution. .T Rabbit heart fatty acid-binding protein. Isolation, characterization, and application of a monoclonal antibody. .P JOURNAL ARTICLE. .W A fatty acid-binding protein (FABP) was purified from rabbit heart and characterized with respect to size, isoelectric point, and tissue distribution. This protein was found in red muscle, diaphragm, and aorta, as well as in the heart. Amino acid composition of rabbit heart FABP differed only slightly from the human and rat proteins. Rabbit heart FABP was shown to bind two molecules of fatty acid. A monoclonal antibody was developed and used to demonstrate the feasibility of a one-step purification with affinity chromatography. Cross-reactivity was found between the human protein and the rabbit antibody, and an immunoassay was developed to human heart FABP. Levels of human heart FABP in the plasma of patients with acute myocardial infarction were significantly elevated (83 +/- 9 micrograms/ml) compared with patients with pulmonary edema (52 +/- 7 micrograms/ml) and normal volunteers (28 +/- 5 micrograms/ml; p less than 0.05, mean +/- SEM). .A Knowlton AA; Burrier RE; Brecher P. .I 200691 .U 90003670 .S Circ Res 9001; 65(4):989-96 .M Animal; Autoradiography; Calcium-Binding Proteins/BI; Chromatography, Thin Layer; Guinea Pigs; In Vitro; Inositol 1,4,5-Trisphosphate/ME; Isoproterenol/*PD; Myocardial Contraction/DE; Myocardium/*ME; Osmolar Concentration; Phosphoinositides/*ME; Phospholipids/BI; Phosphorus/ME; Stimulation, Chemical; Support, U.S. Gov't, P.H.S.; Time Factors; Troponin/BI. .T Changes in phosphoinositide turnover in isolated guinea pig hearts stimulated with isoproterenol. .P JOURNAL ARTICLE. .W The incorporation of 32Pi into phospholamban, troponin I, phosphatidylinositols, and inositol trisphosphates was studied in Langendorff-perfused guinea pig hearts stimulated with isoproterenol. Hearts were perfused with Krebs-Henseleit buffer containing [32P]Pk and freeze-clamped at different times during the positive inotropic response. Exposure of the hearts to 0.1 microM isoproterenol for up to 1 minute was associated with significant (up to threefold) increases in phospholamban and troponin I phosphorylation, but there was no significant increase in 32P incorporation into phospholipids. However, longer exposure (2 minutes or more) to isoproterenol was associated with increases in the degree of 32P labeling of phosphatidylinositols and phosphatidic acid. Examination of 32P labeling of inositol trisphosphates in the same hearts revealed that the radioactivity associated with these compounds decreased with time. The decreases were significant at times of exposure of 2 minutes or longer to beta-adrenergic stimulation. The tissue levels of the inositol 1,4,5-trisphosphate isoform were also measured in hearts perfused with isoproterenol for 3 minutes, and they were found to be significantly lower compared with values obtained in control hearts. The effects of isoproterenol on 32P incorporation into phospholipids and proteins were observed in the presence of prazosin, and they were completely abolished by the beta-receptor blocker propranolol. Examination of the phosphoinositide-specific phospholipase C activity in the perfused hearts revealed that isoproterenol stimulation was associated with a decrease in the membrane-associated enzymatic activity at physiological calcium concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) .A Edes I; Solaro RJ; Kranias EG. .I 200692 .U 90003671 .S Circ Res 9001; 65(4):997-1020 .M Animal; Biological Transport; Blood/*ME; Capillaries/CY/*ME; Capillary Permeability; Diffusion; Endothelium, Vascular/CY/*ME; Human; Models, Cardiovascular; Support, U.S. Gov't, P.H.S.. .T Blood-tissue exchange via transport and transformation by capillary endothelial cells. .P JOURNAL ARTICLE. .W The escape of solutes from the blood during passage along capillaries in heart and skeletal muscle occurs via diffusion through clefts between endothelial cells and, for some solutes, via adsorption to or transport across the luminal plasmalemma of the endothelial cell. To quantitate the rates of permeation via these two routes of transport across capillary wall, we have developed a linear model for transendothelial transport and illustrated its suitability for the design and analysis of multiple simultaneous indicator dilution curves from an organ. Data should be obtained for at least three solutes: 1) an intravascular reference, albumin; 2) a solute transported by endothelial cells; and 3) another reference solute, of the same molecular size as solute 2, which neither binds nor traverses cell membranes. The capillary-tissue convection-permeation model is spatially distributed and accounts for axial variation in concentrations, transport through and around endothelial cells, accumulation and consumption within them, exchange with the interstitium and parenchymal cells, and heterogeneity of regional flows. The upslope of the dilution curves is highly sensitive to unidirectional rate of loss at the luminal endothelial surface. There is less sensitivity to transport across the antiluminal surface, except when endothelial retention is low. The model is useful for receptor kinetics using tracers during steady-state conditions and allows distinction between equilibrium binding and reaction rate limitations. Uptake rates at the luminal surface are readily estimated by fitting the model to the experimental dilution curves. For adenosine and fatty acids, endothelial transport accounts for 30-99% of the transcapillary extraction. .A Bassingthwaighte JB; Wang CY; Chan IS. .I 200693 .U 90003672 .S Circulation 9001; 80(4):1003-9 .M Acid-Base Equilibrium; Acidosis/ME; Alkalosis, Respiratory/ME; Animal; Dogs; Electric Countershock/*; Electrocardiography; Electrophysiology; Energy Metabolism/*DE; Hydrogen/*ME; Hydrogen-Ion Concentration; Lidocaine/*PD; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T pH-dependent effects of lidocaine on defibrillation energy requirements in dogs. .P JOURNAL ARTICLE. .W Lidocaine increases the energy required for ventricular defibrillation in dogs. Because sodium channel-blocking agents that are weak bases have pH-dependent electrophysiologic effects, we investigated the pH dependence of lidocaine (pKa, 7.9) on internal defibrillation energy requirements in 28 dogs with atrial spring and left ventricular patch electrodes. Results of defibrillation testing were used to derive 50% and 90% successful energy requirements (ED50 and ED90) using logistic regression and were compared with analysis of variance. Acidosis produced by hydrochloric acid infusion decreased the arterial pH from 7.40 +/- 0.05 (SD) to 7.18 +/- 0.03 (n = 8, p less than 0.01), but no significant change in ED90 was observed (14 +/- 4 to 16 +/- 6 J). Lidocaine infusion to therapeutic levels (4.2 +/- .07 micrograms/ml) at normal pH (7.42 +/- 0.02) increased ED90 from 13 +/- 3 to 17 +/- 3 J (n = 6, p less than 0.05), and subsequent acidosis (pH 7.19 +/- 0.02, p less than 0.01) exacerbated this effect of lidocaine on ED90 (22 +/- 5 J, p less than 0.05). Alkalosis produced by respirator hyperventilation increased the arterial pH from 7.41 +/- 0.03 to 7.60 +/- 0.03 (n = 8, p less than 0.01), with a fall in ED90 from 13 +/- 4 to 8 +/- 3 J (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) .A Echt DS; Cato EL; Coxe DR. .I 200694 .U 90003673 .S Circulation 9001; 80(4):1010-5 .M Animal; Blood Pressure/DE; Consciousness; Dogs; Electrocardiography; Enkephalin, Leucine/AA/PD; Heart Failure, Congestive/*PP; Naloxone/AA/PD; Narcotic Antagonists/*PD; Oxymorphone/PD; Phenylephrine/PD; Pressoreceptors/*PP; Receptors, Endorphin/DE/*PH; Reflex/*PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Opiate receptor inhibition improves the blunted baroreflex function in conscious dogs with right-sided congestive heart failure. .P JOURNAL ARTICLE. .W The endogenous opiate system is activated in congestive heart failure. because endogenous opioids are known to depress the baroreflex function, we conducted studies to determine whether the increased endogenous opioids play a role in causing the reduced baroreflex function that occurs in heart failure. Right-sided congestive heart failure was produced in 16 dogs by tricuspid avulsion and progressive pulmonary artery constriction. Seven sham-operated dogs were included for comparison. Baroreflex function was measured in the conscious dogs after pretreatment with either normal saline or an opiate-receptor antagonist by bolus administration of phenylephrine. The slope of the regression line relating systolic blood pressure to cardiac cycle (R-R) interval was taken as an index of baroreflex sensitivity. Plasma beta-endorphin was elevated in the dogs with heart failure (15.3 +/- 2.5 pmol/l) compared with the sham-operated dogs (4.2 +/- 0.4 pmol/l, p less than 0.001). The dogs with heart failure also exhibited a reduced baroreflex sensitivity (3.84 +/- 0.19 msec/mm Hg) after saline pretreatment when compared with the sham-operated dogs (10.86 +/- 1.20 msec/mm Hg, p less than 0.001). Administration of naloxone hydrochloride increased the baroreflex sensitivity of dogs with heart failure to 5.16 +/- 0.26 msec/mm Hg (p less than 0.01) but produced no significant effects in sham-operated dogs (11.36 +/- 1.42 msec/mm Hg). To further study the site of action for the effect of naloxone, we measured baroreflex sensitivity in the dogs with heart failure after pretreatment with naloxonazine, a selective mu-receptor antagonist, with ICI 154,129, a selective delta-receptor antagonist, or with naloxone methobromide, a quaternary analogue of naloxone that does not penetrate the blood-brain barrier.(ABSTRACT TRUNCATED AT 250 WORDS) .A Sakamoto S; Liang CS. .I 200695 .U 90003674 .S Circulation 9001; 80(4):1016-28 .M Animal; Aorta/*PH; Balloon Dilatation/*/IS; Blood Pressure/*; Blood Volume/*; Myocardial Contraction; Reference Values; Sheep; Support, U.S. Gov't, P.H.S.; Systole. .T Measurement of end-systolic pressure-volume relations by intra-aortic balloon occlusion. .P JOURNAL ARTICLE. .W A new situ technique has been developed for measuring peak end-systolic elastance, Emax, that does not alter intrinsic or reflex-stimulated cardiac contractility. Afterload is varied by the inflation of an intra-aortic balloon catheter positioned in the ascending aorta. Balloon inflation is timed to interrupt ventricular ejection transiently at different times during the ejection phase, therefore, producing contraction at different ventricular volumes. Simultaneous measurement of left ventricular pressure and aortic flow during the occlusion sequence allows pressure versus ejected volume loops to be generated, from which the end-systolic pressure-volume relation is determined. End-systolic pressure-volume relation (ESPVR) was measured in six anesthetized Dorsett sheep with normal and enhanced contractile states. ESPVR was analyzed using both linear and nonlinear techniques. Although nonlinear components were seen in ESPVR, for the pressure-volume data range produced by the transient occlusions, linear approximations of ESPVR fit the end-systolic data points well. In the normal state, Emax, the slope of the linear ESPVR, was 1.01-5.08 mm Hg/ml in animals with body weights of 23-32 kg. After epinephrine infusion, Emax increased from 3.07 +/- 1.49 to 5.79 +/- 1.97 mm Hg/ml, which is consistent with previous investigations. Linear and nonlinear volume intercepts had a small increase with positive inotropic stimulation. Furthermore, serial measurements of Emax tracked cardiac function in depressed hearts with rapidly changing contractility. .A Gupta KB; Bavaria JE; Ratcliffe MB; Edmunds LH Jr; Bogen DK. .I 200696 .U 90003675 .S Circulation 9001; 80(4):1029-40 .M Angiography; Angioplasty, Transluminal/*AE/IS/MT; Animal; Arteriosclerosis/*TH; Atherosclerosis/*TH; Femoral Artery/*PA/RA; Hyperplasia; Male; Postoperative Complications; Rabbits; Support, U.S. Gov't, P.H.S.. .T Influence of inflation pressure and balloon size on the development of intimal hyperplasia after balloon angioplasty. A study in the atherosclerotic rabbit. .P JOURNAL ARTICLE. .W To evaluate the effect of balloon size and inflation pressure on acute and subsequent outcome following balloon angioplasty (BA), 70 New Zealand White rabbits with bilateral femoral atherosclerosis were assigned to four groups: group 1, oversized balloon, low inflation pressure (n = 35 vessels; balloon size, 3.0 mm/inflation pressure, 5 atm); group 2, oversized balloon, high inflation pressure (n = 36; 3.0 mm/10 atm); group 3, appropriate size, low inflation pressure (n = 17; 2.5 mm/5 atm); and group 4, appropriate size balloon, high inflation pressure (n = 19; 2.5 mm/10 atm). Angiograms were obtained before, 10 minutes after, and 28 days after BA and read by two blinded observers using electronic calipers. The in vivo balloon-to-vessel ratio was measured for each group. There were eight non-BA controls. Rabbits were sacrificed either immediately (n = 34) or at 28 days after BA (n = 36), with the femoral vessels pressure perfused for histologic and morphometric analysis. The latter was performed at 28 days only. Absolute angiographic diameters increased in all groups immediately after BA (p less than 0.01). Acute angiographic success, defined as greater than 20% increase in luminal diameter, was higher using high inflation pressure (group 2, 32/36 [89%] and group 4, 16/19 [84%] vs. group 1, 23/35 [66%] and group 3, 9/17 [53%]; p less than 0.05). A 3.0-mm balloon resulted in significant oversizing irrespective of inflation pressure (balloon-to-vessel ratio, 1.5 +/- 0.1 vs. 1.1 +/- 0.1 to 1, for the 2.5-mm balloon). Vessels exposed to high inflation pressure had a significantly higher incidence of mural thrombus, dissection (p less than 0.01), and medial necrosis versus low pressure (p less than 0.05). At 28 days, the rates of restenosis (defined as greater than 50% loss of initial gain) were 14/20 (70%), 11/16 (69%), 5/10 (50%), and 5/10 (50%) for groups 1 through 4 (p = NS; a trend in favor of the groups using an oversized balloon). There was an increase in the degree of intimal hyperplasia by morphometric analysis in all groups, being most marked in group 2 (oversized balloon and high inflation pressure, 1.7 +/- 0.9 vs. 0.5 +/- 0.2 mm for controls, p less than 0.001). We reached two conclusions. First, all protocols resulted in a significant increase in luminal diameter immediately after angioplasty with the highest success rate in vessels subjected to high pressure dilatation.(ABSTRACT TRUNCATED AT 400 WORDS) .A Sarembock IJ; LaVeau PJ; Sigal SL; Timms I; Sussman J; Haudenschild C; Ezekowitz MD. .I 200697 .U 90003676 .S Circulation 9001; 80(4):1041-8 .M Endothelium-Derived Relaxing Factor/*PH; Endothelium, Vascular/PH; Histamine/*PD; Human; Mammary Arteries/*DE/PH; Saphenous Vein/*DE/PH; Serotonin/*PD; Support, Non-U.S. Gov't; Thoracic Arteries; Vasoconstriction/*. .T Endothelium-derived relaxing factor and protection against contractions induced by histamine and serotonin in the human internal mammary artery and in the saphenous vein. .P JOURNAL ARTICLE. .W We investigated the release of endothelium-derived relaxing factor (EDRF) in response to serotonin and histamine in the human internal mammary artery and saphenous vein. The arteries and veins were obtained intraoperatively and were suspended in organ chambers to record isometric tension. In mammary arteries, histamine (10(-8) to 3 X 10(-6) M) induced relaxations in rings with (70 +/- 5%, IC50, 6.5 +/- 0.2) but not without endothelium (p less than 0.005 for rings with compared with those without endothelium, n = 7-10). The response was inhibited by methylene blue or hemoglobin, but not meclofenamate, and, therefore, EDRF was delineated as the mediator. Because chlorpheniramine but not cimetidine inhibited the response, EDRF was released by the H1-histaminergic receptor (n = 5-8). In contrast, in saphenous veins, histamine caused only weak or absent endothelium-dependent relaxations, but contractions were enhanced in rings with endothelium (p less than 0.05, n = 6). Serotonin did not induce endothelium-dependent relaxations, but contractions were markedly greater in veins compared with arteries (p less than 0.005, n = 6). The endothelium inhibited the maximal contraction to serotonin in arteries (p less than 0.034) but not in veins. Thus, EDRF protects against contractions induced by histamine and serotonin in the mammary artery but not in the saphenous vein. This may be important for improved graft function and patency of the artery compared with that of the vein. .A Yang ZH; Diederich D; Schneider K; Siebenmann R; Stulz P; von Segesser L; Turina M; Buhler FR; Luscher TF. .I 200698 .U 90003681 .S Circulation 9001; 80(4):1084-6 .M Blood Circulation/*/DE; Blood Vessels/PP; Cardiac Output; Cardiac Output, Low/DT/ME/*PP; Cardiovascular System/PP; Glycogen/ME; Human; Hydrogen/ME; Lactates/*ME; Muscles/BS; Nomenclature; Oxygen Consumption; Vasodilator Agents/TU. .T The peripheral circulation and lactic acid metabolism in heart, or cardiovascular, failure. .P JOURNAL ARTICLE. .A Wasserman K. .I 200699 .U 90003682 .S Circulation 9001; 80(4):1087-8 .M Aortic Valve/IN; Aortic Valve Stenosis/SU/*TH; Balloon Dilatation/*/AE/IS; Comparative Study; Evaluation Studies; Human; Infant, Newborn; Wounds, Penetrating/ET. .T Balloon therapy of critical aortic stenosis in the neonate. The therapeutic conundrum resolved? .P JOURNAL ARTICLE. .A Freedom RM. .I 200700 .U 90003683 .S Circulation 9001; 80(4):1089-90 .M Arteries/PP; Autonomic Nerve Block; Cold; Fingers/BS/IR; Human; Models, Cardiovascular; Raynaud's Disease/*PP; Receptors, Adrenergic, Alpha/PH; Vasoconstriction/*. .T The enigma of primary Raynaud's disease. .P JOURNAL ARTICLE. .A Coffman JD. .I 200701 .U 90003686 .S Circulation 9001; 80(4):1098 .M Electrocardiography, Ambulatory/*; Human; Telephone. .T Guidelines for ambulatory electrocardiography [letter] .P LETTER. .A David D. .I 200702 .U 90003687 .S Circulation 9001; 80(4):1098-100 .M Arrhythmia/DI; Electricity; Electrocardiography, Ambulatory/*/IS/ST; Human. .T ACC/AHA task force report: guidelines for ambulatory electrocardiography [letter] .P LETTER. .A Lohman JE. .I 200703 .U 90003689 .S Circulation 9001; 80(4):757-68 .M Adult; Atrioventricular Node/*; Biomechanics; Electric Stimulation Therapy/*MT; Electrophysiology; Follow-Up Studies; Heart Catheterization/*; Heart Conduction System/*; Human; Middle Age; Tachycardia, Atrioventricular Nodal Reentry/PP/*TH; Tachycardia, Supraventricular/*TH; Time Factors. .T Percutaneous catheter modification of the atrioventricular node. A potential cure for atrioventricular nodal reentrant tachycardia. .P JOURNAL ARTICLE. .W Our purpose was to describe a technique of atrioventricular (AV) node modification for patients with drug refractory AV nodal reentrant tachycardia (AVNRT). Nine patients (mean age, 45 +/- 20; range, 14-82) with recurrent drug refractory AVNRT (n = 8) or sudden cardiac death thought to be precipitated by AVNRT (n = 1) underwent a percutaneous catheter procedure to modify AV nodal function. The area between the electrode recording the maximal His-bundle electrogram and the ostium of the coronary sinus was divided into three zones. Perinodal direct current shocks of 100-300 J were delivered to one (n = 2), two (n = 3), or three (n = 4) zones without complications. The procedure endpoints were modification of AV conduction (either first degree AV block or complete retrograde ventriculo-atrial [VA] block) and failure to induce AVNRT before or after isoproterenol and/or atropine administration. Six of nine patients (67%) have had no inducible or spontaneous AVNRT over a mean follow-up of 12.3 +/- 4.1 months (range, 4.5-17). One of the six underwent repeat, successful modification, because AVNRT was inducible at restudy 2 days after the initial procedure. AVNRT recurred in three patients (33%), one early (3 days) and two late (3-4 months). Two of these patients underwent complete ablation of the AV junction and permanent pacemaker placement, whereas one is controlled with drug therapy. Therefore, AV nodal modification resulted in tachycardia control without antiarrhythmic drugs in six of nine (67%) and obviated the need for complete AV junctional ablation in seven of nine patients (78%). Elimination of AVNRT appears to result from either block in the retrograde fast pathway or modification of the antegrade slow pathway, such that AVNRT cannot be sustained. Additional findings suggest that an atrio-Hisian accessory connection may not be involved in AVNRT in some of these patients. Percutaneous catheter AV nodal modification appears to be a promising technique for treatment of refractory AVNRT and may obviate need for complete AV junctional ablation in a substantial number of patients with drug/pacemaker refractory AVNRT. .A Epstein LM; Scheinman MM; Langberg JJ; Chilson D; Goldberg HR; Griffin JC. .I 200704 .U 90003690 .S Circulation 9001; 80(4):769-81 .M Aged; Blood Pressure/*; Cardiac Output; Chronic Disease; Exercise/*; Female; Heart Failure, Congestive/ME/*PP; Hemodynamics/*; Human; Leg/BS; Male; Middle Age; Muscles/*BS; Regional Blood Flow; Respiration; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Relation between central and peripheral hemodynamics during exercise in patients with chronic heart failure. Muscle blood flow is reduced with maintenance of arterial perfusion pressure. .P JOURNAL ARTICLE. .W We studied the central hemodynamic, leg blood flow, and metabolic responses to maximal upright bicycle exercise in 30 patients with chronic heart failure attributable to severe left ventricular dysfunction (ejection fraction, 24 +/- 8%) and in 12 normal subjects. At peak exercise, patients demonstrated reduced oxygen consumption (15.1 +/- 4.8 vs. 32.1 +/- 9.9 ml/kg/min, p less than 0.001), cardiac output (8.7 +/- 3.2 vs. 18.6 +/- 4.4 l/min, p less than 0.001), and mean systemic arterial blood pressure (116 +/- 15 vs. 135 +/- 13 mm Hg, p less than 0.01) compared with normal subjects. Leg blood flow was decreased in patients versus normal subjects at rest and matched submaximal work rates and maximal exercise (2.1 +/- 1.9 vs. 6.4 +/- 1.4 l/min, all p less than 0.01). Mean systemic arterial blood pressure was no different in the two groups at rest or at matched submaximal work rates, whereas leg vascular resistance was higher in patients compared with normal subjects at rest, submaximal, and maximal exercise (all p less than 0.01). Although nonleg blood flow was decreased at rest in patients, it did not decrease significantly during exercise in either group. Peak exercise leg blood flow was related to peak exercise cardiac output in patients (r = 0.66, p less than 0.01) and normal subjects (r = 0.67, p less than 0.01). In patients, leg vascular resistance was not related to mean arterial blood pressure, pulmonary capillary wedge pressure, arterial catecholamines, arterial lactate, or femoral venous pH at rest or during exercise. Compared with normal subjects during submaximal exercise, patients demonstrated increased leg oxygen extraction and lactate production accompanied by decreased leg oxygen consumption. Thus, in patients with chronic heart failure compared with normal subjects, skeletal muscle perfusion is decreased at rest and during submaximal and maximal exercise, and local vascular resistance is increased. Our data indicate that nonleg blood flow and arterial blood pressure were preferentially maintained during exercise at the expense of leg hypoperfusion in our patients. This was associated with decreased leg oxygen utilization and increased leg oxygen extraction when compared to normal subjects, providing further evidence that reduced perfusion of skeletal muscle is important in causing early anaerobic skeletal muscle metabolism during exercise in subjects with this disorder.(ABSTRACT TRUNCATED AT 400 WORDS) .A Sullivan MJ; Knight JD; Higginbotham MB; Cobb FR. .I 200705 .U 90003691 .S Circulation 9001; 80(4):782-92 .M Adult; Aged; Echocardiography; Exercise; Female; Heart Catheterization/*; Heart Valve Prosthesis; Human; Male; Middle Age; Mitral Valve/PA/*SU; Mitral Valve Stenosis/DI/PP/*SU; Postoperative Complications; Reoperation; Veins. .T Indications, complications, and short-term clinical outcome of percutaneous transvenous mitral commissurotomy. .P JOURNAL ARTICLE. .W Percutaneous transvenous mitral commissurotomy was performed in 106 consecutive patients. Significant symptomatic improvement was achieved in 97 patients (92%). Mean left atrial pressure decreased (from 18 +/- 8 to 11 +/- 8 mm Hg, p less than 0.00001), mean mitral diastolic pressure gradient decreased (from 12 +/- 7 to 7 +/- 6 mm Hg, p less than 0.00001), and mitral valve area increased (from 1.40 +/- 0.40 to 2.00 +/- 0.50 cm2, p less than 0.00001). Based on echocardiographic characteristics of the mitral apparatus, patients were grouped retrospectively in three categories: pliable (group 1, n = 37), semipliable (group 2, n = 59), and rigid (group 3, n = 10). Clinical success was achieved in 36 patients of group 1 (97%) and in 55 patients of group 2 (93%). Only six patients in group 3 (60%) improved symptomatically (p less than 0.001 vs. group 1, p less than 0.001 vs. group 2). The severity of mitral regurgitation increased in five patients of group 1 (14%), in 12 of group 2 (20%), and in three of group 3 (33%). Six patients had recurrent symptoms at 9 months after commissurotomy. Recurrence of symptoms was significantly more frequent in group 3 compared with the other two groups (group 1, 3%; group 2, 4%; and group 3, 50%; p less than 0.0001 vs. groups 1 and 2). Multiple regression analysis identified the previously mentioned echocardiographic characteristics of the mitral apparatus as the significant predictor for clinical outcome. Thus, percutaneous transvenous mitral commissurotomy can be considered a safe and effective treatment for patients with pliable valves. Patients with semipliable or with rigid valves should be selected for operation very carefully. .A Nobuyoshi M; Hamasaki N; Kimura T; Nosaka H; Yokoi H; Yasumoto H; Horiuchi H; Nakashima H; Shindo T; Mori T; et al. .I 200706 .U 90003692 .S Circulation 9001; 80(4):793-806 .M Cardiac Pacing, Artificial/*/MT; Comparative Study; Computer Simulation/*; Electrophysiology; Forecasting; Human; Tachycardia, Supraventricular/PP/*TH. .T Programmed electrical stimulation at potential ventricular reentry circuit sites. Comparison of observations in humans with predictions from computer simulations. .P JOURNAL ARTICLE. .W The purpose of this study was to define specific types of resetting responses to programmed electrical stimulation during human ventricular tachycardia and to use computer simulations of reentry circuits to assess the possible mechanisms and pacing site location relative to the reentry circuit for each type of response. The effects of scanning single stimuli at 35 left ventricular endocardial sites during sustained monomorphic ventricular tachycardia in 12 patients were studied. In considering alterations in QRS configuration and the delay between the stimulus and the advanced QRS, we identified three types of resetting responses to scanning stimuli consistent with stimulation at sites in or near the reentry circuit at 12 abnormal endocardial sites in eight patients. Type 1: all capturing stimuli were followed after a delay by early QRS complexes that had the same configuration as the tachycardia complexes. Type 2: late stimuli reset tachycardia as in type 1 but early stimuli reset the tachycardia after altering the QRS configuration. Type 3: late stimuli reset tachycardia as in type 1, but early stimuli advanced tachycardia with a short stimulus to QRS delay without altering the QRS configuration. In the simulations, premature depolarization of sites in the circuit produced orthodromic and antidromic wavefronts. The orthodromic wavefront propagated through the circuit and exited the circuit at the same site as did the previous tachycardia wavefronts and advanced the tachycardia without altering the configuration of the advanced QRS. The antidromic wavefront of relatively late stimuli was confined within or near the circuit by collision with the orthodromic wavefront of the preceding tachycardia beat and failed to alter ventricular activation distant from the circuit. Therefore, the QRS configuration after the stimulus was unchanged. A type 1 response occurred when all capturing stimuli produced this effect. However, with increasing stimulus prematurity, the antidromic wavefront propagated farther before colliding with an orthodromic wavefront, and under some conditions, it exited the circuit from a site other than the original circuit "exit," and altered the ventricular activation sequence distant from the circuit and, therefore, the QRS configuration, producing a type 2 pattern. The type 3 pattern occurred when the antidromic wavefront of early premature beats captured the original circuit exit. The effect of a stimulus was dependent on the stimulus prematurity, the relative conduction times from the stimulation site to the potential sites of "exit" from the circuit, and the timing of the excitable gap at the stimulation site.(ABSTRACT TRUNCATED AT 400 WORDS) .A Stevenson WG; Nademanee K; Weiss JN; Wiener I; Baron K; Yeatman LA; Sherman CT. .I 200707 .U 90003693 .S Circulation 9001; 80(4):807-15 .M Angioplasty, Transluminal/*; Coronary Disease/PP/*TH; Dipyridamole/AD/*DU; Drug Administration Schedule; Echocardiography/*; Female; Follow-Up Studies; Hemodynamics; Human; Male; Middle Age; Postoperative Period; Preoperative Care. .T Usefulness of high-dose dipyridamole echocardiography test in coronary angioplasty. .P JOURNAL ARTICLE. .W Seventy-four consecutive patients with angina undergoing single-lesion percutaneous transluminal coronary angioplasty were evaluated with high-dose (up to 0.84 mg/kg during 10 minutes) dipyridamole echocardiography test (DET) before angioplasty and when possible, afterward. Angioplasty was clinically or angiographically successful in 63 patients and unsuccessful in 11. Before the procedure, 69 patients had a positive DET. Of these 69 patients, six with clinicall unsuccessful angioplasty had a dipyridamole time (i.e., the time from the onset of dipyridamole infusion to development of asynergy) lower than the 63 patients with clinically successfully angioplasty (4.2 +/- 2.9 vs. 7.0 +/- 2.9 minutes, mean +/- SD, p less than 0.01). In the five patients with angiographically unsuccessful angioplasty (residual stenosis diameter, greater than 50%), coronary stenosis decreased from 89 +/- 10 to 69 +/- 22 (p = NS); DET was positive in all five before and in four of the five after the procedure (100% vs. 80%, p = NS). In the 63 patients with angiographically successful angioplasty, coronary stenosis diameter was reduced from 85 +/- 9% to 30 +/- 10% (p less than 0.01). DET was positive in 58 patients before and in only 16 after the procedure (92% vs. 25%, p less than 0.01). In the 16 patients with positive DET, before and after angioplasty, dipyridamole time increased from 5.6 +/- 2.2 before to 7.3 +/- 2.4 minutes immediately after the procedure (p less than 0.05). After an average follow-up time of 10.8 +/- 5.9 months, angina recurred in eight of 47 patients with negative DET after angioplasty and in 11 of 16 patients with positive DET (17% vs. 69%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) .A Picano E; Pirelli S; Marzilli M; Faletra F; Lattanzi F; Campolo L; Massa D; Alberti A; Gara E; Distante A; et al. .I 200708 .U 90003694 .S Circulation 9001; 80(4):816-22 .M Adult; Aged; Exercise; Female; Heart/PP; Heart Enlargement/*ET/PA/PP; Heart Ventricle; Human; Male; Middle Age; Myocardial Infarction/*CO/DI; Myocardium/PA; Rest; Stroke Volume. .T Functional significance of hypertrophy of the noninfarcted myocardium after myocardial infarction in humans. .P JOURNAL ARTICLE. .W Hypertrophy of the noninfarcted left ventricle as a chronic response to myocardial infarction has been demonstrated in animals and at autopsy in humans. However, the functional significance of postmyocardial infarction hypertrophy is a subject of dispute. The purpose of this study was to determine the time course of development of postmyocardial infarction hypertrophy of the noninfarcted myocardium in humans and to assess its functional significance. Subcostal view, two-dimensional echocardiograms were recorded at rest and during peak exercise, 6 and 40 weeks postmyocardial infarction in 45 patients (16 anterior, 20 inferior, nine non-Q wave infarcts), for measurement of left ventricular mass and ejection fraction. The left ventricular mass index increased from 94 +/- 30 to 118 +/- 27 g/m2 (p less than 0.01) during the time of the two studies. There was a significant correlation between the change in left ventricular mass index and improved resting ejection fraction (r = 0.48, p less than 0.001) and exercise ejection fraction (r = 0.48, p less than 0.001) at the follow-up study. Of the 32 patients who increased their left ventricular mass index greater than 7%, 18 improved their rest ejection fraction greater than 0.05 units and 17 improved their exercise ejection fraction greater than 0.05 units. Conversely, of the 13 patients who failed to increase their left ventricular mass index, only three improved their rest ejection fraction and one improved the exercise ejection fraction (Fisher's exact test, p less than 0.05). We reached three conclusions. First, in humans, significant hypertrophy of the noninfarcted myocardium can be detected by two-dimensional echocardiography, 9 months postmyocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS) .A Ginzton LE; Conant R; Rodrigues DM; Laks MM. .I 200709 .U 90003695 .S Circulation 9001; 80(4):823-30 .M Adult; Aged; Chronic Disease; Diastole; Echocardiography; Echocardiography, Doppler; Endarterectomy/*; Female; Heart/*PP; Heart Catheterization; Heart Ventricle; Human; Hypertension, Pulmonary/ET/*SU; Male; Middle Age; Postoperative Period; Pulmonary Embolism/CO/PP/*SU. .T Early improvement in left ventricular diastolic function after relief of chronic right ventricular pressure overload. .P JOURNAL ARTICLE. .W Chronic right ventricular pressure overload is associated with left ventricular diastolic dysfunction. Whether or not an abrupt reduction in pulmonary artery pressure in patients with chronic pulmonary hypertension results in early improvement of left ventricular diastolic function is unknown. To assess this, the Doppler indexes of left ventricular diastolic function and echocardiographic measures of left ventricular volume were analyzed in 22 patients (age, 41 +/- 14 years, mean +/- SD) before and within 1 week after pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension. Mean duration of cardiopulmonary symptoms was 37 months (range, 4 months to 9 years). After operation, mean pulmonary artery pressure and pulmonary vascular resistance decreased (50 +/- 13 to 29 +/- 9 mm Hg and 904 +/- 654 to 283 +/- 243 dynes.sec/cm5, respectively, both p less than 0.001), pulmonary artery wedge pressure was unchanged (11 +/- 5 to 12 +/- 5 mm Hg), and cardiac index increased (2.0 +/- 0.5 to 2.8 +/- 0.7 l/min/m2 p less than 0.001). Left ventricular end-diastolic volume and stroke volume increased significantly (58.5 +/- 18.0 to 76.6 +/- 25.0 ml and 30.3 +/- 12.3 to 41.8 +/- 12.5 ml, respectively, both p less than 0.001) after surgery.(ABSTRACT TRUNCATED AT 250 WORDS) .A Dittrich HC; Chow LC; Nicod PH. .I 200710 .U 90003696 .S Circulation 9001; 80(4):831-9 .M Aortic Valve/RA/*SU; Aortic Valve Stenosis/RA/SU/*TH; Aortography; Balloon Dilatation/*; Comparative Study; Evaluation Studies; Human; Infant, Newborn; Postoperative Complications/MO; Reoperation. .T Neonatal critical valvar aortic stenosis. A comparison of surgical and balloon dilation therapy. .P JOURNAL ARTICLE. .W Balloon aortic valvotomy (BAV) is an alternative to surgical valvotomy in infants and children. We compared BAV in 16 consecutive neonates (1985-1988) to surgical valvotomy in a prior group of 16 consecutive neonates (1978-1984). Both groups were comparable in terms of age, weight, hemodynamic data, left ventricular size, and associated lesions. There were six early and one late deaths after surgery. Five out of six neonates requiring a second operation died. Left ventricular size (measured in 13 neonates) had some influence on survival after surgery: three of three with small or hypoplastic left ventricles and three of 10 with normal-sized left ventricles died. After BAV, there were three early deaths, two patients who underwent stage I palliation of hypoplastic left heart syndrome, and two late deaths. As with surgical valvotomy, left ventricular size seemed to influence survival after BAV: five of six with small or hypoplastic left ventricles died or underwent stage I palliation for hypoplastic left heart syndrome and two of nine with normal-sized left ventricles died. At follow-up (26 +/- 17 months) in six patients in the surgical group, the peak systolic ejection gradient (PSEG) was 52.2 +/- 23 mm Hg and left ventricular end-diastolic pressure (LVEDP) 18.2 +/- 5.2 mm Hg. Aortic regurgitation was mild in five and moderate in the sixth patient. At follow-up (17.6 +/- 7.8 months) in nine patients in the balloon dilation group, the PSEG was 45.6 +/- 11 mm Hg in five patients at catheterization and 43.8 +/- 22.9 mm Hg in four patients by echocardiography-Doppler. Aortic regurgitation was mild in three and absent in the other six patients.(ABSTRACT TRUNCATED AT 250 WORDS) .A Zeevi B; Keane JF; Castaneda AR; Perry SB; Lock JE. .I 200711 .U 90003697 .S Circulation 9001; 80(4):840-5 .M Adult; Aortic Coarctation/MO/PP/*SU; Blood Pressure; Cardiovascular Diseases/SU; Female; Follow-Up Studies; Human; Male; Postoperative Complications; Prognosis; Reoperation; Time Factors. .T Coarctation of the aorta. Long-term follow-up and prediction of outcome after surgical correction [see comments] .P JOURNAL ARTICLE. .W The long-term clinical course was studied in 646 patients, who underwent isolated operative repair of coarctation of the aorta at the Mayo Clinic from 1946 to 1981. There were 17 perioperative deaths, and 58 patients were lost to follow-up. Of the 571 patients with long-term follow-up, 11% required subsequent cardiovascular surgery, and 25% developed hypertension. There were 87 late deaths. The mean age at death was 38 years (range, 0-67 years). Estimated survival analysis revealed 91% of patients alive at 10, 84% at 20, and 72% at 30 years after operative repair. The most common cause of late death was coronary artery disease in 32 patients, followed by sudden death, heart failure, cerebrovascular accidents, and ruptured aortic aneurysm. Age, sex, and postoperative systolic blood pressure were found to be independently predictive of survival. For patients less than 14 years of age at the time of initial coarctectomy, survival to 20 years was 91%, and for patients 14 years or older at the time of operation, survival was 79%. The best survivorship was observed in patients operated on at 9 years of age or less. The higher the postoperative systolic pressure, the higher the probability of death. This study has the largest population undergoing repair of coarctation of the aorta with a median follow-up of as long as 20 years. Four main points emerged. 1) Age at the time of initial repair is the most important predictor of long-term survival. Surgery should be offered to patients after age 1 year or sooner if hypertension is severe. 2) Coronary artery disease is the most common cause of late death.(ABSTRACT TRUNCATED AT 250 WORDS) .A Cohen M; Fuster V; Steele PM; Driscoll D; McGoon DC. .I 200712 .U 90003698 .S Circulation 9001; 80(4):846-52 .M Accident Prevention/*; Adult; Aged; Aged, 80 and over; Case Report; Exercise Test/*AE/MT; Female; Human; Male; Middle Age; Myocardial Infarction/ET; Safety/*; Ventricular Fibrillation/ET. .T The safety of maximal exercise testing [see comments] .P JOURNAL ARTICLE. .W Previous reports on the safety of exercise testing have been based on surveys from different testing facilities with a variety of testing protocols and patient types. From 1971 through 1987, 71,914 maximal exercise tests conducted in a population with a low prevalence of known coronary heart disease under uniform conditions at a single medical facility resulted in six major cardiac complications including one death. No complications have occurred in the past 10 years in 45,000 maximal tests. The overall cardiac complication rate in men and women is 0.8 complications per 10,000 tests with 95% confidence intervals of 0.3-1.9 complications per 10,000 tests. Maximal exercise testing appears safer than some previously published reports have suggested and seems to be getting safer with time. .A Gibbons L; Blair SN; Kohl HW; Cooper K. .I 200713 .U 90003699 .S Circulation 9001; 80(4):853-8 .M Adrenergic Beta Receptor Blockaders/*TU; Aged; Circadian Rhythm/*; Coronary Disease/CO/DT/PP; Female; Human; Male; Middle Age; Myocardial Infarction/*ET/PP; Prospective Studies; Streptokinase/TU. .T Increased morning incidence of myocardial infarction in the ISAM Study: absence with prior beta-adrenergic blockade. ISAM Study Group. .P JOURNAL ARTICLE. .W The time of acute myocardial infarction was determined in all 1,741 patients of the ISAM (Intravenous Streptokinase in Acute Myocardial Infarction) Study, based on onset of clinical symptoms and evaluation of plasma CK-MB enzyme time-activity curves. The incidence of myocardial infarction was markedly increased between 6:00 AM and 12:00 noon compared with other times of day (p less than 0.001). Myocardial infarction occurred 3.8 times more frequently between 8:00 and 9:00 AM (hour of maximum incidence) than between 12:00 midnight and 1:00 AM (hour of minimum incidence). Time of myocardial infarction based on clinical and enzymatic methods correlated well (r = 0.95). Patients with higher or lower left ventricular ejection fraction, higher or lower degree of wall motion abnormalities and residual stenosis of the coronary arteries, and one-, two-, or three-vessel disease exhibited a similar circadian pattern, suggesting that the morning is a risk period for patients with mild as well as severe coronary artery disease. Only the group of patients receiving beta-adrenergic blocking therapy before the event did not show an increased morning incidence of myocardial infarction. This observation may contribute to an understanding of the mechanisms by which beta-blockers reduce the incidence of myocardial infarction. Further investigation of physiologic changes occurring during the morning period of increased risk of myocardial infarction may lead to better understanding of the disorder. Design and timing of cardioprotective medication may play a crucial role in improving prevention of acute myocardial infarction. .A Willich SN; Linderer T; Wegscheider K; Leizorovicz A; Alamercery I; Schroder R. .I 200714 .U 90003700 .S Circulation 9001; 80(4):859-62 .M Cold; Comparative Study; Fingers/*BS/IR; Human; Nerve Block/*; Raynaud's Disease/*PP; Regional Blood Flow; Scleroderma, Systemic/PP; Support, U.S. Gov't, P.H.S.; Vasoconstriction/*. .T Induction of vasospastic attacks despite digital nerve block in Raynaud's disease and phenomenon. .P JOURNAL ARTICLE. .W Using a combination of environmental and local cooling, we induced vasospastic attacks of Raynaud's phenomenon in nine of 11 patients with idiopathic Raynaud's disease and in eight of 10 patients with scleroderma. Attacks were defined as occurring if two of the possible three color changes (pallor, cyanosis, and rubor) occurred, and serial photographs were scored by three independent raters. Two fingers on one hand were anesthetized by local injection of lidocaine, and the effectiveness of nerve blocks was verified by plethysmography. The frequency of vasospastic attacks in nerve-blocked fingers was not significantly different from that in the corresponding intact fingers on the contralateral hand. These findings show that the vasospastic attacks of Raynaud's disease and phenomenon can occur without the involvement of efferent digital nerves and argue against the etiologic role of sympathetic hyperactivity. .A Freedman RR; Mayes MD; Sabharwal SC. .I 200715 .U 90003701 .S Circulation 9001; 80(4):863-72 .M Acetates/*DU; Adolescence; Adult; Blood Pressure; Carbon Radioisotopes/DU; Heart/RI; Heart Rate; Hemodynamics; Human; Male; Myocardium/*ME; Oxygen Consumption/*; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Tomography, Emission-Computed/*. .T Regional myocardial oxygen consumption determined noninvasively in humans with [1-11C]acetate and dynamic positron tomography. .P JOURNAL ARTICLE. .W Experimental studies of animals have previously demonstrated the validity of [1-11C]acetate as a tracer of oxidative metabolism for use with positron emission tomography. The present study was undertaken to define in normal human volunteers the relation between myocardial clearance kinetics of [1-11C]acetate, and the rate-pressure product as an index of myocardial oxygen consumption. Twenty-two studies were performed of 12 volunteers. The rate-pressure product was increased with continuous supine bicycle exercise in six studies. Of the 16 resting studies, seven were performed in the fasted state and nine following an oral glucose load, to define possible effects of substrate availability on the tracer-tissue kinetics. Myocardial tissue time-activity curves were biexponential. Clearance of activity was homogeneous throughout the myocardium. The rate constants k1, obtained from biexponential fitting, and kmono, obtained by monoexponential fitting of the initial linear portion of the time-activity curves, correlated well with the rate-pressure product. Although the correlation coefficient was higher for k1 than for kmono (0.95 vs. 0.91), analysis on a sectorial basis showed less regional variability in kmono. This suggests that kmono, which is more practical than k1 because it requires shorter acquisition times, may be more clinically and experimentally useful for detection of myocardial segments with abnormal oxygen consumption. Overall, changes in myocardial substrate supply were without significant effect on the relation between the rate constants (k1 and kmono) and the rate-pressure product, although a small decrease in kmono/rate-pressure product was observed following oral glucose by paired analysis in four subjects. It is concluded that [1-11C]acetate can be used for the noninvasive measurement of myocardial oxygen consumption in humans with positron emission tomography, and, thus, has clinical and experimental potential as a tool for the understanding and diagnosis of myocardial disease. .A Armbrecht JJ; Buxton DB; Brunken RC; Phelps ME; Schelbert HR. .I 200716 .U 90003706 .S Circulation 9001; 80(4):915-24 .M Comparative Study; Echocardiography; Heart Sounds; Human; Marfan Syndrome/CO/*DI; Mitral Valve/*PA/PP; Mitral Valve Prolapse/CO/*PA/PP; Movement/*; Reference Values. .T Mitral valve dimensions and motion in Marfan patients with and without mitral valve prolapse. Comparison to primary mitral valve prolapse and normal subjects. .P JOURNAL ARTICLE. .W To determine mitral valve and extravalvular findings associated with mitral valve prolapse (MVP) in patients with the Marfan syndrome, we compared mitral leaflet and anular dimensions and motion by computerized two-dimensional echocardiography in 53 Marfan patients (28 with M-mode echocardiographic MVP) to those in 48 adults with primary MVP and in 35 normal subjects. Mitral leaflet billowing occurred in 28 of 28 Marfan patients with M-mode MVP versus 24 of 48 with primary MVP (p less than 0.00005), 0 of 25 Marfan patients without M-mode MVP, and 0 of 35 normal subjects (both, p less than 0.0001). Billowing occurred on the first systolic frame in 8 of 28 Marfan-MVP patients, in whom posterior leaflet chordae arose abnormally from the posterior ventricular wall, and in no other subjects. These patients had large mitral valves and normal anular dynamics, whereas the remaining 20 Marfan-MVP patients had increased systolic anular expansion. Marfan-MVP patients were younger than those without MVP (29 +/- 12 vs. 38 +/- 15 years, p less than 0.02) and had lower body mass index (19.8 +/- 2.7 vs. 23.9 +/- 2.9 kg/m2, p less than 0.00005) and systolic blood pressure (120 +/- 20 vs. 133 +/- 20 mm Hg, p less than 0.05), similar to differences between primary MVP and normal subjects in body mass index (21.5 +/- 3.0 vs. 23.9 +/- 4.8 kg/m2, p less than 0.01) and systolic pressure (118 +/- 14 vs. 125 +/- 18 mm Hg, p less than 0.05). Marfan patients with and without MVP had similar arm span, arm span to height ratio, upper to lower segment ratio, and prevalence of ectopia lentis and thoracic bony abnormalities, but arachnodactyly was more frequent in those with MVP (82% and 48%, respectively; p less than 0.02). We conclude that 1) leaflet billowing occurs more uniformly in Marfan patients with MVP than in primary MVP, 2) MVP in Marfan patients may be due to either valve enlargement with distinctively abnormal chordal architecture or abnormal mitral anular distensibility, 3) Marfan patients with MVP have low body weight and systolic blood pressure, similar to primary MVP, and 4) Marfan patients with MVP more commonly have arachnodactyly but otherwise have similar skeletal and anthropometric characteristics to other Marfan patients. .A Pini R; Roman MJ; Kramer-Fox R; Devereux RB. .I 200717 .U 90003709 .S Circulation 9001; 80(4):941-50 .M Animal; Blood Circulation/*; Blood Pressure/*; Comparative Study; Constriction, Pathologic; Coronary Disease/*PP; Diastole; Dogs; Female; Hyperemia/*PP; Male; Regression Analysis; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T The diastolic hyperemic flow versus pressure relation. A new index of coronary stenosis severity and flow reserve. .P JOURNAL ARTICLE. .W The measurement of coronary flow reserve, traditionally calculated as the ratio of maximal hyperemic blood flow divided by basal flow, is difficult to interpret in serial studies because fluctuating hemodynamic parameters may affect either basal or hyperemic flow measurements. To determine the magnitude of this problem and to develop alternative approaches for measuring vascular reserve, 10 anesthetized dogs were instrumented with aortic and inferior vena cava occluders, electromagnetic coronary flow probes, and high-fidelity micromanometers in the left ventricle and aortic root. Coronary flow was measured in the basal state and during maximal hyperemia induced by a steady-state adenosine infusion. Observations were made in the absence of a stenosis and in the presence of two incremental degrees of subcritical stenosis produced by a rigid, external screw occluder. Several parameters of vascular reserve were determined: 1) coronary flow reserve (defined above), 2) mean hyperemic flow divided by mean aortic pressure, 3) mean hyperemic flow divided by the difference between mean aortic pressure and left ventricular end-diastolic pressure, and 4) the slope of the instantaneous relation between diastolic hyperemic flow versus pressure. Each parameter was measured during five steady-state pressure levels achieved by partial occlusion of either the inferior vena cava or the aorta and the levels ranged from 82 +/- 8 mm Hg (mean +/- SD) to 127 +/- 9 mm Hg during hyperemia. All measures of vascular reserve were found to be dependent on hemodynamic parameters such as heart rate and mean aortic pressure. The slope of the instantaneous relation between diastolic hyperemic flow and pressure, however, showed only minimal dependence on heart rate and, in contrast to coronary flow reserve measurements, distinguished between the normal and the two stenotic states. Further, this optimal performance of the hyperemic flow versus pressure slope index was shown in a model in which coronary flow and myocardial work were not independently controlled. This index provides a sensitive and reliable indication of subcritical stenosis severity that may have clinical applications. .A Mancini GB; McGillem MJ; DeBoe SF; Gallagher KP. .I 200718 .U 90003710 .S Circulation 9001; 80(4):951-61 .M Animal; Chronic Disease; Dogs; Electrocardiography; Female; Follow-Up Studies; Heart Block/*ET/PA/PP; Heart Catheterization/*; Heart Conduction System/PA; Male; Myocardium/PA; Radiation Injuries, Experimental/*; Radio Waves/*; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Time Factors. .T Chronic incomplete atrioventricular block induced by radiofrequency catheter ablation. .P JOURNAL ARTICLE. .W To determine if catheter ablation of the atrioventricular (AV) junction with radiofrequency energy can induce chronic incomplete (first- and second-degree) AV block to avoid the need for a permanent pacemaker, 20 closed-chest dogs were studied. Group 1 (10 dogs) received radiofrequency energy (750 kHz) with a fixed power setting (5 or 10 W) while increasing the pulse duration from 10 to 50 seconds for each application. Group 2 (10 dogs) received energy with a fixed pulse duration (20 or 30 seconds) while increasing the power setting from 5 to 10 W or from 10 to 20 W during each energy delivery. Radiofrequency energy was delivered between a chest-patch electrode and the distal electrode of a regular 7F tripolar His bundle catheter. For each application, the energy delivery was interrupted when 1) the PR interval prolonged (greater than 50%) or 2) second-degree or complete AV block occurred and persisted up to 5 seconds. The ablation procedure ended when there was 1) persistent PR prolongation (greater than 50%) or persistent second-degree AV block (lasting greater than 30 minutes) after ablation, 2) occurrence of two consecutive transient (less than 1 minute) complete AV blocks after each energy delivery, or 3) complete AV block (lasting greater than 2 minutes) after ablation. Of seven dogs in group 1 and five dogs in group 2 in which incomplete AV block was achieved 1 hour after the procedure, six in group 1 and five in group 2 remained in incomplete AV block 2-3 months after ablation. One dog in group 1 progressed into complete AV block. Of the remaining three dogs in group 1 and five dogs in group 2 in which complete AV block was initially achieved 1 hour after ablation, two in group 1 and four in group 2 continued to have complete AV block, whereas one in each group had AV conduction returned to incomplete at 1-2 months of follow-up. Thus, a total of 13 dogs had chronic incomplete AV block induced by radiofrequency catheter ablation. Pathologic examination of the conduction system in two dogs with first-degree AV block, two dogs with second-degree AV block, and one dog with complete AV block showed discrete scars involving the approaches to the AV node and the AV node itself. It is concluded that, in most dogs studied, chronic incomplete AV block could be achieved by careful titration of the dosage of radiofrequency energy and by regulation of the ablation end points. .A Huang SK; Bharati S; Graham AR; Gorman G; Lev M. .I 200719 .U 90003711 .S Circulation 9001; 80(4):962-8 .M Animal; Dogs; Endocardium/PA/*RE; Radio Waves/*; Support, Non-U.S. Gov't; Technology, Radiologic/*; Time Factors. .T Control of radiofrequency lesion size by power regulation. .P JOURNAL ARTICLE. .W The influence of power and exposure duration on lesion size in radiofrequency catheter ablation was investigated in 15 closed-chest dogs. Radiofrequency energy was delivered to the right ventricular endocardium between the tip of a standard 6F electrode catheter and a large W and durations of 5, 10, 20, 30, and 60 seconds. At necropsy 1 week later, well-demarcated homogeneous lesions were found when power had exceeded a threshold level that decreased from 1.8 W at 5 seconds to 0.7 W at 60 seconds. Lesion size ranged from 0 to 7.5 mm in depth and 0 to 9 mm in diameter. For the 5, 10, and 20 second ablations, lesion size was determined by exposure duration and power level. However, after a 20 second exposure, lesion size had reached maturity and was related to delivered power only. Therefore, a gradual, controlled growth of the lesion can be obtained by a stepwise increase of the radiofrequency power level with ample exposure duration at each level to allow for stabilization. At levels exceeding 7 W, the formation of a thin insulating layer of blood coagulum on the electrode surface caused an abrupt increase of impedance within approximately 30 seconds. Therefore, lesion size is limited to 8.5 mm in radiofrequency ablation with a standard 6F endocardial electrode catheter. .A Wittkampf FH; Hauer RN; Robles de Medina EO. .I 200720 .U 90003712 .S Circulation 9001; 80(4):969-82 .M Albumins/DU; Animal; Coronary Disease/*DI; DTPA; Gadolinium; Histocytochemistry; Magnetic Resonance Imaging/*; Myocardial Reperfusion Injury/*DI/PA; Myocardium/*PA; Nuclear Magnetic Resonance/*DU; Organometallic Compounds; Rats; Support, U.S. Gov't, P.H.S.. .T Assessment of myocardial salvage after ischemia and reperfusion using magnetic resonance imaging and spectroscopy. .P JOURNAL ARTICLE. .W To test the hypothesis that contrast-enhanced magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) can differentiate reversible from irreversible myocardial injury, these modalities were used to study ischemia and reperfusion in a rat model. The presence of ischemia and reperfusion were confirmed with radiolabeled microspheres (n = 6). Groups of animals were subjected to either 16 (n = 17), 30 (n = 14), 60 (n = 11), or 90 (n = 14) minutes of left coronary artery (LCA) occlusion and 60 minutes reperfusion. After albumin-gadolinium (Gd)-DTPA injection, contrast-enhanced, T1-weighted, spin-echo proton images were acquired at baseline and every 16 minutes during LCA occlusion and reperfusion. In separate experiments, 31phosphorus (31P) spectra were acquired at similar time points during ischemia and reperfusion. After 16 minutes occlusion, normally perfused myocardium enhanced significantly compared with ischemic myocardium on MRI (104 +/- 7.9% vs. 61 +/- 11.0%, p less than 0.05, n = 5, mean +/- SEM, % of baseline value). MRS showed reduced phosphocreatine (PCr) and adenosine triphosphate (ATP) (58.8 +/- 2.4%, p less than or equal to 0.01; 81.4 +/- 2.4, p less than or equal to 0.01, n = 12). After 16 or 30 minutes ischemia, reflow resulted in uniform MRI signal intensity of the ischemic zone compared with normal myocardium (93.5 +/- 11.3 vs. 80.9 +/- 7.0, p = NS, n = 11, % of baseline value at 30 minutes reperfusion) and PCr recovery on MRS (94.3 +/- 4.0%, p = NS, n = 20, % baseline value at 30 minutes reflow). After 60 and 90 minutes ischemia, reflow resulted in marked enhancement of reperfused compared with normal myocardium on MRI (254.0 +/- 30.0 vs. 78.3 +/- 9.2, p less than or equal to 0.01, n = 10) and no recovery of PCr on MRS (64.1 +/- 3.0, p = NS, n = 14). Triphenyltetrazolium chloride (TTC) staining revealed transmural myocardial infarction (MI) in all hearts subjected to 60 or 90 minutes ischemia and reflow, and small nontransmural MIs in only 2/11 hearts subjected to 16 or 30 minutes ischemia and reperfusion. Thus, 1) MRI with albumin-Gd-DTPA is useful for identifying myocardial ischemia by enhancing the contrast between normally perfused and ischemic myocardia; 2) MRI with albumin-Gd-DTPA is useful for identifying reperfusion after myocardial ischemia; and 3) after reperfusion, reversible can be distinguished from irreversible myocardial injury by characteristic findings on MRI and MRS. .A Wolfe CL; Moseley ME; Wikstrom MG; Sievers RE; Wendland MF; Dupon JW; Finkbeiner WE; Lipton MJ; Parmley WW; Brasch RC. .I 200721 .U 90003713 .S Circulation 9001; 80(4):983-93 .M Animal; Benzazepines/PD/*TU; Biomechanics; Cardiovascular Agents/TU; Coronary Circulation; Coronary Disease/*DT/PP; Depression, Chemical; Heart/PP; Heart Rate/*DE; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Swine. .T Mechanisms of improved ischemic regional dysfunction by bradycardia. Studies on UL-FS 49 in swine. .P JOURNAL ARTICLE. .W In anesthetized swine, the left anterior descending coronary artery was cannulated and perfused at constant blood flow levels during two grades of ischemia. In one group (n = 10), moderate ischemia reduced percent systolic wall thickening (by sonomicrometry) from 25 +/- 7% to 6 +/- 2%, whereas in the other group (n = 7), severe ischemia reduced percent wall thickening from 24 +/- 6% to -0.5 +/- 4%. Heart rate was paced in both groups at 91 beats/min. After reperfusion and complete return to control conditions, administration of the bradycardic agent UL-FS 49 (0.37 mg/kg i.v.) decreased the heart rate to 55 +/- 5 beats/min. During subsequent ischemia at the same coronary inflow as before bradycardia, percent wall thickening in the ischemic zone during moderate ischemia was increased from 6 +/- 2% to 25 +/- 6% (p less than 0.01) (not significantly different from control without ischemia), and during severe ischemia, percent wall thickening increased from -0.5 +/- 4% to 13 +/- 7% (p less than 0.01). During moderate ischemia, bradycardia caused an increase in the subendocardial blood flow from 0.24 +/- 0.60 to 0.42 +/- 0.17 (ml/min)/g (p less than 0.009) and during severe ischemia, bradycardia caused an increase from 0.14 +/- 0.08 to 0.2 +/- 0.1 (ml/min)/g (p less than 0.001). At each level of ischemia, a more marked improvement occurred in subendocardial blood flow per beat ([(ml/min)/g]/heart rate). The relation between myocardial blood flow and wall function at a heart rate of 55 beats/min (n = 14) was plotted and compared with that studied at a heart rate of 122 beats/min in another group of pigs (n = 14). The increase in subendocardial blood flow per minute during bradycardia was not sufficient to explain the striking increase in function; thus, an independent relation (p less than 0.05) between blood flow per minute and contractile function (percent wall thickening) was found for for each heart rate. In contrast, when myocardial blood flow was normalized for heart rate and expressed per beat, data from both heart rate groups could be described by a single relation. Thus, the subendocardial blood flow per beat predicted wall function independently of heart rate and accounted for changes in both oxygen supply and demand. .A Indolfi C; Guth BD; Miura T; Miyazaki S; Schulz R; Ross J Jr. .I 200722 .U 90003714 .S Circulation 9001; 80(4):994-1002 .M Alkalosis, Respiratory/PP; Anilides/*PD; Animal; Bicarbonates/PD; Dogs; Electroencephalography; Electrophysiology; Female; Heart/*DE/PH/PP; Heart Conduction System/DE; Heart Rate; Hyperventilation/PP; Male; Sodium/*PD; Sodium Chloride/PD; Support, U.S. Gov't, P.H.S.; Time Factors. .T Acute electrophysiologic effects of sodium administration in dogs treated with O-desmethyl encainide. .P JOURNAL ARTICLE. .W Conduction slowing is the major in vivo effect of sodium channel blocking drugs. Although this action may promote arrhythmia suppression, apparently paradoxical arrhythmia aggravation does occur. The latter outcome is most frequently seen during treatment with the class IC agents such as encainide or flecainide, which are potent depressors of conduction even at usual plasma concentrations and heart rates. Anecdotal reports in patients with such drug toxicity have suggested a beneficial effect of sodium lactate or NaHCO3 administration. The purpose of this study, therefore, was to examine the changes induced by sodium loading on the electrophysiologic properties of the canine ventricle pretreated with a class IC drug. Thirty dogs received loading and maintenance infusions of O-desmethyl encainide (ODE), an encainide metabolite that as a sodium channel blocker is approximately 10 times more potent than the parent drug. Interventions were administered during the maintenance phase when stable plasma ODE concentrations of 448 +/- 68 (SEM) ng/ml were present, and QRS was prolonged from 62 +/- 1 to 89 +/- 2 msec, and HV was prolonged from 28 +/- 1 to 50 +/- 1 msec. NaHCO3 (5 meq/kg during 1 minute) shortened QRS from 92 +/- 6 to 76 +/- 3 msec and shortened HV from 44 +/- 3 to 37 +/- 3 msec within 10 minutes (both p less than 0.01). NaHCO3 also significantly prolonged endocardial monophasic action potential duration from 231 +/- 22 to 272 +/- 33 msec and decreased serum [K+] from 3.8 +/- 0.2 to 3.0 +/- 0.2 meq/l, but it did not alter plasma ODE concentration.(ABSTRACT TRUNCATED AT 250 WORDS) .A Bajaj AK; Woosley RL; Roden DM. .I 200723 .U 90003715 .S Circulation 9001; 80(4 Pt 2):II1-II808 .M Animal; Cardiovascular Diseases/*; Cardiovascular System/*PH; Heart/*PH; Heart Diseases/*; Human. .T Abstracts from the 62nd scientific sessions: American Heart Association. New Orleans, Louisiana, November 13-16, 1989. .P JOURNAL ARTICLE. .I 200724 .U 90003954 .S Clin Nephrol 9001; 32(3):101-6 .M Adolescence; Autoantibodies/*AN; Case Report; Cytoplasm/*IM; Female; Hemorrhage/*IM; Human; IgM/*AN; Lung Diseases/*IM; Male; Middle Age; Neutrophils/*IM; Support, Non-U.S. Gov't; Vasculitis/*IM. .T Severe pulmonary hemorrhage and systemic vasculitis in association with circulating anti-neutrophil cytoplasm antibodies of IgM class only. .P JOURNAL ARTICLE. .W We report an association of severe pulmonary hemorrhage with circulating autoantibodies to neutrophil cytoplasmic antigens (ANCA) restricted to IgM class in three patients with systemic vasculitis. ANCA were detected by indirect immunofluorescence and isotype specific solid phase radioimmunoassay (SPRIA). Institution of immunosuppressive therapy was accompanied by an isotype switch to IgG ANCA and recovery in all three patients. In an associated study, ANCA activity was found in eluates from the washed glomeruli of two postmortem cases, with the same isotype distribution as was present in the sera. .A Jayne DR; Jones SJ; Severn A; Shaunak S; Murphy J; Lockwood CM. .I 200725 .U 90003955 .S Clin Nephrol 9001; 32(3):107-12 .M Adolescence; Blood Coagulation; Cell Count; Child; Child, Preschool; Fibrin/*AN; Glomerulonephritis, IGA/ME/*PA; Human; Macrophages/PA; Monocytes/*PA; Nephritis/ME/*PA; Purpura, Schoenlein-Henoch/ME/*PA; Support, Non-U.S. Gov't. .T Monocyte infiltration and cross-linked fibrin deposition in IgA nephritis and Henoch-Schoenlein purpura nephritis. .P JOURNAL ARTICLE. .W To clarify the role of immune cell infiltration and fibrin deposition in glomerular injury, renal biopsy specimens taken from patients with primary IgA nephritis and Henoch-Schonlein purpura nephritis (HSPN) were evaluated using monoclonal antibodies specific to mononuclear cell surfaces and cross-linked fibrin (XFb). Monocytes/macrophages were the predominant cell type infiltrating glomeruli in IgA nephritis and HSPN. The intraglomerular monocyte population in both diseases was significantly higher than that in normals, mesangial proliferative (non-IgA) glomerulonephritis or minimal change nephrotic syndrome. In IgA nephritis, there was a clear correlation between glomerular monocyte accumulation and the degree of proteinuria. Although the monocyte influx tended to decline with time in HSPN, it remained unchanged in IgA nephritis. XFb deposition was found in the glomeruli of 27 out of 48 patients with IgA nephritis, and in 15 out of 20 with HSPN. The degree of XFb deposition in IgA nephritis correlated significantly with the degree of mesangial proliferation. These findings indicate a close relationship of monocyte/macrophage infiltration and XFb deposition with glomerular injury in IgA nephritis. .A Yoshioka K; Takemura T; Aya N; Akano N; Miyamoto H; Maki S. .I 200726 .U 90003956 .S Clin Nephrol 9001; 32(3):113-8 .M Absorption; Acetazolamide/ME; Adult; Amiloride/ME; Biological Transport; Bumetanide/ME; Cell Membrane/ME; Chlorides/ME; Epithelium/ME; Human; Kidney/ME; Kidney, Polycystic/*ME; Sodium/*ME; Support, U.S. Gov't, P.H.S.. .T Cyst function in polycystic kidney disease: nongradient cysts. .P JOURNAL ARTICLE. .W Previous studies from this laboratory have demonstrated active sodium transport by cyst epithelia obtained from human polycystic kidneys. Cysts which maintained a steep sodium gradient between cyst fluid and plasma (gradient cysts) exhibited conductive amiloride sensitive sodium transport. Cysts which failed to maintain a sodium gradient between cyst fluid and plasma (nongradient cysts) were insufficiently characterized. In the present study, we report flux and electrical parameters of 23 nongradient cysts studied in vitro. Nongradient cysts exhibit low PD, low Isc, and high conductance. Unidirectional fluxes of sodium and chloride varied from approximately 14.4 to greater than 250 microEq.h-1.cm-2 and net flux was not significantly different from zero. There was no apparent effect on flux or electrical parameters of amiloride, ouabain, acetazolamide, or bumetanide. There was a very high correlation between unidirectional flux of sodium and chloride in individual cysts which was similar to the predicted relationship for diffusional fluxes. This correlation suggested that movement of sodium and chloride across cyst membranes was passive via an aqueous channel. Estimates of ionic permeability exceeded those determined for proximal nephron by almost one order of magnitude. We conclude that nongradient cysts are nonfunctional and, regardless of their origin, do not function analogously to the proximal nephron. .A Perrone RD; McLaughlin ML. .I 200727 .U 90003957 .S Clin Nephrol 9001; 32(3):119-23 .M Administration, Oral; Adolescence; Adult; Aged; Female; Glomerulonephritis/*PP; Glycosuria, Renal/PP; Guanidines/AD/*TU; Human; Male; Middle Age; Protease Inhibitors/AD/*TU; Proteinuria/*DT/ME/PP. .T Effect of camostat mesilate on heavy proteinuria in various nephropathies. .P JOURNAL ARTICLE. .W Camostat mesilate, a developed derivative of gabexate mesilate for oral use, was administered in a daily dose of 600 mg for 4 weeks to 17 patients with heavy proteinuria due to various nephropathies. Five patients had glomerulonephritis (3 patients with IgA nephropathy, one each with membranoproliferative GN and membranous nephropathy) and 3 had systemic vasculitis. These patients had been treated with glucocorticoid, cyclophosphamide, anticoagulants, and dipyridamole. Five patients had diabetic nephropathy and had been treated with conventional therapy including angiotensin converting enzyme inhibitors. Two cases with benign nephrosclerosis, one with Alport syndrome, and the rest with end-stage renal failure of undetermined cause were also included in this study. Urinary protein decreased promptly within 2 weeks (from 5.2 +/- 0.7 to 3.5 +/- 0.5, mean +/- SE, p less than 0.005), and serum total protein and albumin levels increased significantly. Serum creatinine levels did not change. Decreases in urinary protein excretion of more than 50% were observed in five out of eight patients with glomerulonephritis or systemic vasculitis, two out of five with diabetic nephropathy, and one with chronic renal failure. However, urinary protein excretion values remained at the same level in two patients with benign nephrosclerosis and a patient with Alport syndrome. We suggest that camostat mesilate caused a change in glomerular capillary permeability for macromolecules through its inhibitory effects on the kallikrein-kinin system, complement system, coagulation system, and platelet function, which contributed to the treatment of the various nephropathies. .A Matsubara M; Taguma Y; Kurosawa K; Hotta O; Suzuki K; Futaki G. .I 200728 .U 90003958 .S Clin Nephrol 9001; 32(3):124-8 .M Chromatography, High Pressure Liquid; Glutamine/BL/IP; Hemodialysis; Human; Support, Non-U.S. Gov't; Ultrafiltration; Uremia/*BL. .T Identification and determination of phenylacetylglutamine, a major nitrogenous metabolite in plasma of uremic patients. .P JOURNAL ARTICLE. .W Phenylacetylglutamine, a constituent of normal urine, was identified and quantitated in plasma ultrafiltrates from uremic patients. Its concentration ranged from 18 to 366 mumol/l, which shows a greater individual variation than those for the concentrations of urea and creatinine. The plasma level was reduced by hemodialysis. In ultrafiltrates from healthy subjects phenylacetylglutamine could not be detected with the methods used. Thus, it is a major nitrogenous metabolite that accumulates in uremia. A reverse phase HPLC method for the quantitative determination of phenylacetylglutamine in plasma ultrafiltrates is described. .A Zimmerman L; Egestad B; Jornvall H; Bergstrom J. .I 200729 .U 90003960 .S Clin Nephrol 9001; 32(3):133-8 .M Adult; Aged; Aged, 80 and over; Aluminum/*BL/UR; Bone and Bones/*AN; Dialysis Solutions/*AN; Female; Human; Kidney Failure, Chronic/*ME/TH; Male; Middle Age; Peritoneal Dialysis, Continuous Ambulatory/*; Regression Analysis. .T Aluminum concentrations in serum, dialysate, urine and bone among patients undergoing continuous ambulatory peritoneal dialysis (CAPD). .P JOURNAL ARTICLE. .W Aluminum (Al) concentration in serum, urine, and dialysate was estimated in 21 patients undergoing continuous ambulatory peritoneal dialysis (CAPD). In 12 of the patients bone Al concentration was measured as well. Mean serum Al level was 32.4 +/- 21.0 micrograms/l. The Al concentrations in the dialysate and urine were 9.1 +/- 4.1 micrograms/l and 52.5 +/- 47.3 micrograms/l, respectively. Bone Al concentration was 21.0 +/- 14.9 ppm and correlated significantly with concentrations of Al in serum (p less than 0.01) and dialysate (p less than 0.01). A mass transfer (MT) from the patients to the dialysate was observed in all patients (-44.0 +/- 28.8 micrograms/24 h). There was a highly significant correlation between peritoneal Al MT and serum Al (p less than 0.001), actual Al consumption (p less than 0.05) and bone Al concentration (p less than 0.005) supporting the existence of an overflow phenomenon. Despite very low Al levels in the dialysate, patients are at risk of elevated Al levels in the serum, dialysate, urine and bone because of consumption of Al-containing phosphate binders. .A Joffe P; Olsen F; Heaf JG; Gammelgaard B; Podenphant J. .I 200730 .U 90003961 .S Clin Nephrol 9001; 32(3):139-43 .M Adult; Aged; Aged, 80 and over; Cellulose/AA; Comparative Study; Disposable Equipment; Filtration/MT; Hemodialysis/*IS/MT; Human; Materials Testing; Membranes, Artificial/*; Middle Age; Polymers; Sulfones. .T Biocompatibility aspects of dialyzer reprocessing: a comparison of 3 re-use methods and 3 membranes. .P JOURNAL ARTICLE. .W While formalin reprocessing of cuprophan dialyzer membranes is known to improve their biocompatibility, the effects of different re-use methods have not been systematically investigated on different membranes. Therefore, the effects of reprocessing with formalin, hypochlorite-formalin and peracetic acid were successively investigated in 3 groups of 4 patients dialyzed on cuprophan (CU), cellulose acetate (CA) or polysulfone (PS). Leukocyte count, thrombocyte count and complement activation were studied during second and third use of the dialyzer. Formalin 3% storage was found to improve leukopenia, thrombocyte count and complement activation on CU but not on PS or CA where leukocyte and thrombocyte count worsened. Hypochlorite 1% rinsing prior to formalin 3% storage abolished the improvements observed on CU with formalin and induced on CA and PS the same leukopenia as formalin. In contrast, peracetic acid storage improved leukopenia, complement activation and thrombocyte count on the 3 membranes. In addition, it was found that storage of plasma-treated membrane fragments with peracetic acid abolished neutrophil oxygen radical production. Thus it appears that re-used membranes may not be systematically assumed to be more biocompatible, this property varying with both the type of membrane and the reprocessing technique. .A Kuwahara T; Markert M; Wauters JP. .I 200731 .U 90003962 .S Clin Nephrol 9001; 32(3):144-8 .M Adult; Case Report; Female; Hemodialysis/*AE; Human; Hyperparathyroidism, Secondary/CO; Kidney Failure, Chronic/TH; Male; Middle Age; Rupture, Spontaneous; Tendon Injuries/*ET/PA; Thigh/*. .T Spontaneous rupture of the quadriceps tendon in patients on maintenance hemodialysis--report of three cases with clinicopathological observations. .P JOURNAL ARTICLE. .W Three patients receiving maintenance hemodialysis therapy for end-stage renal failure presented with spontaneous rupture of the quadriceps tendon(s). Biochemical data and the skeletal roentgenograms were compatible with secondary hyperparathyroidism. Histological examination of the excised quadriceps tendon specimens suggested that repeated minor avulsion fractures of the bone cortex at the tendon insertion site had preceded the final total tendon rupture and that osteitis fibrosa was responsible for these minor fractures. Serum alkaline phosphatase level had been increasing continuously for approximately five years prior to the tendon rupture in all three patients, indicating that uncontrolled osteitis fibrosa due to secondary hyperparathyroidism over these years preceded the tendon rupture. .A Ryuzaki M; Konishi K; Kasuga A; Kumagai H; Suzuki H; Abe S; Saruta T; Takami H; Tashiro M. .I 200732 .U 90003963 .S Clin Nephrol 9001; 32(3):149 .M Female; Follow-Up Studies; Human; Kidney Failure, Acute/*CI; Lithium/*AE; Male; Mental Disorders/DT; Middle Age. .T Lithium-induced renal disease [letter; comment] .P COMMENT; LETTER. .A Carreras L; Gonzlez MT; Poveda R; Riera J; Bover J; Alsina J. .I 200733 .U 90003964 .S Clin Nephrol 9001; 32(3):149-50 .M Adolescence; Case Report; Female; Glomerulonephritis/*GE; Glomerulosclerosis, Focal/*GE; Human; Mosaicism; Turner's Syndrome/*GE. .T FSGS and mosaic Turner's syndrome [letter] .P LETTER. .A Chan PC; Cheng IK; Chan MK. .I 200734 .U 90003965 .S Clin Nephrol 9001; 32(3):150 .M Female; Glomerular Filtration Rate/DE; Human; Male; Middle Age; Nitrosourea Compounds/*PD; Organophosphorus Compounds/*PD; Renal Circulation/DE; Urodynamics/*DE. .T Renal hemodynamic and tubular effects of S 10036 (fotemustine) in man [letter] .P LETTER. .A Deray G; Khayat D; Bizzari JP; Jacquillat C. .I 200735 .U 90003979 .S Clin Orthop 9001; (247):101-5 .M Bone Neoplasms/*SU; Bone Wires; Case Report; Giant Cell Tumors/*SU; Human; Humerus/*SU; Ilium/*TR; Male; Movement; Pseudarthrosis; Shoulder/PP/RA; Transplantation, Heterotopic. .T Bone reconstruction after giant-cell tumor resection at the proximal end of the humerus with vascularized iliac crest graft. A report of three cases. .P JOURNAL ARTICLE. .W Giant-cell tumors at the proximal humerus were treated by wide excision and immediate bone replacement using free vascularized iliac crest grafts. The early results (30 months) in three patients have been satisfactory. .A Leung PC; Hung LK. .I 200736 .U 90003980 .S Clin Orthop 9001; (247):106-10 .M Bone Neoplasms/*SU; Case Report; Female; Giant Cell Tumors/*SU; Human; Humerus/*SU; Joint Prosthesis/*; Middle Age; Shoulder Joint. .T Prosthetic replacement due to giant-cell tumor in the proximal humerus. A case report. .P JOURNAL ARTICLE. .W A 45-year-old woman with an extensive giant-cell tumor of the right proximal humerus was treated by segmental resection and shoulder reconstruction. A Neer prosthesis and allogeneic bone grafts were used to reconstruct the shoulder joint. Autogeneic iliac bone was placed at the host-graft junction. The rotator cuff was reattached to the bone after making a semicircular trough. The long head of the biceps was reattached with stay sutures after making a trough between reattachments of the supraspinatus and the subscapularis. The patient regained almost full range of motion and excellent muscle power of the shoulder 60 months after operation. She did not have any difficulty with daily tasks of living. The prosthesis articulated with the glenoid well. There has been no evidence of tumor recurrence or metastasis. .A Takagishi K; Shinohara N. .I 200737 .U 90003981 .S Clin Orthop 9001; (247):111-6 .M Adult; Case Report; Human; Male; Scapula/*IN/SU; Wounds, Nonpenetrating/*SU. .T Treatment of painful scapulothoracic crepitus by resection of the superomedial angle of the scapula. A report of three cases. .P JOURNAL ARTICLE. .W Three healthy young male manual laborers developed painful unilateral scapulothoracic crepitus arising from the superomedial angle of the scapula. There was a history of trauma in two of the patients. Asymmetric prominence of the superomedial angle of the scapula was demonstrated by computed tomography (CT) scanning in two patients. All three patients were successfully treated by resection of the superomedial angle of the scapula. The resected tissue was histologically normal in each case. Painful scapulothoracic crepitus arising from the superomedial angle of the scapula is associated with local trauma, is best investigated with a CT scan, and if unresponsive to prolonged conservative measures, can be successfully treated by resection of the superomedial angle of the scapula. .A Richards RR; McKee MD. .I 200738 .U 90003982 .S Clin Orthop 9001; (247):117-23 .M Acromioclavicular Joint/*IN/PP/SU; Adult; Aged; Clavicle/*SU; Dislocations/PP/*SU; Female; Human; Male; Middle Age; Movement; Postoperative Complications. .T The influence of distal clavicle resection and rotator cuff repair on the effectiveness of anterior acromioplasty. .P JOURNAL ARTICLE. .W Anterior acromioplasty, described by Neer in 1972, is generally accepted as the procedure of choice for symptomatic subacromial impingement. Subsequent authors have written little about the prolonged length of postoperative rehabilitation, residual strength deficits, and the effect of the addition of a distal clavicle resection and/or rotator cuff repair. The authors reviewed 50 patients with late Neer Stage II and Stage III impingement lesions who were treated with anterior acromioplasty. In addition to the acromioplasty, 13 shoulders had a distal clavicle resection, nine had a rotator cuff repair, and ten had a distal clavicle resection and rotator cuff repair. The average patient age was 53 years (range, 36-70 years), and the average duration of symptoms was 43 months. Overall, 92% of the patients were graded as good or excellent on the basis of pain relief, strength, range of motion, and ability to resume full activity. Prolonged rehabilitation was noted in all groups, averaging 8.5 months; however, patients with a distal clavicle resection and rotator cuff repair required a 25% longer rehabilitation before full activity was obtained. A residual strength deficit was also noted in 70% of the patients requiring cuff repairs versus 50% in the patients with intact cuffs. Pain relief was equally obtained in all groups. .A Daluga DJ; Dobozi W. .I 200739 .U 90003983 .S Clin Orthop 9001; (247):124-6 .M Carpal Tunnel Syndrome/*CO; Case Report; Dermatitis, Contact/*ET; Female; Human; Median Nerve/*; Middle Age; Nerve Compression Syndromes/*ET. .T Dermatitis-sympathetic dysfunction in carpal tunnel syndrome. A case report. .P JOURNAL ARTICLE. .W A 52-year-old woman complained of numbness affecting the thumb, index, and middle fingers of both hands. The patient was managed with night splints with partial relief of symptoms. As a house cleaner, the patient was routinely exposed to water and detergents. About a year later, the patient developed contact dermatitis in the fingertips innervated by the median nerves. Electromyographic studies confirmed the presence of bilateral carpal tunnel syndrome. The temperature of all the fingertips was measured. The median innervated fingertips were warmer than those innervated by the ulnar nerves. The median sympathetic fibers may be compromized by compression in the carpal tunnel. This caused vasodilation, increased finger temperature, and lack of sweating in the median innervated fingers. Due to regular exposure to water and detergents, the susceptible dry fingertips developed contact dermatitis. The patient was managed conservatively, and the rash and numbness disappeared. .A Fast A; Parikh S; Ducommun EJ. .I 200740 .U 90003984 .S Clin Orthop 9001; (247):127-37 .M Adolescence; Adult; Child; Female; Follow-Up Studies; Hip Dislocation/PP/RA/*SU; Human; Male; Osteotomy/AE/*MT; Rotation. .T Rotational acetabular osteotomy for the severely dysplastic hip in the adolescent and adult. .P JOURNAL ARTICLE. .W Rotational acetabular osteotomy performed since 1968 is a circumacetabular osteotomy of the acetabulum for the dysplastic hip. The preoperative center-edge angle of Wiberg of 95 hips (89 patients) was -15 degrees or less. Forty-one hips (39 patients) form the basis of this report. They were followed from four years to 16 years and seven months (average, seven years and nine months). Twenty-one hips were classified as the Severin Group IV (subluxation) and 20 hips as the Severin Group V (a secondary acetabulum). A detailed assessment using a number of roentgenographic indices confirmed that the majority of the severely dysplastic hips could be corrected to nearly normal anatomy. The postoperative clinical results were assessed by the modified clinical classification of Severin proposed by Gibson and Benson. This procedure may be indicated for the severely dysplastic hip with subluxation or a secondary acetabulum in the adolescent and adult. .A Ninomiya S. .I 200741 .U 90003985 .S Clin Orthop 9001; (247):138-47 .M Adult; Aged; Bone Density; Female; Femur/*RA; Hip Prosthesis/*; Human; Hypertrophy; Male; Middle Age; Pain, Postoperative/*PC; Prosthesis Design; Stress, Mechanical. .T The effect of stem fit on bone hypertrophy and pain relief in cementless total hip arthroplasty. .P JOURNAL ARTICLE. .W This study was designed to clinically evaluate the effects of a tight distal fit and collar seating in hips with a cylindrical distal stem, collar, and proximal porous coating. A clinical assessment of pain and a roentgenographic assessment of patterns of proximal femoral hypertrophy were made in 105 patients. Intraoperative evaluations of the distal stem fit were performed so that a tight distal fit was ensured in 67 patients. Thirty-eight patients who did not have intraoperative sizing were determined roentgenographically to have a loose distal fit. Pain was significantly more likely to occur in those patients with a loose distal fit (20 of 38) than in those with a tight distal fit (two of 67). Collar seating was associated with hypertrophy under the seated portion of the collar in all cases, and failure to seat the collar was associated with recession and rounding of the upper femoral cortical edge. Distal hypertrophy occurred in 24 of the 67 hips with a tight distal fit, and a tight distal fit did not prevent proximal hypertrophy. It was concluded that a tight distal fit is associated with more complete pain relief in cementless total hip arthroplasty and that a tight distal fit of a cylindrical stem does not prevent proximal load bearing. .A Whiteside LA. .I 200742 .U 90003988 .S Clin Orthop 9001; (247):152-62 .M Adolescence; Adult; Aged; Comparative Study; Female; Femur Head Necrosis/*DI/RA; Human; Magnetic Resonance Imaging/*; Male; Middle Age; Predictive Value of Tests; Retrospective Studies; Tomography, Emission-Computed/*. .T Femoral head osteonecrosis. Detection by magnetic resonance imaging versus single-photon emission computed tomography. .P JOURNAL ARTICLE. .W Magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) examinations were compared for detection of femoral head osteonecrosis. Of 29 hips with clinical and roentgenographic evidence of osteonecrosis (18 histologically confirmed), 15 were Stage II, three transitional, six Stage III, and five Stage IV. MRI identified osteonecrosis in all 29 cases (100% sensitivity), and there were no false-positives (100% specificity). Of 24 osteonecrotic hips with technically adequate examinations, SPECT identified 14 (sensitivity 58%), and there were four false-positives (78% specificity). If Stages III and IV were eliminated, SPECT correctly identified ten of 15 (67% sensitivity). .A Miller IL; Savory CG; Polly DW Jr; Graham GD; McCabe JM; Callaghan JJ. .I 200743 .U 90003989 .S Clin Orthop 9001; (247):163-7 .M Adult; Aged; Aged, 80 and over; Anesthesia, Epidural/*; Bandages/*; Female; Hip Prosthesis/*; Human; Male; Middle Age; Osteoarthritis/*SU; Postoperative Complications/*PC; Thromboembolism/ET/*PC. .T Prevention of thromboembolism following elective hip surgery. The value of regional anesthesia and graded compression stockings. .P JOURNAL ARTICLE. .W Ninety-eight patients scheduled for elective hip arthroplasty receiving either general or regional anesthesia and graded compression stockings as the only thromboprophylactic treatment were screened for postoperative deep-venous thrombosis with 99mTc-plasmin scintimetry. The diagnosis of deep-venous thrombosis was established by phlebography and the diagnosis of pulmonary embolism by pulmonary perfusion and ventilation scintigraphy. Of 65 patients surgically treated under general anesthesia, 20 (31%) developed deep-venous thrombosis and six developed pulmonary embolism. Of 33 patients surgically treated using regional anesthesia, three (9%) developed deep-venous thrombosis and one developed a pulmonary embolus. The number of patients developing deep-venous thrombosis was significantly lower in the group receiving regional anesthesia compared with the group receiving general anesthesia. The results indicate the beneficial effects on the incidence of postoperative thromboembolic complications following elective hip surgery from the use of regional anesthesia and graded compression stockings. .A Wille-Jorgensen P; Christensen SW; Bjerg-Nielsen A; Stadeager C; Kjaer L. .I 200744 .U 90003990 .S Clin Orthop 9001; (247):168-74 .M Arthritis, Rheumatoid/SU; Gait; Human; Knee Joint/*PP; Knee Prosthesis/*; Movement/*; Osteoarthritis/SU; Prosthesis Design; Reoperation; Support, Non-U.S. Gov't. .T Effect of total knee arthroplasty on maximal flexion. .P JOURNAL ARTICLE. .W The advantage of potential flexion offered by total knee arthroplasty (TKA) is limited. In this review of 724 replaced knees, only one-third flexed to 105 degrees, while nearly one-half did not flex beyond 90 degrees. Postoperative flexion depended partly on preoperative flexion and partly on the prosthesis used, but these factors could not be the only determinants of results, for flexion in individual knees could increase, decrease, or remain unchanged whatever the preoperative measurement and whatever the design of prosthesis. Little difference in flexion before or after TKA was found between rheumatoid and osteoarthritic knees. Success or failure of the implant, according to the crude definition used, was not associated with degree of flexion. Patients with the lowest levels of function tended to have TKA with the least flexion and vice versa. Nevertheless, the degree of flexion is only one of the factors influencing mobility. .A Tew M; Forster IW; Wallace WA. .I 200745 .U 90003991 .S Clin Orthop 9001; (247):175-92 .M Human; Joint Instability/PC; Knee Injuries/*PC; Orthotic Devices/*; Prosthesis Design/*. .T Knee orthoses for valgus protection. Experiments on 11 designs with related analyses of orthosis length and rigidity. .P JOURNAL ARTICLE. .W Recent years have seen the introduction of a great many knee orthosis designs prescribed for protection against ligamentous injury or reinjury of the knee. The configurations and materials incorporated in these designs vary greatly, but all claim to be very effective. A leg model and 11 different commercially available knee orthoses were tested with static loading to obtain objective data on the relative effectiveness of the 11 designs to protect the knee from externally applied valgus moments. From these data, the effectiveness of each orthosis was calculated in terms of the rigidity contributed to the leg/orthosis combination. At a static valgus loading of 78 Nm, there was an eightfold variation in the rigidities contributed by the various knee orthoses, ranging from a low of 0.9 Nm per degree valgus to a maximum of 7.2 Nm per degree. The authors related analyses of two aspects of knee orthosis design (orthosis length and orthosis rigidity) to effectiveness in protecting against knee valgus overload injuries. Correlations were found between design inadequacies noted theoretically and efficacy problems evident from the laboratory tests. Orthosis length and orthosis rigidity must both be adequate, or the orthosis will not be biomechanically effective. .A Carlson JM; French J. .I 200746 .U 90003992 .S Clin Orthop 9001; (247):193-201 .M Adult; Aged; Biomechanics; Elasticity; Female; Human; Knee Joint/*PP; Knee Prosthesis; Male; Middle Age; Osteoarthritis/*PP; Support, Non-U.S. Gov't; Tibia/*PP. .T Stiffness of bone underlying the tibial plateaus of osteoarthritic and normal knees. .P JOURNAL ARTICLE. .W The mechanical properties of normal cancellous bone in the proximal tibia have been reported extensively in previous studies in terms of support of a total knee arthroplasty (TKA); yet, little is known about these mechanical properties in the osteoarthritic (OA) state. Fifteen normal and 28 OA tibial plateaus, obtained from autopsy or TKA, were mechanically tested using an indentor technique to assess the variation of stiffness patterns. The medial:lateral stiffness ratio calculated for the normal plateaus was significantly different from the ratios computed for specimens with medial compartment OA and lateral compartment OA; however, the ratio was unchanged in tricompartment OA. These data should receive greater consideration in the design of TKA, which has traditionally been designed on the mechanical properties of normal tibiae. .A Finlay JB; Bourne RB; Kraemer WJ; Moroz TK; Rorabeck CH. .I 200747 .U 90003993 .S Clin Orthop 9001; (247):202-7 .M Case Report; Female; Human; Knee Joint/*; Knee Prosthesis/*; Middle Age; Osteoarthritis/*ET/PA/SU; Osteopetrosis/*CO/PA. .T Osteoarthritis associated with osteopetrosis treated by total knee arthroplasty. Report of a case. .P JOURNAL ARTICLE. .W Osteopetrosis is due to a defect in osteoclastic cell function and results in osteosclerosis and progressive obliteration of the marrow spaces. Early onset osteoarthritis is associated with osteopetrosis. The authors describe a case of early onset osteoarthritis associated with osteopetrosis treated by total knee arthroplasty. The marblelike quality of osteopetrotic bone makes surgical treatment of these patients technically challenging and requires modification of standard surgical technique. .A Casden AM; Jaffe FF; Kastenbaum DM; Bonar SF. .I 200748 .U 90003994 .S Clin Orthop 9001; (247):208-19 .M Adolescence; Adult; Aged; Aged, 80 and over; Female; Human; Male; Middle Age; Recurrence; Retrospective Studies; Synovitis/*RA; Synovitis, Pigmented Villonodular/PA/*RA. .T Roentgenographic findings in pigmented villonodular synovitis of the knee. .P JOURNAL ARTICLE. .W Twenty-nine cases of pigmented villonodular synovitis (PVS) of the knee in 27 patients were reviewed to determine characteristic roentgenographic findings. All cases met strict histologic criteria for diagnosis. Four cases were localized PVS (LPVS), and 25 cases were diffuse PVS (DPVS). Roentgenographic findings were largely in the soft tissues. Cystic invasion of bone or degenerative changes were rare, although present in some cases. When present in DPVS, these changes were most pronounced in the patellofemoral articular surface. In the cases of DPVS, large posterior tumefactions did not correlate with extraarticular extension. Clinical behavior of PVS was governed more by anatomic site and form of disease than by the severity of histologic or roentgenographic findings. .A Flandry F; McCann SB; Hughston JC; Kurtz DM. .I 200749 .U 90003996 .S Clin Orthop 9001; (247):220-31 .M Animal; Bone Screws/*; Cattle; Elasticity; Equipment Design; Knee Prosthesis/*; Materials Testing/*; Polyurethanes. .T Analysis of the pull-out strength of screws and pegs used to secure tibial components following total knee arthroplasty. .P JOURNAL ARTICLE. .W The purpose of this study was to compare the pull-out forces of 3.8-mm and 6.5-mm diameter cancellous screws and a round peg 10 mm in diameter, implanted in bovine vertebral cancellous bone and two different grades of polyurethane. The relationships between the pull-out forces and the properties of the material into which they were inserted were also examined. For the same depth of insertion, the pull-out force of a 6.5-mm diameter screw was two times larger than that of a 3.8-mm diameter screw. Despite its smaller diameter, a 6.5-mm diameter screw demonstrated a pull-out force 13.6% greater than that of an optimally press-fitted 10-mm diameter round peg when both were inserted to the same depth; however, optimal compression for the peg was strongly dependent upon the size of predrilling and the modulus of elasticity of the material into which the peg was inserted. The pull-out force of a cancellous screw has a linear relationship with the shear strength of the material into which it is inserted. The pull-out force of a peg exhibits a linear relationship with the modulus of elasticity of the material into which it is inserted. .A Finlay JB; Harada I; Bourne RB; Rorabeck CH; Hardie R; Scott MA. .I 200750 .U 90003997 .S Clin Orthop 9001; (247):232-42 .M Biomechanics; Chronic Disease; Compliance; Female; Human; Joint Instability/*DI/PP; Knee Joint/*PP; Ligaments, Articular/*PP; Male; Orthopedic Equipment/*; Reference Values; Support, Non-U.S. Gov't. .T Anteroposterior drawer measurements in the knee using an instrumented test device. .P JOURNAL ARTICLE. .W A newly developed instrumented knee laxity tester was used to measure anteroposterior (AP) drawer parameters (Lachmann test) in populations of normal subjects and patients with anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) insufficiencies. The AP drawer tester features a differential electronic measuring procedure of displacements between patella and tuberosity over a continuous range between 180 and -180 N of AP forces. In the statistical evaluation, shift and compliance (or stiffness) parameters at various forces are considered. In a representative normal population, all relevant parameters were established, thus creating a normal data base for future reference. The average normal AP drawer shift between maximal anterior and posterior forces (180 N) was 6.4 +/- 1.7 mm. Right-left differences and male-female differences were found not to be statistically significant in any of the parameters. The validity of the instrumented drawer tester was confirmed relative to a group of patients with acute documented ligament insufficiencies. Measurements in two groups of patients with chronic postoperative knee instabilities revealed that although the diagnosis of instability could be confirmed, the results could hardly discriminate between ACL and PCL insufficiencies, probably due to unrecognized associated lesions at the time of operation and/or gradual postoperative developments of insufficiencies and deformities. An unexpected finding was that the mean laxities of the uninjured contralateral knees were significantly extended relative to the normal reference group, suggesting that these patients could have been classified as a high-risk group even before the time of injury. .A Edixhoven P; Huiskes R; de Graaf R. .I 200751 .U 90003998 .S Clin Orthop 9001; (247):243-55 .M Adolescence; Adult; Aged; Child; Combined Modality Therapy; Female; Follow-Up Studies; Human; Longitudinal Studies; Male; Middle Age; Recurrence; Retrospective Studies; Synovitis/*/PA/SU/TH; Synovitis, Pigmented Villonodular/*/PA/SU/TH. .T Pigmented villonodular synovitis. A retrospective review of affected large joints. .P JOURNAL ARTICLE. .W The experience, spanning 67 years, with 99 selected patients with pigmented villonodular synovitis of the knee, hip, elbow, or shoulder is reported. These patients were followed longitudinally for a mean of 13.5 years after the index operative procedure at the authors' institution. All but six of the patients still alive were contacted recently. The data were scrutinized for statistical significance by the Kaplan-Meier analysis and log-rank tests. Twenty-five patients had a recurrence after the index operative procedure. The probability of continuous recurrence-free survivorship at 25 years was 65%. Of the variables investigated for prognostic significance, only location in the knee, previous operative procedures, and incomplete surgical synovectomy were related significantly to a higher recurrence rate. .A Schwartz HS; Unni KK; Pritchard DJ. .I 200752 .U 90004000 .S Clin Orthop 9001; (247):261-71 .M Adolescence; Adult; Bone Neoplasms/*/RA/SU; Female; Human; Male; Middle Age; Neoplasm Recurrence, Local/SU; Osteoma, Osteoid/*/RA/SU; Pelvic Bones/*; Postoperative Complications; Support, Non-U.S. Gov't. .T Osteoid osteoma and osteoblastoma of the pelvis. .P JOURNAL ARTICLE. .W Benign osteoblastic tumors of the pelvis are rarely encountered in orthopedic practice. In most of the cases they involve the acetabular area, as was the case in nine of 14 cases of osteoid osteoma and osteoblastoma presented in this study. Especially with small tumors, such as osteoid osteomas, such a rare occurrence together with difficulties in the interpretation of roentgenograms can lead to mistakes and delays in diagnosis. To reduce these risks, a high grade of clinical suspicion and the use of tomograms or computed tomography (CT) scan and isotope bone scan are required. CT scan is an invaluable tool also for planning the surgical treatment in cases in which the tumor involves the acetabulum. Whereas an intracapsular excision is an adequate treatment for pelvic osteoid osteoma, pelvic osteoblastoma due to its size may need more aggressive surgery, even leading in some cases to a partial pelvic resection. The risk of recurrence is higher for osteoblastoma than for osteoid osteoma, as well as the rate of complications. .A Bettelli G; Capanna R; van Horn JR; Ruggieri P; Biagini R; Campanacci M. .I 200753 .U 90004004 .S Clin Orthop 9001; (247):290-6 .M Animal; Antineoplastic Agents, Combined/*PD; Cells, Cultured; Dihydroxycholecalciferols/*PD; Dose-Response Relationship, Drug; Drug Synergism; Hamsters; Mice; Osteosarcoma/*DT; Rats; Support, Non-U.S. Gov't; Tumor Cells, Cultured. .T 1 alpha,25(OH)2D3 exerts cytostatic effects on murine osteosarcoma cells and enhances the cytocidal effects of anticancer drugs. .P JOURNAL ARTICLE. .W The effects of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3), 1 alpha-hydroxyvitamin D3 (1 alpha(OH)D3), and dexamethasone on colony formation of Dunn osteosarcoma cells (TA 102 cells) were investigated. Concentrations of 1 alpha,25(OH)2D3, 1 alpha(OH)D3, and dexamethasone at which they exerted 50% reduction of the total area of TA 102 colony formation were 9 X 10(-9) M, 9 X 10(-8) M, and 5 X 10(-6) M, respectively. Effects of anticancer drugs on TA 102 cells were also investigated and concentrations needed for 50% growth inhibition (50% inhibitory concentration values) of cis-platinum, mitomycin C (MMC), methotrexate (MTX), and Adriamycin (ADR) against TA 102 cells were calculated to be 0.07 microgram/ml, 0.0008 microgram/ml, 0.0008 microgram/ml, and 0.0005 microgram/ml, respectively. The simultaneous treatment of TA 102 cells with 10(-8) M of 1 alpha,25(OH)2D3 and anticancer drugs significantly enhanced the respective inhibitory effects on colony formation. In this treatment, the IC50 value of MMC was calculated to be 6.4 X 10(-6) micrograms/ml, which was 1/160 of the expected IC50 value of MMC (8 X 10(-4) micrograms/ml). Similar synergistic effects were observed when the cells were treated with 1 alpha,25(OH)2D3 and low concentrations of cis-platinum, MTX, or ADR. .A Tanaka H; Yamamuro T; Kotoura Y; Matsumoto M; Tanaka C; Suzuki S; Tsuzi T; Miki T. .I 200754 .U 90004005 .S Clin Orthop 9001; (247):297-305 .M Animal; Biomechanics; Bone Lengthening/*; Fractures/ET; Osteogenesis/*; Osteotomy/*; Postoperative Complications/ET; Sheep; Support, Non-U.S. Gov't; Tibia/IN/RA. .T Lengthening osteotomy in the metaphysis and diaphysis. An experimental study in the ovine tibia. .P JOURNAL ARTICLE. .W In 20 sheep, aged seven to eight months, a tibial lengthening osteotomy was performed to compare the process of repair of the metaphyseal and diaphyseal regions of the bone. Analogous to clinical lengthening, two frame configurations of a bilateral external fixation device were used to obtain adequate fixation of the bone segments in the metaphyseal and diaphyseal lengthening osteotomies. A daily distraction rate of 1 mm for 4.5 weeks yielded an average length increase of 2.6 cm (12.5%). After death at 4.5 weeks postdistraction, the elongated bones were tested mechanically with the contralateral tibiae as controls. No significant difference in relative torsional strength of the elongated tibiae was found between the two groups. Inferior mechanical stability of the bone segments in metaphyseal compared with diaphyseal lengthening (due to differences in frame rigidity and distribution of muscular moments) influenced healing to such an extent that any superior biologic, osteogenic potential in the metaphyseal bone region was nullified. With the clinical use of two configurations of a given external device necessary for fixation of the bone segments in a metaphyseal or diaphyseal lengthening osteotomy, the empirically accepted idea that metaphyseal healing is superior may not be correct. .A Steen H; Fjeld TO. .I 200755 .U 90004007 .S Clin Orthop 9001; (247):306-12 .M Animal; Anti-Inflammatory Agents, Non-Steroidal/*PD; Clonixin/AA/*PD; Edema/*DT/ET; Female; Joint Diseases/*DT/ET; Nicotinic Acids/*PD; Piroxicam/*PD; Rabbits; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Tibial Fractures/*CO/PP/RA. .T The effects of two nonsteroidal antiinflammatory drugs on limb swelling, joint stiffness, and bone torsional strength following fracture in a rabbit model. .P JOURNAL ARTICLE. .W Using a rabbit distal tibia fracture model treated by immobilization for three weeks, the effects of two nonsteroidal antiinflammatory drugs on postfracture limb swelling, joint stiffness, and torsional bone strength were examined. Limb swelling in rabbits treated with low-dose piroxicam was reduced by 39%, and high-dose piroxicam reduced limb swelling by 86%. Flunixin, tested at one dose, reduced swelling by 53%. Neither piroxicam nor flunixin affected ankle stiffness or tibia torsional strength. .A More RC; Kody MH; Kabo JM; Dorey FJ; Meals RA. .I 200756 .U 90004014 .S Clin Orthop 9001; (247):80-6 .M Abnormalities, Multiple/*; Adolescence; Case Report; Family; Fingers/*AB; Human; Hyperopia/GE; Male; Pedigree; Spinal Stenosis/*GE; Syndactylia/GE; Toes/*AB. .T A pedigree of cervical stenosis, brachydactyly, syndactyly, and hyperopia. .P JOURNAL ARTICLE. .W Cervical myelopathy due to developmental cervical canal stenosis occurred in a 13-year-old boy. The patient's father and aunt also had an abnormally small cervical canal, although both were asymptomatic. The patient and his family had many congenital anomalies including hereditary brachydactyly, syndactyly, and hyperopia. The association of these anomalies seems not to have been previously reported in the literature. .A Iida H; Shikata J; Yamamuro T; Takeda N; Ueba Y. .I 200757 .U 90004015 .S Clin Orthop 9001; (247):87-9 .M Adult; Case Report; Fractures/*ET; Human; Lumbar Vertebrae/*IN; Male; Middle Age; Postoperative Complications/*ET; Recurrence; Repetition Strain Injury/*ET; Spinal Fusion/AE; Spondylitis, Ankylosing/*SU; Thoracic Vertebrae/*IN. .T Postsurgical recurrent stress fracture in the spine affected by ankylosing spondylitis. .P JOURNAL ARTICLE. .W Stress fracture in the dorsolumbar region is a well-known complication of the rigid spine usually occurring at the end stages of ankylosing spondylitis. When indicated, surgical treatment by anterior spinal fusion is prescribed. Three cases illustrating the appearance of new stress fractures in different parts of the spine after the successful anterior surgical fusion of a previous lesion indicate the possibility of recurrence. This explains the persistence of back pain postoperatively. These stress fractures seem unrelated to spinal deformities. External bracing is useful, but additional surgical fusions may become necessary. .A Ho EK; Chan FL; Leong JC. .I 200758 .U 90004016 .S Clin Orthop 9001; (247):90-6 .M Adolescence; Adult; Bone Wires/*; Human; Lumbar Vertebrae/*SU; Materials Testing; Middle Age; Orthopedic Fixation Devices/*; Spinal Diseases/SU; Thoracic Vertebrae/*SU. .T Segmental spinal instrumentation using short closed wire loops. .P JOURNAL ARTICLE. .W The Luque technique of segmental sublaminar instrumentation is now an established method of internal fixation in spinal surgery. The major difficulty encountered with the current technique is the danger of neurologic injury during the passage and handling of conventional wires, especially in extensive procedures. Great care is required to prevent inadvertent percussion of the wires already passed. The authors believe that by using short closed wire loops, these dangers have been minimized. Simple additional instrumentation has been devised to facilitate application of these loops. Apart from ease of application and handling, the short wire loops may offer a safer method of segmental sublaminar fixation. .A Mehdian H; Eisenstein S. .I 200759 .U 90004017 .S Clin Orthop 9001; (247):97-100 .M Adult; Arthrodesis/*MT; Brachial Plexus/IN; Female; Fracture Fixation/*IS; Human; Male; Shoulder Joint/IN/*SU. .T Shoulder arthrodesis by external fixation. .P JOURNAL ARTICLE. .W The choice of pin site in shoulder arthrodesis after brachial plexus injury is important for efficient external fixation. The pins are inserted into the coracoid process from the anterior aspect and the scapular spine from the acromion. This insertion method holds the scapula more rigid and allows the patient to lie supine. Moreover, it makes it possible to correct the fixation angle after the operation. In 11 cases of brachial plexus injury, solid bony arthrodesis was obtained within three months. .A Nagano A; Okinaga S; Ochiai N; Kurokawa T. .I 200760 .U 90004060 .S Clin Pediatr (Phila) 9001; 28(10):443-5 .M Bandages/*AE; Case Report; Child; Human; Male; Nose/*SU; Postoperative Complications/*; Shock, Septic/DI/DT/*ET. .T Toxic shock syndrome: associated with nasal packing. .P JOURNAL ARTICLE. .A Mansfield CJ; Peterson MB. .I 200761 .U 90004061 .S Clin Pediatr (Phila) 9001; 28(10):449-51 .M Age Factors; Child, Preschool; Convulsions, Febrile/*BL/PP; Creatine Kinase/*BL; Female; Human; Infant; Male; Prospective Studies; Time Factors. .T Elevated serum creatine kinase. Following febrile seizures. .P JOURNAL ARTICLE. .W Serum creatine kinase (CK) was determined in 52 children admitted following an episode of febrile convulsions. Enzyme levels correlated with the estimated duration of the seizure. Twenty-four hour values were significantly higher than those observed 1 hour after the convulsive episode. Serum CK levels are frequently used for diagnostic purposes, so the questionable validity of this test when drawn after a convulsive episode must be considered. .A Lahat E; Eshel G; Heyman E; Bar J; Katz Y; Aladjem M. .I 200762 .U 90004062 .S Clin Pediatr (Phila) 9001; 28(10):452-6 .M Adolescence; Adult; Female; Human; Infant, Newborn; Maternal Behavior/*/EH; Mother-Child Relations/*/EH; Parity; Pregnancy; Puerperium/*PX; Statistics. .T Development of positive feelings in primiparous mothers toward their normal newborns. A descriptive study. .P JOURNAL ARTICLE. .W Though mothers' development of positive feelings about their newborns is the first step in maternal attachment, little research has described factors which may influence the process. This descriptive study reports normative data for primiparous mothers with normal newborns. The authors interviewed 100 primiparous mothers on the postpartum ward within 72 hours after delivery at a community hospital to ascertain factors associated with the development of positive feelings. Over one third (39%) of mothers studied reported their first positive feeling during the prenatal period, 42 percent during birthing or the first day and 19 percent on the second or third day. A majority of mothers (70%) described their strong positive feelings toward their newborns (i.e., "love") as a sense of caring, commitment and concern. Several demographic, biological and environmental factors were associated with the development of first positive feelings in primiparous mothers. One half of mothers who planned to become pregnant developed positive feelings prenatally, while 57 percent of mothers who did not plan to become pregnant reported their first positive feelings during birth or the first day. Delay in first positive feelings until after the first day was associated with labor longer than 8 hours, disappointment with the "bonding" experience, breast-feeding, and high depressive symptoms. .A Pascoe JM; French J. .I 200763 .U 90004064 .S Clin Pediatr (Phila) 9001; 28(10):462-5 .M Adult; Child; Cholesterol/BL; Female; Human; Hyperlipidemia/*DI/EP/TH; Lipids/BL; Lipoproteins, HDL Cholesterol/BL; Lipoproteins, LDL Cholesterol/BL; Male; Middle Age; Prevalence; Triglycerides/BL. .T The child as proband. High prevalence of unrecognized and untreated hyperlipidemia in parents of hyperlipidemic children. .P JOURNAL ARTICLE. .W The authors evaluated the lipids of parents of hypercholesterolemic children to assess the prevalence of unrecognized and/or untreated hyperlipidemia. Biologic parents of 34 children had measurements of total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides (n = 47) or total cholesterol only (n = 14). Lipid abnormalities were defined according to guidelines established by the National Cholesterol Education Program. Abnormal values were defined as total cholesterol greater than 240 mg/dl, low-density lipoprotein (LDL) cholesterol greater than 160 mg/dl, HDL cholesterol less than 35 mg/dl, and triglycerides greater than 250 mg/dl. Borderline values were defined as total cholesterol between 200 and 240 mg/dl and LDL cholesterol between 130 and 160 mg/dl. Abnormal values were found in 32/61 (52%) and borderline values were found in 12/61 (20%) parents. Of the abnormal parents, 13/32 (41%) had unrecognized or known but untreated hyperlipidemia, and 9/12 (75%) of the borderline parents had unrecognized abnormalities. In all families where both parents were tested, at least 1 had a lipid abnormality. The authors conclude that when children with hypercholesterolemia are identified, parents should also have lipids assessed. Treatment programs for children should also be directed at the parents. .A Gidding SS; Whiteside P; Weaver S; Bookstein L; Rosenbaum D; Christoffel K. .I 200764 .U 90004065 .S Clin Pediatr (Phila) 9001; 28(10):466-9 .M Child; Child, Preschool; Cholesterol/*BL; Female; Human; Infant; Lipoproteins, HDL Cholesterol/BL; Lipoproteins, LDL Cholesterol/BL; Lipoproteins, VLDL Cholesterol/BL; Male; Phenylketonuria/BL/*DH; Triglycerides/*BL. .T Triglycerides, cholesterol, HDL, LDL, and VLDL cholesterol in serum of phenylketonuric children under dietary control. .P JOURNAL ARTICLE. .W Phenylketonuria is currently treated by a special diet to avoid elevated blood concentration of the essential amino acid phenylalanine. The authors examined 20 phenylketonuric children in the Inborn Error of Metabolism Department of Institute of Child Health in Athens. The children had simultaneous clinical and laboratory investigations. Blood cholesterol levels of these children were low in comparison with the levels of healthy children of the same age, but the triglyceride levels were higher as a result of a special diet containing a large amount of carbohydrates. Because of the triglyceride elevation the authors recommend supplementary vegetable fat intake, such as in olive oil, for their patients' dietary control. .A Schulpi KH; Scarpalezou A. .I 200765 .U 90004067 .S Clin Pediatr (Phila) 9001; 28(10):474-5 .M Case Report; Diagnosis, Differential; Female; Human; Infant, Newborn; Male; Tuberculosis, Pulmonary/ET/*RA; Tuberculosis, Urogenital/CO. .T Tuberculosis presenting in the neonatal period. .P JOURNAL ARTICLE. .A Schaaf HS; Smith J; Donald PR; Stockland B. .I 200766 .U 90004068 .S Clin Pediatr (Phila) 9001; 28(10):476-8 .M Brucellosis/*DI/ET/PA; Case Report; Central Nervous System/PA; Central Nervous System Diseases/*DI/PA; Diagnosis, Differential; Human; Infant; Male. .T Brucellosis of the central nervous system. A case report of an infected infant. .P JOURNAL ARTICLE. .W Brucellosis in early infancy is unusual and reports of congenitally acquired infection are extremely rare. The patient presented at the age of 8 months with high fever and signs of meningitis. He had a previous history of hydrocephalus undergoing shunt alleviation at 1 month of age. A diagnosis of central nervous system (CNS) brucellosis was subsequently made. Transplacental transmission is offered as a possible explanation for the acquisition of this child's brucellosis infection. .A Drutz JE. .I 200767 .U 90004069 .S Clin Pediatr (Phila) 9001; 28(10):480-1 .M Case Report; Exchange Transfusion, Whole Blood/*; Female; Human; Infant; Polyradiculoneuritis/*CO; Respiratory Paralysis/*ET/TH. .T Recovery from respiratory paralysis caused by Guillain-Barre syndrome in an infant after repeated exchange transfusions. .P JOURNAL ARTICLE. .A Singh S; Singhi S. .I 200768 .U 90004070 .S Clin Pediatr (Phila) 9001; 28(10):482-3 .M Child, Preschool; Diarrhea/PP; Gastroenteritis/PP; Hemolytic-Uremic Syndrome/*PP; Human; Infant. .T The homogeneous nature of the hemolytic uremic syndrome. .P JOURNAL ARTICLE. .A Havens PL; Hoffman GM; Shith KJ. .I 200769 .U 90004073 .S Clin Pharmacol Ther 9001; 46(4):387-9 .M Automatic Data Processing/*TD; Drug Therapy/*AE; Human; Medical Record Linkage/*MT; Medical Records; Product Surveillance, Postmarketing/*TD. .T The future of automated record linkage for postmarketing surveillance: a response to Shapiro. .P JOURNAL ARTICLE. .A Faich GA; Stadel BV. .I 200770 .U 90004074 .S Clin Pharmacol Ther 9001; 46(4):390-4 .M Aged; Automatic Data Processing/*; Drug Therapy/*AE; Epidemiologic Methods; Human; Product Surveillance, Postmarketing/*SN; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Automated data bases used for pharmacoepidemiology research. .P JOURNAL ARTICLE. .A Strom BL; Carson JL. .I 200771 .U 90004075 .S Clin Pharmacol Ther 9001; 46(4):395-8 .M Automatic Data Processing/*TD; Drug Therapy/*AE; Epidemiologic Methods; Human; Medical Record Linkage/*MT; Medical Records; Product Surveillance, Postmarketing/*MT. .T Automated record linkage: a response to the commentary and letters to the editor. .P JOURNAL ARTICLE. .A Shapiro S. .I 200772 .U 90004076 .S Clin Pharmacol Ther 9001; 46(4):399-407 .M Adult; Caffeine/AD; Cotinine/BL/UR; Diet; Female; Half-Life; Human; Infusions, Intravenous; Male; Metabolic Clearance Rate; Nicotine/BL/UR; Theophylline/BL/*PK; Tobacco Smoke Pollution/*. .T Effects of passive smoking on theophylline clearance. .P JOURNAL ARTICLE. .W Theophylline disposition was examined in seven passive smokers, defined as nonsmokers with long-term exposure to cigarette smoke, and seven age-matched nonsmokers with minimal smoke exposure. Subjects were given an intravenous infusion of aminophylline (6 mg/kg) and blood samples were drawn before and during the 48-hour postinfusion period. Clearance for passive smokers was 6.01 x 10(-2) L/hr.kg and for nonsmokers, clearance was 4.09 x 10(-2) L/hr.kg (p less than 0.025). Terminal elimination half-life for passive smokers was 6.93 hours versus 8.69 hours for nonsmokers (p less than 0.05). The mean residence time for passive smokers was 9.89 hours. For nonsmokers, the mean residence time was 13.11 hours (p less than 0.05). These measurements were statistically different, whereas there was no difference in volume of distribution between the groups, suggesting that passive smokers metabolize theophylline more rapidly than nonsmokers. Plasma and urine cotinine and nicotine concentrations were measured in all subjects. There was a significant difference between the subject groups in plasma (p less than 0.004) and urine (p less than 0.002) cotinine concentrations. Theophylline clearance correlated with both plasma (r = 0.73, p less than 0.01) and urine (r = 0.79, p less than 0.01) cotinine concentrations. Additional studies should be conducted to further define the pharmacokinetic characteristics of passive smokers and to assess the effects of passive smoking on drugs metabolized by the mixed function oxidase system. .A Matsunga SK; Plezia PM; Karol MD; Katz MD; Camilli AE; Benowitz NL. .I 200773 .U 90004077 .S Clin Pharmacol Ther 9001; 46(4):408-19 .M Administration, Oral; Adult; Chromatography, High Pressure Liquid; Diltiazem/AA/AD/BL/PD/*PK; Half-Life; Human; Male; Protein Binding; Support, U.S. Gov't, P.H.S.. .T The pharmacokinetics and pharmacodynamics of diltiazem and its metabolites in healthy adults after a single oral dose. .P JOURNAL ARTICLE. .W A potential complicating factor in the characterization of the pharmacokinetics and pharmacodynamics of diltiazem after an oral dose in the presence of two metabolites, N-demethyldiltiazem and desacetyldiltiazem, in plasma. Both N-demethyldiltiazem and desacetylditiazem have been shown to have pharmacologic activity in animal tissues. It is therefore possible that these metabolites contribute to the pharmacologic effect of diltiazem, but this possibility has not been explored. The purpose of this study was to investigate the pharmacokinetics and pharmacodynamics of diltiazem, N-demethyldiltiazem, and desacetyldiltiazem. Particular attention was paid to the effect of diltiazem on atrioventricular conduction. Six healthy men received a 120 mg oral dose of diltiazem. Concentrations of diltiazem, N-demethyldiltiazem, and desacetyldiltiazem in plasma and urine were measured by a sensitive HPLC method. Measures of pharmacologic response (heart rate, blood pressure, and PR interval) were obtained at each blood sampling time. Mean (+/- SD) peak plasma concentrations of diltiazem, N-demethyldiltiazem, and desacetyldiltiazem were 174.3 +/- 72.7, 42.6 +/- 10.0, and 14.9 +/- 3.3 ng/ml, respectively. The apparent half-lives of diltiazem, N-demethyldiltiazem, and desacetyldiltiazem were 6.5 +/- 1.4 hours, 9.4 +/- 2.2 hours, and 18 +/- 6.2 hours, respectively. Both N-demethyldiltiazem and diltiazem were eliminated by net secretion, whereas the renal clearance of desacetyldiltiazem did not exceed clearance by filtration. Both N-demethyldiltiazem and desacetyldiltiazem are bound to plasma proteins, with unbound fractions of 0.323 +/- 0.035 and 0.230 +/- 0.021. These values are similar to the unbound fraction of diltiazem (0.254 +/- 0.027). No significant effect of diltiazem on blood pressure or heart rate was noted. However, a prolongation of the PR interval was observed in all six subjects. Furthermore, an apparent clockwise hysteresis in the concentration-effect relationship was found in four of the six subjects. These findings suggest that some form of acute tolerance to the electrophysiologic effect of diltiazem develops, but the results of pharmacodynamic modeling suggest that this is not caused by the antagonistic effects the metabolites. .A Boyd RA; Chin SK; Don-Pedro O; Verotta D; Sheiner LB; Williams RL; Giacomini KM. .I 200774 .U 90004078 .S Clin Pharmacol Ther 9001; 46(4):420-8 .M Adult; Chromatography, High Pressure Liquid; Drug Interactions; Enoxacin/*AD/BL/PD; Human; Male; Middle Age; Support, Non-U.S. Gov't; Theophylline/BL/*PK/UR; Time Factors; Xanthines/BL/UR. .T The theophylline-enoxacin interaction: II. Changes in the disposition of theophylline and its metabolites during intermittent administration of enoxacin. .P JOURNAL ARTICLE. .W The pharmacokinetics of theophylline and its three major metabolites, 3-methylxanthine, 1-methylurate, and 1,3-dimethylurate, were studied during intermittent administration of enoxacin. The addition of enoxacin (400 mg, twice daily) to a theophylline dosing regimen (150 mg, twice daily) resulted in an immediate fall in plasma theophylline metabolite concentrations. Mean steady-state theophylline concentration in plasma during the dosing interval increased from 3.17 to 8.23 micrograms/ml. The mean 12-hour recovery of total theophylline metabolite decrease from 76.3 to 38.6 mg. After the discontinuation of enoxacin, but not theophylline, the plasma theophylline metabolite levels immediately increased to near or above the concentrations observed before enoxacin coadministration. Concurrently, theophylline concentrations decreased to levels equivalent to those observed before enoxacin coadministration. In general, the changes in plasma theophylline concentrations observed after the addition of discontinuation of enoxacin were complete within 3 days. .A Rogge MC; Solomon WR; Sedman AJ; Welling PG; Koup JR; Wagner JG. .I 200775 .U 90004079 .S Clin Pharmacol Ther 9001; 46(4):429-39 .M Adenosine Cyclic Monophosphate/AN; Adult; Cell Separation; Female; Flow Cytometry/MT; Human; Leukocyte Count; Lymphocytes/*/AN; Magnetics; Male; Receptors, Adrenergic, Beta/*DE; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Terbutaline/*PD. .T A new method for isolation of human lymphocyte subsets reveals differential regulation of beta-adrenergic receptors by terbutaline treatment. .P JOURNAL ARTICLE. .W We adapted a technique for isolation of mononuclear leukocyte (MNL) subsets with immunomagnetic beads to the study of beta-adrenergic receptors. Mixed MNL cells were sequentially incubated with monoclonal antibodies specific for certain MNL subsets. Sheep antimouse antibodies coupled to magnetic beads were then added, and the desired MNL subset was pulled out with a magnet. This method yielded subsets with high purity and did not alter beta-receptor density or function. Healthy volunteers were treated for 7 days with the beta 2-selective agonist terbutaline (5 mg t.i.d.). Terbutaline treatment decreased beta-receptor number and isoproterenol-stimulated cyclic adenosine monophosphate (cAMP) generation in natural killer cells, helper T cells, and suppressor/cytotoxic T cells but not in B cells. The decrease was greatest in suppressor/cytotoxic T cells and least in helper T cells. Thus beta-adrenergic receptor regulation by agonists appears to differ among MNL subsets. .A Maisel AS; Fowler P; Rearden A; Motulsky HJ; Michel MC. .I 200776 .U 90004080 .S Clin Pharmacol Ther 9001; 46(4):440-4 .M Adult; Aged; Blood Pressure/*DE; Dinoprostone/UR; Double-Blind Method; Drug Administration Schedule; Electrocardiography, Ambulatory/DE; Electrolytes/UR; Female; Human; Hydrochlorothiazide/AI/*TU; Hypertension/*DT; Ibuprofen/AD/*PD; Middle Age; Radioimmunoassay; Random Allocation. .T The effect of high-dose short-term ibuprofen on antihypertensive control with hydrochlorothiazide. .P JOURNAL ARTICLE. .W The effect of high-dose ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID), on the blood pressure of treated hypertensive patients was evaluated in a randomized, placebo-controlled, double-blind, crossover trial with 24-hour ambulatory blood pressure monitoring. Twelve middle-aged black women with essential hypertension, controlled with 50 mg hydrochlorothiazide per day, randomly received 3200 mg ibuprofen and a placebo for 8 days. Each treatment phase was separated by a 1-week washout period. Ambulatory blood pressure monitoring (ABPM), body weight, and 24-hour urinary excretion of sodium, creatinine, and prostaglandin E2 (PGE2) were determined at the end of each treatment phase. Mean (+/- SEM) 24-hour systolic and diastolic blood pressures were 122/85 (+/- 2.9/1.7) and 125/85 (+/- 3.0/1.1) during the placebo and ibuprofen phases, respectively. Mean ABPM during six consecutive 4-hour periods also revealed no significant differences between placebo and ibuprofen. We conclude that 3200 mg ibuprofen per day for up to 1 week induced little change in blood pressure in hypertensive who are receiving hydrochlorothiazide. .A Wright JT; McKenney JM; Lehany AM; Bryan DL; Cooper LW; Lambert CM. .I 200777 .U 90004082 .S Clin Pharmacol Ther 9001; 46(4):451-7 .M Adult; Aged; Bayes Theorem; Ciprofloxacin/BL/*PK/UR; Critical Care/*; Female; Human; Infusions, Intravenous; Kidney/ME; Male; Middle Age; Prospective Studies; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Wounds and Injuries/EP/*ME. .T Prospective use of optimal sampling theory: steady-state ciprofloxacin pharmacokinetics in critically ill trauma patients. .P JOURNAL ARTICLE. .W We examined the use of optimal sampling theory to determine a sparse sampling design to estimate pharmacokinetic parameters of ciprofloxacin in patients who had sustained trauma. Two serum sampling strategies, consisting of six sampling times each, were derived on the basis of the patient's renal function (patients with creatinine clearance greater than or equal to 6 L/hr/1.73 m2 and patients with creatinine clearances less than 6 L/hr/1.73 m2). Two additional serum samples were obtained for other aspects to the study. A timed urine collection was also obtained. Pharmacokinetic parameter estimates were determined by comodeling the serum and urine data with a three-compartment open model (parameterized as microconstants) with a bayesian algorithm and by noncompartmental analysis. Bayesian-derived parameter estimates were total body clearance of drug from plasma, 29.8 L/hr/1.73 m2; renal clearance, 17.0 L/hr/1.73 m2; and nonrenal clearance, 12.7 L/hr/1.73 m2 and were not significantly different from noncompartmentally derived parameters (p = 0.80, p = 0.65 and p = 0.333, respectively). The study demonstrates the use of optimal sampling theory to determine an informative yet relatively sparse sampling strategy for a drug with a complex pharmacokinetic model. .A Yuen GJ; Drusano GL; Forrest A; Plaisance K; Caplan ES. .I 200778 .U 90004083 .S Clin Pharmacol Ther 9001; 46(4):458-62 .M Analgesics/BL/*PK/TU; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fentanyl/*AA/BL/PK/TU; Human; Injections, Epidural; Male; Middle Age; Pain/*DT; Random Allocation; Respiration/*DE; Support, Non-U.S. Gov't. .T Relationship between the pharmacokinetics and the analgesic and respiratory pharmacodynamics of epidural sufentanil. .P JOURNAL ARTICLE. .W To establish the relationships between epidural sufentanil analgesia and respiratory effects and to determine the pharmacokinetics of the drug, 22 adult patients undergoing thoracotomy were put into a randomized, double-blind study and received either 30, 50, or 75 micrograms per dose in 20 ml normal saline solution. Repeated doses were given on request for the 24-hour study period. There was a weak but significant nonlinear correlation between length of effective analgesia and the cumulative dose of the drug (r = 0.26, p less than 0.001). In 12 of 22 patients, the maximal length of effective analgesia was reached before the last dose and the effect tended to taper off thereafter. The mean maximal length of effective analgesia was 4.69 +/- 0.32 hours (mean +/- SEM), whereas the length of effective analgesia with the last dose was only 3.34 +/- 0.46 hours (p less than 0.0005). There was a significant correlation between the peak serum concentrations of sufentanil during the dose interval and the length of effective analgesia (r = 0.44, p less than 0.0001). Area under the concentration-time curve was proportional to the size of the epidural dose, and with all three doses tested there was a gradual accumulation of sufentanil in the serum. Mean time-to-peak concentration (tmax) increased with repeated doses (p less than 0.05). Mean serum concentration of sufentanil during periods of slow respiratory rate (0.47 +/- 0.05 ng/ml) was significantly higher than during episodes without adverse respiratory effects (0.37 +/- 0.05 ng/ml, p less than 0.05). The above data suggest that an important part of the analgesic and adverse effects of sufentanil are mediated centrally, after this opioid is absorbed systemically. .A Koren G; Sandler AN; Klein J; Whiting WC; Lau LC; Slavchenko P; Daley D. .I 200779 .U 90004084 .S Clin Pharmacol Ther 9001; 46(4):463-8 .M Administration, Oral; Adult; Aged; Dietary Fats/*PD; Fasting; Female; Human; Intestinal Absorption/*DE; Male; Middle Age; Morphine/AD/BL/*PK/TU; Pain/*DT; Support, Non-U.S. Gov't. .T Influence of a high-fat meal on the absorption of morphine from oral solutions. .P JOURNAL ARTICLE. .W The influence of a high-fat meal on blood morphine concentrations after the administration of a morphine solution (50 mg dose) was studied in 12 patients with chronic pain. The oral morphine dose was administered in a total volume of 200 ml to patients either immediately after food intake or while in the fasting state. There was a 34% increase in the area under the curve (AUC) when morphine was administered immediately after food when compared with the fasting state (p less than 0.02). However, there was no significant difference between the maximum blood morphine concentration (Cmax) or the time to maximum concentration (tmax) between the two treatment regimens. The shape of the blood morphine concentration-time curve was consistently altered in the fed patients compared with patients who were in the fasting state, inasmuch as the blood morphine concentrations were maintained at a higher level from 240 to 600 minutes after the dose when the morphine was administered with food (p less than 0.02). It is suggested that morphine concentrations are maintained at higher levels, possibly resulting in more prolonged pain relief, when morphine is administered with food compared with the same dose administered to patients who are in the fasting state. .A Gourlay GK; Plummer JL; Cherry DA; Foate JA; Cousins MJ. .I 200780 .U 90004085 .S Clin Pharmacol Ther 9001; 46(4):469-77 .M Administration, Oral; Adult; Double-Blind Method; Drug Synergism; Exertion; Hemodynamics/*DE; Human; Male; Propranolol/*AE/BL/PK; Random Allocation; Support, Non-U.S. Gov't; Verapamil/AA/*AE/BL/PK. .T Synergistic adverse hemodynamic interaction between oral verapamil and propranolol. .P JOURNAL ARTICLE. .W The interaction between oral verapamil and propranolol may involve negative chronotropic, inotropic or dromotropic effects. The immediate effects of orally administered verapamil (120 mg) and propranolol (80 mg), alone and combined, on submaximal exercise hemodynamics and on pharmacokinetics were studied in eight healthy male volunteers in a randomized, double-blind, crossover manner. Maximum effects on heart rate, systolic blood pressure, PR interval and rate-adjusted PR prolongation were greatest with the combined administration of verapamil and propranolol. The combination caused a high frequency of adverse drug events, predominantly exercise fatigue. Verapamil increased the AUC and Cmax and shortened the tmax of propranolol. Propranolol decreased the AUC and Cmax of verapamil. The greater reduction of heart rate with the combination of verapamil and propranolol was only partially explained by higher plasma concentrations of propranolol. The combination of propranolol and verapamil produced clinically important synergistic adverse effects during exercise. Negative dromotropic effects occurred primarily by direct AV node inhibition and were more important than previously recognized. .A Carruthers SG; Freeman DJ; Bailey DG. .I 200781 .U 90004086 .S Clin Pharmacol Ther 9001; 46(4):478-9 .M Automatic Data Processing/*; Epidemiologic Methods; Human; Medical Record Linkage/*MT; Medical Records; Product Surveillance, Postmarketing/*MT. .T Uninformed criticism of automated record linkage [letter] .P LETTER. .A Vick H; Walker AM. .I 200782 .U 90004087 .S Clin Pharmacol Ther 9001; 46(4):479-80 .M Automatic Data Processing/*; Human; Medical Record Linkage/*MT; Medical Records; Product Surveillance, Postmarketing/*MT; United States; United States Food and Drug Administration. .T Record linkage for postmarketing surveillance [letter] .P LETTER. .A Faich GA. .I 200783 .U 90004088 .S Clin Pharmacol Ther 9001; 46(4):480 .M Epidemiologic Methods; Human; Medical Record Linkage/*MT; Medical Records; Product Surveillance, Postmarketing/*MT. .T Pharmacoepidemiology: the lessons learned; the challenges ahead [letter] .P LETTER. .A Tilson HH. .I 200784 .U 90004164 .S Clin Lab Med 9001; 9(3):369-593 .M Diagnosis, Laboratory/*; Human; Sexually Transmitted Diseases/*DI. .T Sexually transmitted diseases. .P JOURNAL ARTICLE. .I 200785 .U 90004276 .S Contact Dermatitis 9001; 21(3):129-33 .M Dermatitis, Atopic/*ET; Female; Human; Hypersensitivity, Immediate/*ET; Nickel/*AE; Respiratory Function Tests; Skin Tests/*. .T Atopy in subjects with a history of nickel allergy but negative patch tests. .P JOURNAL ARTICLE. .W Various markers of atopy were studied in 20 subjects with a history of nickel allergy but negative patch test reactions, and compared with 2 control groups: 13 subjects with no history of nickel allergy and negative patch tests; 11 subjects with a history of nickel allergy and positive patch tests. No significant difference in the incidence of atopy was detected in the 3 groups. .A Todd DJ; Burrows D; Stanford CF. .I 200786 .U 90004277 .S Contact Dermatitis 9001; 21(3):134-40 .M Alcohols, Butyl/*ME; Animal; Guinea Pigs; Hydrocarbons, Chlorinated/*ME; Ointments/TU; Skin Absorption/*/DE; Solvents/ME; Support, Non-U.S. Gov't; Time Factors; Toluene/*ME. .T Percutaneous absorption of 3 organic solvents in the guinea pig. (III). Effect of barrier creams. .P JOURNAL ARTICLE. .W The efficacy of 4 barrier preparations presented as cream or foam against percutaneous absorption of organic solvents was investigated in the guinea pig. An ordinary hand cream was also tested. Slight reduction in blood concentration of the solvents was seen when normal skin treated with barrier creams was exposed. Absorption of butanol through stripped skin treated with barrier creams was higher than absorption through skin not so treated. Barrier creams can be considered to give poor skin protection against the organic solvents investigated. .A Boman A; Mellstrom G. .I 200787 .U 90004278 .S Contact Dermatitis 9001; 21(3):141-7 .M Animal; Comparative Study; Cosmetics/AE; Coumarins/*AE; Dermatitis Medicamentosa; Dermatitis, Contact/*ET; Dyes; Female; Guinea Pigs; Lasers; Perfume/AE; Scopoletin/AE; Support, Non-U.S. Gov't; Umbelliferones/AE; 4-Hydroxycoumarins/AE. .T The sensitizing capacity of coumarins (III). .P JOURNAL ARTICLE. .W 9 coumarins used as chemical reagents, laser dyes, in perfumery, cosmetics or occurring naturally, were investigated experimentally in guinea pigs to determine their contact sensitizing capacity. 5,7-dihydroxycoumarin, limettin and 5,7-dihydroxy-4-methylcoumarin were found to be moderate sensitizers, while scoparone, isoscopoletin and 4-hydroxycoumarin were weak. The 3 laser dyes were completely negative. The results indicate that substitution in the 6 and 7 or 5 and 7 positions with 2 hydroxy groups supports allergenic capability, while other substituents (e.g., methoxy groups) in the same positions, or an additional (third) substituent, diminish activity. .A Hausen BM; Berger M. .I 200788 .U 90004279 .S Contact Dermatitis 9001; 21(3):148-53 .M Climate; Dermatitis, Contact/*DI; Female; Hong Kong; Human; Male; Patient Acceptance of Health Care; Skin Tests/*; Support, Non-U.S. Gov't. .T Patch testing in Hong Kong. .P JOURNAL ARTICLE. .W The acceptability and value of patch testing in Hong Kong was studied in 56 cases of suspected dermatitis (CD), 26 cases of endogenous eczema (EE) and 30 cases of unclassified eczema (UE), selected systematically: all those suspected of having CD and 1 in 3 of the others. 81.3% of the 112 patients selected accepted the test. The main reasons for refusal were inconvenience and lack of time for the readings. Of the 91 tested, in 88 they were successfully completed. In 39 patients, the results were negative, while 49 patients reacted to 1 or more allergens. The 2 commonest sensitizers were fragrance-mix (15 patients) and nickel sulphate (14 patients). The "usefulness" of patch testing was defined as it causing the initial clinical diagnosis to be changed. The test was found to be "useful" in 10 cases (21.3%) of those diagnosed as CD in 2 respects: (a) changing the diagnosis from irritant to allergic CD (6 cases) and (b) changing the diagnosis from CD to a suspected substance, to CD to another unsuspected substance (4 cases). For EE and UE, the initial diagnosis was changed to allergic CD in 3 (18.7%) and 7 (28.0%) cases, respectively. .A Lee TY; Lam TH. .I 200789 .U 90004280 .S Contact Dermatitis 9001; 21(3):154-8 .M Adult; Dermatitis Medicamentosa/*; Female; Glycols/*AE; Human; Male; Propanediols/*AE; Skin/*DE; Skin Tests; Ultrasonics; Water Loss, Insensible. .T Skin reactions to hexylene glycol. .P JOURNAL ARTICLE. .W Hexylene glycol (HG), which has been used for years in industrial chemicals and cosmetics, has recently been introduced in topical corticosteroids. We studied the irritant and sensitizing properties of HG in eczema patients. HG at 50% or 30% and propylene glycol (PG) at 30% in water were patch tested in 823 eczema patients subjected to routine patch testing. Oedema and erythema reactions from HG occurred in 2.8% of the patients. The corresponding result for PG was 3.8%. 50% HG equalled 30% PG in producing a visible reaction. In patch tests with dilution series, 2 patients reacted to 1% HG, but in both cases ROAT with HG remained negative. One other patient with a 3+ patch test reaction to both 30% PG and 50% HG had a positive ROAT result to 30% HG in water and to 5% PG in a cream base. PG, but not HG, increased transepidermal water loss both in atopic normal-looking skin and among healthy controls. The present results suggest that HG is less irritating that PG under occlusion, but that delayed contact allergic reactions may occur. .A Kinnunen T; Hannuksela M. .I 200790 .U 90004281 .S Contact Dermatitis 9001; 21(3):159-65 .M Adrenal Cortex Hormones/*AE; Cross Reactions; Dermatitis Medicamentosa/DI/ET; Dermatitis, Contact/DI/*ET; Dermatologic Agents/AE; Human; Hydrocortisone/*AA; Hydrocortisone, Topical/*AE; Skin Tests; Support, Non-U.S. Gov't. .T Detection of contact hypersensitivity to topical corticosteroids with hydrocortisone-17-butyrate. .P JOURNAL ARTICLE. .W We showed earlier that most patients with contact dermatitis due to corticosteroids show cross-reactions when patch tested with hydrocortisone-17-butyrate (H-17-B). To test whether H-17-B could be used for detecting topical corticosteroid allergy, we screened patients undergoing routine patch testing with H-17-B. Patients with clearly allergic or doubtful/mildly irritant patch test reactions to H-17-B, and with a history suggesting topical corticosteroid allergy, were further tested with a large panel of steroid preparations. 20 out of 4039 patients (0.5%) showed definite allergic test reactions to corticosteroids. A further 165 patients with clinically suspected corticosteroid allergy were directly tested with a panel of steroid preparations; 14 patients showed positive patch test reactions. Altogether, 33 out of 34 patients with corticosteroid allergy had positive test reactions to H-17-B. Inclusion of 1.0% H-17-B in ethanol in the standard patch test series improves the diagnosis of topical corticosteroid hypersensitivity. .A Reitamo S; Lauerma AI; Forstrom L. .I 200791 .U 90004282 .S Contact Dermatitis 9001; 21(3):166-71 .M Administration, Topical; Animal; Anti-Infective Agents, Local/*IM; Antibiotics/*IM; Antiprotozoal Agents/IM; Chlorhexidine/IM; Comparative Study; Dermatitis, Contact/*ET; Drug Hypersensitivity/*ET; Guinea Pigs; Proflavine/IM; Support, Non-U.S. Gov't; Xylenes/IM. .T Contact sensitivity to topical antimicrobials. (II). Sensitizing potentials of some topical antimicrobials. .P JOURNAL ARTICLE. .W A predictive study comparing the sensitizing potentials of some topical antimicrobials, using a modified Beuhler's technique, showed that over-the-counter (OTC) antimicrobials were more sensitizing than prescribed topical antibiotics. Among OTC antimicrobials, proflavine was the most potent sensitizer (4/10 guinea pigs); parachlorometaxylenol, benzalkonium chloride and propamidine isethionate moderate sensitizers (2/10 guinea pigs); iodine a weak sensitizer (1/10 guinea pigs); and chlorhexidine and cetrimide very weak sensitizers (0/10 guinea pigs). Among prescribed topical antibiotics, neomycin was a moderate sensitizer (2/10 guinea pigs); gentamycin and chloramphenicol weak sensitizers (1/10 guinea pigs); kanamycin, clioquinol, polymyxin B, bacitracin, tetracycline, sodium fusidate and fusidic acid very weak sensitizers (0/10 guinea pigs). There was good correlation between sensitizing potentials in animal studies and clinical experience of contact allergy to these topical antimicrobials. .A Goh CL. .I 200792 .U 90004283 .S Contact Dermatitis 9001; 21(3):172-8 .M Adolescence; Adult; Age Factors; Aged; Animal; Child; Erythema/*ET; Female; Fish Products/*AE; Human; Male; Middle Age; Occupational Diseases/*ET; Pruritus/*ET; Skin Tests; Time Factors; Urticaria/*ET. .T Skin irritancy from fish is related to its postmortem age. .P JOURNAL ARTICLE. .W Scratch tests with different fish products (fish juice from fillets, meat (fillet), skin, slime, juice from fish boxes and hold in the fishing boats, and entrails) were performed in 145 volunteers. All fish products were able to cause irritant skin reactions. Itching and erythema were the predominant symptoms and severe itch reactions occurred more often than severe erythema. The symptoms, in general, were mild to moderate compared to histamine. We found that the postmortem age of the fish was of great importance to the frequency and severity of the symptoms. Only the protein fraction of fish products caused symptoms. Our results are in accordance with the subjective complaints and clinical findings among workers in the fish processing industry. .A Halkier-Sorensen L; Thestrup-Pedersen K. .I 200793 .U 90004284 .S Contact Dermatitis 9001; 21(3):179-83 .M Adult; Aged; Cold; Erythema/ET; Female; Fish Products/*AE; Histamine/*IM; Human; Male; Middle Age; Occupational Diseases/*ET; Pruritus/*ET; Skin Temperature/*; Skin Tests; Urticaria/*ET. .T The relevance of low skin temperature inhibiting histamine-induced itch to the location of contact urticarial symptoms in the fish processing industry. .P JOURNAL ARTICLE. .W We have studied the influence of cold exposure on itch, erythema and wheal, in response to histamine scratch tests, in 14 volunteers. Cooling of the skin to less than 20 degrees C, by application of an ice cube for 30 min on the inside of the forearm, abolished itch and reduced erythema by approximately 50%, whereas the size of the wheal was unaffected by cooling. The observations bear significance for an explanation of the well-known observation that cold relieves itch. A normal itch response seems to require a continuous metabolic process in the skin, which is inhibited at temperatures less than 20 degrees C. The skin symptoms, itching and erythema, among workers in the fish processing industry are mainly localized to the forearms and backs of the hands, but only seldom to the fingers and palms, although they are in direct contact with fish products. Skin temperature measurements have shown that the temperature on the fingers and palms is less than 20 degrees C, while the temperature on the backs of the hands and forearms ranges from 25 to 30 degrees C. We therefore conclude that the skin temperature is an important factor for the location of skin symptoms among workers in the fish processing industry. .A Halkier-Sorensen L; Thestrup-Pedersen K. .I 200794 .U 90004285 .S Contact Dermatitis 9001; 21(3):184-8 .M Adult; Chromatography, High Pressure Liquid; Dermatitis, Contact/*ET; Female; Human; Male; Skin Tests/*; Sodium Dodecyl Sulfate/*AE/IM. .T Different skin irritation abilities of different qualities of sodium lauryl sulphate. .P JOURNAL ARTICLE. .W A marked variation in the concentration of sodium lauryl sulphate (SLS) used for irritant patch testing is found in the literature, but is hitherto unexplained. In the present study, 2 different qualities of SLS were tested clinically on healthy volunteers. The skin responses were evaluated by visual scoring as well as by non-invasive measurement of transepidermal water loss (TEWL), blood flow and oedema. A significant difference in the skin response to the 2 qualities was found both clinically and by non-invasive methods used for quantitation. 5 different qualities of SLS were investigated by high-performance liquid chromatography (HPLC). Marked discrepancies in the quantity of C12 carbon chains in the products were found, offering an explanation for the proven difference in the clinical response. It is concluded that only SLS qualities of high purity should be used for irritant patch testing, and that both the quality and the purity of SLS should be stated. .A Agner T; Serup J; Handlos V; Batsberg W. .I 200795 .U 90004286 .S Contact Dermatitis 9001; 21(3):189-93 .M Administration, Cutaneous; Animal; Dermatitis, Contact/*ET; Guinea Pigs; Pyridostigmine Bromide/*AE/IM; Sodium Dodecyl Sulfate/AE/IM; Support, U.S. Gov't, Non-P.H.S.. .T Allergic contact dermatitis potential of 3 pyridostigmine bromide transdermal drug delivery formulations. .P JOURNAL ARTICLE. .W Pyridostigmine bromide (PB) delivered transdermally may be a useful pretreatment for organophosphate poisoning. PB transdermal formulations were developed since this route has the potential to provide a more constant, prolonged and therapeutically-effective drug level in the body. Guinea pig skin sensitization studies, using a variation of the split adjuvant technique, were conducted with various PB transdermal formulations as part of a safety evaluation profile. 3 gel matrix formulations were tested. The 3 formulations contained 50% PB, 30% PB with 0.198% sodium lauryl sulfate (SLS) and 30% PB with 0.21% of a proprietary surfactant (PS), respectively. SLS and the proprietary surfactant were added to the formulations as dermal penetration enhancers. 9 groups of 10 animals were induced and challenged with 1 of the 3 PB or PB/surfactant formulations (3 groups per formulation). In addition, 2 groups of 10 animals were included in the study as positive controls that were induced and challenged with 2,4-dinitrochlorobenzene (DNCB). 44% of the animals responded positively at challenge to 50% PB. 80% of the animals responded positively at challenge to 30% PB/0.198% SLS and 82% of the animals had positive responses at challenge to 30% PB/0.21% PS. This study demonstrates that PB is a potential contact sensitizer that shows a potentiated response in the presence of surfactants. .A Harris GL; Maibach HI. .I 200796 .U 90004287 .S Contact Dermatitis 9001; 21(3):194-5 .M Adolescence; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Dermatitis, Contact/*ET/IM; Female; Human; Middle Age; Nickel/*AE/IM; Psoriasis/*ET. .T Non-occupational metal-related contact reactions in women with psoriasis. .P JOURNAL ARTICLE. .A Dave VK; Cross D. .I 200797 .U 90004288 .S Contact Dermatitis 9001; 21(3):195 .M Aged; Allergens; Butylated Hydroxytoluene/*AE; Case Report; Dermatitis, Contact/CO/*ET; Human; Leg Ulcer/*CO; Male. .T Allergic contact dermatitis from BHT in leg ulcer patients. .P JOURNAL ARTICLE. .A Dissanayake M; Powell SM. .I 200798 .U 90004289 .S Contact Dermatitis 9001; 21(3):196-7 .M Administration, Topical; Adult; Alopecia Areata/*TH; Case Report; Cyclobutanes/*AE; Cyclopropanes/*AE; Dermatitis, Contact/*ET; Dinitrochlorobenzene/*AE; Female; Human; Immunotherapy/*; Male; Urticaria/*CI. .T Contact urticaria during topical immunotherapy. .P JOURNAL ARTICLE. .A Tosti A; Guerra L; Bardazzi F. .I 200799 .U 90004290 .S Contact Dermatitis 9001; 21(3):197-8 .M Adult; Anaphylaxis/ET; Case Report; Dermatitis, Contact/*ET; Female; Human; Intraoperative Complications/*; Intubation, Intratracheal/AE; Nasal Septum/SU; Rubber/*AE; Skin Tests; Urticaria/*CI. .T Rubber latex allergy: unusual complication during surgery. .P JOURNAL ARTICLE. .A Zenarola P. .I 200800 .U 90004291 .S Contact Dermatitis 9001; 21(3):198-200 .M Dermatitis, Contact/*DI; Diagnosis, Differential; Fibrin/*ME; Fluoroimmunoassay; Human; Irritants/*. .T Differentiation of allergic from irritant contact dermatitis by dermal fibrin deposition patterns. .P JOURNAL ARTICLE. .A Beutner EH; Rudzki E; Chorzelski TP; Kowalewski C; Kumar V; Rebandel P. .I 200801 .U 90004292 .S Contact Dermatitis 9001; 21(3):200-1 .M Case Report; Dermatitis, Contact/*ET; Female; Human; Middle Age; Photosensitivity Disorders/*ET; Trees/*. .T Contact and photocontact dermatitis from Ruta chalepensis. .P JOURNAL ARTICLE. .A Goncalo S; Correia C; Couto JS; Goncalo M. .I 200802 .U 90004293 .S Contact Dermatitis 9001; 21(3):201-2 .M Adult; Case Report; Catechols/*AE; Dermatitis, Contact/*ET; Female; Human; Hypersensitivity; Occupational Dermatitis/*CI. .T Occupational contact dermatitis from pyrocatechol. .P JOURNAL ARTICLE. .A Morelli R; Piancastelli E; Lanzarini M; Restani S. .I 200803 .U 90004294 .S Contact Dermatitis 9001; 21(3):202-3 .M Air Pollutants, Occupational/*PO; Case Report; Dermatitis, Contact/*ET; Human; Hypersensitivity; Male; Middle Age; Paint/PO; Triazines/*AE. .T Airborne contact dermatitis due to triglycidylisocyanurate. .P JOURNAL ARTICLE. .A Dooms-Goossens A; Bedert R; Vandaele M; Degreef H. .I 200804 .U 90004295 .S Contact Dermatitis 9001; 21(3):204 .M Adult; Case Report; Female; Human; Hypersensitivity; Nickel/*AE; Stomatitis/*; Stomatitis, Denture/*. .T Contact stomatitis from a dental prosthesis. .P JOURNAL ARTICLE. .A Romaguera C; Vilaplana J; Grimalt F. .I 200805 .U 90004296 .S Contact Dermatitis 9001; 21(3):204-5 .M Case Report; Chronic Disease; Dental Implantation/*; Female; Human; Middle Age; Nickel/*AE; Skin Tests; Urticaria/*CI. .T Chronic urticaria after implantation of 2 nickel-containing dental prostheses in a nickel-allergic patient. .P JOURNAL ARTICLE. .A Espana A; Alonso ML; Soria C; Guimaraens D; Ledo A. .I 200806 .U 90004313 .S Crit Care Med 9001; 17(10):1010-4 .M Aged; Amino Acids/BL/*ME; Comparative Study; Dialysis Solutions/ME; Female; Hemofiltration/*; Human; Kidney Failure, Acute/ME; Male; Middle Age; Prospective Studies; Respiratory Insufficiency/ME; Septicemia/*ME; Shock, Cardiogenic/*ME; Statistics. .T Amino acid losses during continuous high-flux hemofiltration in the critically ill patient. .P JOURNAL ARTICLE. .W Total amino acid losses were measured daily in the ultrafiltrate collected from eight patients with acute renal failure treated by continuous high-flux venovenous hemofiltration. All patients had type-1 respiratory failure and required mechanical ventilation. Four patients also suffered cardiogenic shock and were dependent on two or more inotropic drugs; the other four had Escherichia coli septicemia. All patients received identical daily parenteral nutrition as a continuous infusion. The overall mean serum amino acid values were greater in the group with cardiogenic shock (180 +/- 36 [SEM] mumol/L) compared to those with septicemia (131 +/- 26 mumol/L; p less than .05). The daily ultrafiltrate losses of amino acids were also greater, 4.2 +/- 0.7 mmol/24 h (1.1 g N) compared to 2.1 +/- 0.3 mmol/24 h (0.6 g N, p less than .05). For all patients there was a positive correlation between the serum amino acid value and ultrafiltrate loss (r = .84, p less than .001). However, the slopes of the regression curves for the two groups differed (p less than .001), suggesting that for the same plasma value the ultrafiltrate loss was greater for those patients with cardiogenic shock. .A Davenport A; Roberts NB. .I 200807 .U 90004314 .S Crit Care Med 9001; 17(10):1015-9 .M Animal; B-Lymphocytes/*IM/SE; Enzyme-Linked Immunosorbent Assay; Hemorrhage/IM/PA/*PP; Immunoglobulin Isotypes/BI; Immunoglobulins/BI; Male; Mice; Spleen/CY; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Hemorrhage in mice induces alterations in immunoglobulin-secreting B cells. .P JOURNAL ARTICLE. .W Infections remain the major cause of late morbidity and mortality after hemorrhage, trauma, and burns. Abnormalities in immune response appear to play a major role in the increased susceptibility to infection in this setting. In the present study, the effect of hemorrhage on the numbers of splenic B cells and isotype-specific immunoglobulin(Ig)-secreting cells in mice was investigated. No changes in the total number of splenocytes or of splenic B cells were found after hemorrhage. Decreases of greater than 40% in the total number of Ig-producing cells as well as in the numbers of B cells secreting IgM, IgA, and IgG2b were found during the period of 2 to 96 h posthemorrhage. Subsequent increases in the numbers of cells secreting IgA, IgG1, IgG2a, and IgG3 were present 96 to 144 h after hemorrhage. Total serum Ig levels fell by approximately 40% 3 days after hemorrhage, and then returned to normal within 5 days posthemorrhage. These results demonstrate that hemorrhage produces marked alteration in B-cell populations and serum Ig levels. .A Abraham E; Freitas AA. .I 200808 .U 90004316 .S Crit Care Med 9001; 17(10):1025-30 .M Animal; Burns/*ME/PP; Cardiac Output; Female; Hemodynamics; Lipid Peroxidation/*; Lipid Peroxides/ME; Oxygen/*BL; Oxygen Consumption/*; Sheep; Support, U.S. Gov't, P.H.S.. .T Effect of increasing oxygen delivery postburn on oxygen consumption and oxidant-induced lipid peroxidation in the adult sheep. .P JOURNAL ARTICLE. .W We studied the relationship between oxygen delivery (DO2) and oxygen consumption (VO2) in the early post-burn period. Unanesthetized sheep with a 15% total body surface (TBS) third-degree burn were resuscitated back to baseline VO2 and vascular pressures. DO2 was adjusted further by infusion and removal of whole blood. The response was compared to the same maneuver in nonburned sheep. We found that increasing DO2 after burns resulted in a 32% increase in VO2, while the same maneuver in controls produced no change in VO2. We then determined whether the increase in VO2, caused by volume loading, resulted in a further increase in postburn oxidant release and lipid peroxidation measured as conjugated dienes. Plasma conjugated dienes increased significantly and equally by 30% in burns maintained at baseline VO2 vs. the increased VO2. Therefore, the increased oxygen used is not simply resulting in further oxidant damage. VO2 was maintained equally in both burned animals and controls with a decrease in DO2 by increased oxygen extraction from Hgb. We conclude that standard burn resuscitation does not restore adequate DO2 for oxygen demands. The 30% increase in VO2 achieved by increasing DO2 does not lead to a further release of oxidants from burn tissue and is therefore potentially beneficial for cell function. .A Demling RH; Lalonde C; Fogt F; Zhu DG; Liu YP. .I 200809 .U 90004317 .S Crit Care Med 9001; 17(10):1031-5 .M Animal; Biological Transport; Blood Volume; Cardiac Output; Comparative Study; Dextrans/*TU; Fluid Therapy/*; Hemodilution; Hemodynamics/*; Hydroxyethyl Starch/*TU; Isotonic Solutions/*TU; Models, Biological; Oxygen/*BL; Oxygen Consumption; Shock, Hemorrhagic/*PP/TH; Starch/*AA; Support, Non-U.S. Gov't; Swine. .T Cardiorespiratory function after replacement of blood loss with hydroxyethyl starch 120, dextran-70, and Ringer's acetate in pigs. .P JOURNAL ARTICLE. .W The small intestines of 20 anesthetized pigs weighing 12 to 17 kg were exteriorized in a saline-moistened gauze in order to simulate an intra-abdominal operation. During a 2-h period, 4% of the animals' body weight was bled through an arterial cannula in six increments and replaced immediately with one of the following fluids: a) a new medium-MW hydroxyethyl starch (HES 120), b) dextran-70 (DEX), or c) Ringer's acetate (RA). The amount of fluid infused was equal to the amount of blood withdrawn in the plasma substitute groups, but was increased four-fold in the RA group. Five nonbled pigs served as controls. No statistically significant changes occurred within the control group in any of the variables measured. One animal died of hypovolemic shock 3 h after RA administration. Bleeding and fluid infusion caused a 41% and 44% reduction in Hgb in the HES and DEX groups, respectively, while RA caused only a 25% reduction. A prompt increase in cardiac output was detected in animals receiving colloids (52% with HES), and cardiac output was maintained above initial values during the entire 5-h follow-up period. In the RA group, no increase in cardiac output occurred during fluid administration; during the follow-up period, cardiac output decreased consistently. Similarly, stroke volume and arterial pressures were best maintained with HES, but decreased after RA. Oxygen consumption and delivery were highest after HES and lowest in the RA group, where arteriovenous oxygen difference increased throughout the study. We conclude that both colloid solutions were superior to RA, which did not prevent hypovolemia or maintain adequate oxygen transport. .A Linko K; Makelainen A. .I 200810 .U 90004318 .S Crit Care Med 9001; 17(10):1036-40 .M Animal; Blood Gas Analysis; Dogs; Endotoxins/AD; Hemodynamics/DE; Hydrogen-Ion Concentration; Injections, Intravenous; Oxygen Consumption/DE; Shock, Septic/*DT/ME/PP; Thiamine Pyrophosphate/*TU; Time Factors. .T Effect of cocarboxylase in dogs subjected to experimental septic shock. .P JOURNAL ARTICLE. .W We examined the effects of cocarboxylase treatment on both the hemodynamic variables and metabolic function during endotoxic shock in dogs. Cocarboxylase inhibited deterioration in metabolic function as reflected by improved pH and base excess as well as maintenance of normal oxygen consumption. Significant improvements in mean arterial pressure and cardiac index were also seen. Cocarboxylase is a major coenzyme of mitochondrial pyruvate dehydrogenase and may exert its beneficial effects via this complex. .A Lindenbaum GA; Larrieu AJ; Carroll SF; Kapusnick RA. .I 200811 .U 90004320 .S Crit Care Med 9001; 17(10):1048-51 .M Animal; Blood Coagulation Tests/*MT/SN; Blood Volume; Extracorporeal Membrane Oxygenation/*; Heparin/*AD; Regression Analysis; Reproducibility of Results; Sheep; Time Factors. .T Procedural variables which affect activated clotting time test results during extracorporeal membrane oxygenation therapy. .P JOURNAL ARTICLE. .W Hemorrhage secondary to heparin therapy is one of the most serious risks of extracorporeal membrane oxygenation (ECMO). This study determined those variables which affect the precision of activated clotting time (ACT) measurements used to monitor heparin therapy. Heparin therapy of eight neonatal lambs was monitored during ECMO with two Hemochron 400 machines to determine the effects of intermachine variability, test volume, speed and direction of agitation, and interpersonnel variability on ACT values. Test volume (0.25 vs. 0.4 ml) and agitation speed (2 shakes/sec vs. one shake/sec) resulted in significantly different ACT values (p less than .05). The mean matched ACT values determined from different agitation directions (vertical vs. horizontal) or the use of a stepper pipette to measure test volume vs. visual estimation of test volume were not significantly different. Variability in ACT test results is significantly increased by variations in test volume or agitation (speed and direction), intermachine variability, and by interpersonnel technique. These variables should be considered when devising protocols for ACT monitoring and management of heparin therapy. .A Uden DL; Payne NR; Kriesmer P; Cipolle RJ. .I 200812 .U 90004321 .S Crit Care Med 9001; 17(10):1052-6 .M Adult; Aged; Aged, 80 and over; Coma/TH; Female; Head and Neck Neoplasms/TH; Human; Male; Middle Age; Pneumonia/TH; Punctures; Tracheostomy/AE/IS/*MT. .T Percutaneous tracheostomy--a new method. .P JOURNAL ARTICLE. .W A rapid method of definitive low tracheostomy utilizing an original instrument kit and percutaneous approach is described. Through a horizontal, shallow (1.5-cm) skin incision in the neck, a 12-ga needle is introduced into the tracheal lumen. A flexible metal guidewire is gently introduced through the needle, which is then removed. A specially designed percutaneous tracheostomy tool slides over the guidewire into the trachea; by squeezing its handles, the intercartilaginous space is enlarged, securing the placement of a cuffed tracheal cannula. After extensive and successful investigation in both cadaver and animal trials, the procedure was carried out in 80 patients who had a variety of underlying diseases, without serious complications. Of these 80 patients, 33 required airway control after neurosurgical interventions or after severe head trauma, 23 had percutaneous tracheostomy performed before radical excision for head and neck cancer, and the remaining 24 suffered from severe cardiorespiratory problems. Twenty-nine procedures were performed in the operating theater, and 51 procedures were carried out at the patient's bedside in the ICU, ED, or in the ward. There was no infection at the stoma site, and late healing was remarkable. It should be strongly emphasized that in the majority of our patients the procedure was carried out safely at the bedside. This resolved the logistic problem of moving very sick ICU patients (who are sometimes on high PEEP levels) to the OR. Although our experience is totally restricted to elective situations, we do postulate that it could be as effective in a variety of urgent situations. .A Schachner A; Ovil Y; Sidi J; Rogev M; Heilbronn Y; Levy MJ. .I 200813 .U 90004322 .S Crit Care Med 9001; 17(10):1057-9 .M Animal; Autopsy; Blood Pressure; Dogs; Emergencies; Heart Rate; Human; Lung/*PP; Male; Shock, Hemorrhagic/PP/*SU; Thoracotomy/*/MT; Ventilators, Mechanical/*. .T Selective right-lung ventilation during emergency department thoracotomy. .P JOURNAL ARTICLE. .W Surgeons are occasionally called on to manage patients with penetrating cardiac injuries who arrive at the ED in extremis. Immediate thoracotomy in the ED is associated with good resuscitative results in a select group of such patients, but cardiorrhaphy is often impeded by frequent inflations of the left lung during resuscitation. We investigated a technique for selective right-lung ventilation using a standard single-lumen endotracheal tube in cadaver and animal models. This technique is easily applicable, provides adequate oxygenation and ventilation for up to 60 min, and expedites cardiorrhaphy in the ED. .A Lui RC; Johnson FE. .I 200814 .U 90004324 .S Crit Care Med 9001; 17(10):1062-7 .M Disaster Planning/*MT; Emergency Medical Services/*OG; France; Human; Regional Medical Programs; Trauma Severity Indices; Triage; Violence; Wounds and Injuries/CL/*TH. .T Emergency medical services for treatment of mass casualties. .P JOURNAL ARTICLE. .W The French emergency medical system (EMS) is the Service d'Aide Medicale Urgente (SAMU). In case of mass casualties, involving 100 simultaneous victims, SAMU has developed a disaster plan, "The White Plan." This plan is closely correlated to the Red Plan of the Fire Department, to provide advanced life support (ALS) at the incident site, followed in a continuum by medical transport and hospitalization in the appropriate services. To obtain the best chance of survival and recovery, there must be optimal coordination among all rescuers. This objective was approached by adopting a formal protocol designed for each city. In France, the medical organization for the treatment of casualties is operated by anesthesiologists who are qualified to perform ALS, preanesthetic evaluation en route, anesthesia for the multitrauma patient, and postanesthetic resuscitation in a continuum from the accident scene to the ICU. .A Barrier G. .I 200815 .U 90004325 .S Crit Care Med 9001; 17(10):1068-72 .M Adult; Age Factors; Aged; Anxiety/PX; Communication; Consumer Satisfaction/*; Emotions; Female; Human; Male; Middle Age; Retrospective Studies; Statistics; Support, Non-U.S. Gov't; Ventilators, Mechanical/*. .T Assessment of patients' experience of discomforts during respirator therapy. .P JOURNAL ARTICLE. .W Patients (n = 158) who had been respirator-treated and who could remember the treatment were retrospectively (after greater than 2 months) interviewed about their experiences. Of all patients, 47% had felt anxiety and/or fear during the treatment. These feelings were intimately related to the experience of agony/panic (p less than .001) and insecurity (p less than .001). Inability to talk and communicate was found to be the dominating reason (p less than .001) for evoking such feelings and also made it difficult for the patients to sleep and rest (p less than .05); no correlation to pain was found. Difficulties to synchronize with the respirator in connection with suctioning also caused feelings of anxiety/fear (p less than .01), agony/panic (p less than .01), and insecurity (p less than .001). Even as long as 4 yr after respirator treatment, most patients (90%) who remember the treatment still recall the situation as unpleasant and stress-evoking. The isolation due to communication difficulties was a greater problem than direct airway-related nursing care activities. This relationship between communication difficulties and severe emotional reactions should be considered in the nursing care of respirator-treated patients. .A Bergbom-Engberg I; Haljamae H. .I 200816 .U 90004326 .S Crit Care Med 9001; 17(10):1073-4 .M Acute Disease; Adult; Case Report; Cocaine/*; Human; Male; Rhabdomyolysis/*ET; Substance Abuse/*CO. .T Crack-induced rhabdomyolysis. .P JOURNAL ARTICLE. .A Steingrub JS; Sweet S; Teres D. .I 200817 .U 90004327 .S Crit Care Med 9001; 17(10):1075-6 .M Acetylcholinesterase/BL; Adult; Case Report; Gagging/PH; Human; Male; Organophosphorus Compounds/*PO; Syndrome; Ventilator Weaning/*. .T Difficulty in weaning from respiratory support in a patient with the intermediate syndrome of organophosphate poisoning. .P JOURNAL ARTICLE. .A Routier RJ; Lipman J; Brown K. .I 200818 .U 90004328 .S Crit Care Med 9001; 17(10):1077 .M Burns/*PP; Human; Resuscitation/*MT; Shock, Traumatic/PP. .T Toward a re-evaluation of burn resuscitation [editorial] .P EDITORIAL. .A Waxman K. .I 200819 .U 90004329 .S Crit Care Med 9001; 17(10):1078-80 .M Fluid Therapy/*; Human; Resuscitation/*; Shock/*TH. .T Fluid resuscitation of shock: current controversies [editorial] .P EDITORIAL. .A Dawidson I. .I 200820 .U 90004330 .S Crit Care Med 9001; 17(10):1081 .M Abortion, Missed/TH; Adult; Amphotericin B/*AE; Blood Transfusion/*; Case Report; Dilatation and Curettage/AE; Female; Human; Leukocytes/*TR; Pregnancy; Respiratory Distress Syndrome, Adult/*CI. .T Pulmonary reactions associated with the combined use of amphotericin B and leukocyte transfusions [letter] .P LETTER. .A Krimerman S; Potasman I; Barak A. .I 200821 .U 90004331 .S Crit Care Med 9001; 17(10):1081-2 .M Aged; Aged, 80 and over; Case Report; Heart Catheterization/*AE; Human; Male; Pulmonary Artery/*. .T An unusual case of pulmonary artery catheter knotting during withdrawal [letter] .P LETTER. .A Agarwal NN; Giesswein P; Leverett L; Gracey J; Hess D. .I 200822 .U 90004332 .S Crit Care Med 9001; 17(10):1082-3 .M Administration, Intranasal; Child, Preschool; Human; Hypertension/*DT; Male; Nifedipine/*AD/TU. .T Intranasal administration of nifedipine for treatment of hypertension [letter; comment] .P COMMENT; LETTER. .A Miller DR; Teasdale SJ; Mullen JM. .I 200823 .U 90004334 .S Crit Care Med 9001; 17(10):1084-5 .M Human; Hypotension/DT; Norepinephrine/TU; Prospective Studies; Shock, Septic/*PP. .T Reversal of intractable septic shock [letter; comment] .P COMMENT; LETTER. .A Bollaert PE; Bauer P; Audibert G; Lambert H; Larcan A. .I 200824 .U 90004335 .S Crit Care Med 9001; 17(10):1085-6 .M Ethics, Medical/*; Human; Life Support Care/*LJ; Philosophy, Medical/*; Resuscitation/*. .T Philosophical, ethical, and legal aspects of resuscitation medicine [letter; comment] .P COMMENT; LETTER. .A Gilbert J. .I 200825 .U 90004336 .S Crit Care Med 9001; 17(10):1086-7 .M Blood Transfusion/*IS; Equipment Design; Human. .T Simple pressuring plate--RIPPS [letter] .P LETTER. .A Watanabe H; Kanaoka K; Miyazawa K; Sumita S; Namiki A. .I 200826 .U 90004337 .S Crit Care Med 9001; 17(10):975-8 .M Adolescence; Adult; Aged; Child; Child, Preschool; Female; Human; Infant; Infant, Newborn; Interleukin-1/*BL; Male; Middle Age; Septicemia/*BL; Shock, Septic/*BL/MO; Support, Non-U.S. Gov't; Tumor Necrosis Factor/*AN. .T Tumor necrosis factor and interleukin-1 serum levels during severe sepsis in humans. .P JOURNAL ARTICLE. .W In a study of serum levels of tumor necrosis factor (TNF alpha) and interleukin-1 beta (IL-1 beta) in patients developing sepsis in the ICU, high TNF alpha levels were found in patients with septic shock. Normal values are 75 +/- 15 pg/ml; in these patients, TNF alpha serum level ranged from 100 to 5000 pg/ml with a mean of 701 +/- 339 pg/ml and a median of 250 pg/ml. There was a correlation between TNF alpha level and sepsis severity score as well as with mortality. In contrast, IL-1 beta serum levels were only slightly increased and were not correlated with severity or mortality. .A Damas P; Reuter A; Gysen P; Demonty J; Lamy M; Franchimont P. .I 200827 .U 90004338 .S Crit Care Med 9001; 17(10):979-83 .M Acute Disease; Adult; Aged; Cardiac Output/*; Cardiography, Impedance; Heart/*PH; Hemorrhage/*PP; Human; Hypotension, Orthostatic/PP; Leg/PH; Male; Middle Age; Posture; Stroke Volume/*. .T Changes in cardiac output after acute blood loss and position change in man [see comments] .P JOURNAL ARTICLE. .W Thoracic bioimpedance cardiac output (Qtbi) was measured at 1-min intervals in 27 volunteers before, during, and after withdrawing 500 ml (3.7 to 8.5 ml/kg; mean 5.8) of blood. The effects of passive leg raising (PLR) and standing on Qtbi were measured before and after blood withdrawal. Arterial oxygen saturation (SaO2), transcutaneous oxygen tension (PtcO2), mean arterial BP (MAP), and heart rate (HR) were also measured before and after blood withdrawal. Thoracic bioimpedance cardiac index (CI) decreased 18% (0.8 +/- 0.1 L/min.m2, p less than .0001) and stroke volume index (SI) decreased 22% (14.8 +/- 2.7 ml/beat.m2, p less than .0001) after blood withdrawal. HR, MAP, SaO2, and PtcO2 were not significantly different after blood withdrawal. Before blood withdrawal PLR increased CI 6.8% (0.3 +/- 0.1 L/min.m2, p less than .0001); after blood withdrawal PLR increased CI 11.1% (0.4 +/- 0.1 L/min.m2, p less than .0001). PLR can increase stroke volume and cardiac output in hypovolemic humans. .A Wong DH; O'Connor D; Tremper KK; Zaccari J; Thompson P; Hill D. .I 200828 .U 90004339 .S Crit Care Med 9001; 17(10):984-8 .M Adolescence; Adult; Bacterial Infections/MO; Catheterization, Central Venous/*AE; Catheters, Indwelling; Child; Child, Preschool; Critical Care/*; Embolism/MO; Hemorrhage/MO; Human; Infant; Infant, Newborn; Intensive Care Units, Pediatric; Survival Analysis; Time Factors; Veins/IN. .T Percutaneous central venous catheterization in a pediatric intensive care unit: a survival analysis of complications [see comments] .P JOURNAL ARTICLE. .W We investigated the relationship between the duration of percutaneous central venous catheterization and the occurrence of catheter-related complications in critically ill children by survival analysis techniques. Data were collected prospectively and analyzed for infectious and noninfectious complications from 379 pediatric patients in whom central venous catheters had been placed in the pediatric ICU over a 45-month period. Cumulative survival rate analysis revealed a linear decrease in the number of complication-free catheters with time. The median duration of complication-free catheter survival was projected to be 23.3 days. The risk of catheter complication did not increase with increasing daily duration of catheter use as demonstrated by probability density function: catheter complication rates were similar on the first day after insertion (1.06 +/- 0.5%), the seventh day (4.27 +/- 1.6%), and the 24th day (2.48 +/- 2.4%). Therefore, in this population, routine catheter replacement would not be expected to lower the incidence of catheter-related complications, but may unnecessarily increase the number of insertion-related complications. .A Stenzel JP; Green TP; Fuhrman BP; Carlson PE; Marchessault RP. .I 200829 .U 90004341 .S Crit Care Med 9001; 17(10):993-5 .M Adolescence; Age Factors; Body Temperature; Child; Child, Preschool; Female; Florida; Human; Infant; Male; Near Drowning/*; Nervous System/*PP; Pain/PP; Prognosis; Resuscitation/MT/*UT; Retrospective Studies; Sex Factors. .T Childhood near-drowning: is cardiopulmonary resuscitation always indicated? .P JOURNAL ARTICLE. .W The case histories of 93 consecutive pediatric near-drowning victims admitted to All Children's Hospital from 1983 to 1987 were retrospectively reviewed for patient status on ED arrival and eventual outcome. Age, sex, length of submersion, core temperature, pHa, absence of spontaneous respiration, lack of response to pain, and pupillary nonreactivity were all found to be unreliable predictors of outcome. Of those who received CPR, 68% went on to intact survival. The use of cardiotonic medicines to establish a perfusing cardiac rhythm in the initial resuscitation was associated with an eventual outcome of severe neurologic damage or death in all instances. The decision to use cardiotonic medicines in the resuscitation of pediatric near-drowning victims should be weighed carefully against their ultimate chances of intact survival. .A Nichter MA; Everett PB. .I 200830 .U 90004342 .S Crit Care Med 9001; 17(10):996-8 .M Adult; Aged; Blood Pressure; Colloids; Critical Care/*; Female; Gelatin/*AD; Heart Arrest/PP; Hemodynamics/*; Human; Infusions, Intravenous; Male; Middle Age; Oxygen Consumption/*; Plasma Substitutes/*; Prospective Studies; Shock/PP; Stroke Volume; Succinates/*AD. .T Hemodynamic and oxygen transport response to modified fluid gelatin in critically ill patients. .P JOURNAL ARTICLE. .W The hemodynamic and oxygen transport effects of the rapid infusion of 500 ml of modified fluid gelatin, an artificial colloid widely used in Europe, were studied in a group of critically ill patients suffering from cardiovascular instability. Oxygen consumption tended to increase. There were no significant changes in heart rate, shunt fraction, or systemic vascular resistance index. There were significant increases in mean arterial pressure, pulmonary artery wedge pressure, stroke index, cardiac index, and oxygen delivery. There were significant decreases in Hgb concentration and arterial oxygen content. The overall circulatory effects of modified fluid gelatin are beneficial. .A Edwards JD; Nightingale P; Wilkins RG; Faragher EB. .I 200831 .U 90004343 .S Crit Care Med 9001; 17(10):999-1003 .M Adult; Aged; Dopamine/*AA/AD/AE/TU; Dose-Response Relationship, Drug; Female; Hemodynamics/DE; Human; Infusions, Intravenous; Male; Middle Age; Oliguria/PP/UR; Shock, Septic/*DT/PP/UR; Time Factors. .T Use of dopexamine hydrochloride in patients with septic shock. .P JOURNAL ARTICLE. .W The short and long-term hemodynamic effects of iv dopexamine hydrochloride (DPX) were studied in ten patients with septic shock. In the short-term study, a dose-dependent increase in cardiac index and heart rate, and a dose-dependent decrease in systemic vascular resistance were demonstrated. These effects diminished gradually during the long-term study, suggesting a problem of tolerance. Although the administration of DPX during septic shock appeared to be relatively safe, its hemodynamic effects suggest that it may be more indicated in selected patients with a low cardiac output. .A Colardyn FC; Vandenbogaerde JF; Vogelaers DP; Verbeke JH. .I 200832 .U 90004344 .S Crit Care Med 9001; 17(11):1091-7 .M Comparative Study; Decision Making, Computer-Assisted/*; False Positive Reactions; Female; Human; Intensive Care Units; Life Support Care/*; Male; Middle Age; Multiple Organ Failure/MO/*PP; Outcome and Process Assessment (Health Care); Prognosis; Severity of Illness Index/*. .T Accuracy of decisions to withdraw therapy in critically ill patients: clinical judgment versus a computer model. .P JOURNAL ARTICLE. .W Two clinicians and the nursing sisters working in the ICU evaluated the chance of survival of ICU patients every day. Patients were assessed either as "outcome unknown or will die." These predictions were compared with those made by computerized trend analysis of daily acute physiology and chronic health evaluation (APACHE II) scores corrected for the presence and duration of major organ system failure. The predictions were not acted upon during the study. Comparing the predictions with actual hospital outcome, the doctors and nurses had a false-positive diagnosis rate for dying of between 7.7% and 16.7%, while there were no false predictions by the computer model. The patients predicted to die by the doctors and nurses were not completely identical to those predicted by the computer. Predictions of doctors and nurses that were confirmed by the computer had a sensitivity of 20% and no false predictions of death. .A Chang RW; Lee B; Jacobs S; Lee B. .I 200833 .U 90004345 .S Crit Care Med 9001; 17(11):1098-103 .M Adult; Aged; Critical Care/*MT; Dobutamine/*TU; Dopamine/*TU; Female; Hemodynamics/*DE; Human; Male; Middle Age; Norepinephrine/*TU; Oxygen Consumption; Plasma Substitutes/*TU; Prospective Studies; Shock, Septic/MO/*TH. .T Use of survivors' cardiorespiratory values as therapeutic goals in septic shock [see comments] .P JOURNAL ARTICLE. .W The responses to therapy of 29 patients in septic shock are described. Patients received controlled plasma volume expansion followed by infusions of norepinephrine, dobutamine, and dopamine to achieve appropriate therapeutic goals. Increases in oxygen delivery (Do2) from 605 +/- 40 (SEM) to 843 +/- 27 ml/min-m2 (p less than .001) were associated with increases in oxygen consumption (Vo2) from 130 +/- 6.8 to 169 +/- 6.2 ml/min.m2 (p less than .001). The overall hospital survival rate was 52%. We suggest that the rational use of adrenergic agents and the achievement of appropriate physiologic end-points for therapy not only result in the reversal of hypotension, but also maintain or increase Do2 and Vo2, and may improve survival. .A Edwards JD; Brown GC; Nightingale P; Slater RM; Faragher EB. .I 200834 .U 90004346 .S Crit Care Med 9001; 17(11):1104-7 .M Adult; Aged; Critical Care; Drug Evaluation; Female; Hemodynamics/DE; Human; Kidney/*DE; Lactates/*BL; Male; Middle Age; Norepinephrine/*TU; Retrospective Studies; Shock, Septic/BL/*DT/MO. .T Effects of norepinephrine on renal function in septic patients with normal and elevated serum lactate levels. .P JOURNAL ARTICLE. .W Effects of iv norepinephrine (NE) on renal function were investigated retrospectively in 15 patients with hyperdynamic septic shock. All patients had either a low systolic BP less than 80 mm Hg, and/or oliguria less than 0.5 ml/kg-h. We examined their serum creatinine level (SCr), daily urine flow (UF), 24-h creatinine clearance (Ccr), and hemodynamic indices before and during NE infusion. Before NE administration, the patients were divided into those with with a serum lactate level (Lac) less than 20 mg/dl (group A, n = 9) and greater than 20 mg/dl (group B, n = 6). NE was infused continuously at rates between 0.05 and 0.24 microgram/kg.min which increased systolic BP by greater than or equal to 20 mm Hg. Cardiac index was not significantly changed in either group. In group A, NE increased both UF (p less than .05), and systemic vascular resistance index (SVRI) (p less than .01), but did not affect Ccr. In group B, NE did not increase UF nor SVRI, and decreased Ccr significantly (p less than .05). It is concluded that NE increased UF and SVRI only when Lac was in normal range; otherwise, NE reduced renal function. Thus, when administering NE to increase UF, both Lac and renal function should be monitored carefully. .A Fukuoka T; Nishimura M; Imanaka H; Taenaka N; Yoshiya I; Takezawa J. .I 200835 .U 90004348 .S Crit Care Med 9001; 17(11):1115-20 .M Acidosis, Respiratory/CO; Aged; Electrolytes/BL; Female; Human; Hydrogen-Ion Concentration; Intensive Care Units; Lung Diseases, Obstructive/BL/CO/*TH; Lung Volume Measurements; Male; Middle Age; Phosphates/*BL/UR; Prospective Studies; Respiration, Artificial/*AE; Respiratory Insufficiency/BL/CO/*TH. .T Hypophosphatemia induced by mechanical ventilation in patients with chronic obstructive pulmonary disease. .P JOURNAL ARTICLE. .W The aim of this study was to assess prospectively the variations of serum phosphorus concentration (P) after onset of mechanical ventilation (MV) in patients with chronic obstructive pulmonary disease (COPD) and acute respiratory acidosis. In 14 COPD patients, we measured P, PaCO2, and pH, immediately before MV (H0), then one hour (H1), 4 (H4), 7 (H7), 12 (H12), and 24 h (H24) after starting MV. P at H0 was in or above the normal range in ten patients and below normal range in four patients. P decreased significantly (p less than .001) after MV at H1, H4, H7, H12, and H24. Hypophosphatemia was present in all patients after MV, but was severe (p less than .3 mmol/L) in only two patients. There was a significant correlation (r = .56 p less than .01) between the decrease of P and the increase of pH after MV. Hypophosphatemia was a constant and early finding after institution of MV in COPD patients and was presumably related to an intracellular shift of P secondary to the correction of respiratory acidosis. .A Laaban JP; Grateau G; Psychoyos I; Laromiguiere M; Vuong TK; Rochemaure J. .I 200836 .U 90004349 .S Crit Care Med 9001; 17(11):1121-8 .M Hemodynamics; Human; Infection/PP; Prognosis; Pulmonary Gas Exchange; Respiratory Distress Syndrome, Adult/CO/MO/*PP; Support, Non-U.S. Gov't; Wounds and Injuries/CO/*PP. .T Respiratory index/pulmonary shunt relationship: quantification of severity and prognosis in the post-traumatic adult respiratory distress syndrome. .P JOURNAL ARTICLE. .W The relationship between the respiratory index (RI = alveolar-arterial oxygen gradient [P(A-a)O2] normalized by PaO2) and the pulmonary shunt (Qsp/Qt) has been examined in 929 studies from 240 critically ill post-traumatic patients. Of these, 88 patients (443 studies) were individuals who developed post-traumatic adult respiratory distress syndrome (ARDS) and 152 were patients (486 studies) who did not develop ARDS. This study demonstrates that the RI to Qsp/Qt [RI/(Qsp/Qt)] relationship was significantly (p less than .0001) increased in patients who developed fatal ARDS compared with those who did not develop ARDS, or with those whose ARDS resolved. Because of the increased oxygen consumption (VO2) in ARDS patients in association with their severe limitations in gas exchange (RI) and increased Qsp/Qt, surviving ARDS patients had a significant increase in the cardiac index which resulted in a higher oxygen delivery to VO2 ratio. ARDS patients showed significant (p less than .0001) evidence of increased pulmonary vascular tone, correlated with the increase in the RI/(Qsp/Qt) relationship. In addition, those patients with high RI/(Qsp/Qt) also had increased right ventricular (RVSW) to left ventricular work (LVSW) ratios which were shown to be a direct function of the rise in RI. This increase in both RVSW/LVSW and RI/(Qsp/Qt) ratios was significantly (p less than .0001) correlated with an increased mortality. Thus, the RI/(Qsp/Qt) relationship, which can be obtained from arterial and mixed venous blood gases and saturations only, can be used to predict the severity of the ARDS process as well as important pulmonary vascular and right ventricular overload consequences. .A Laghi F; Siegel JH; Rivkind AI; Chiarla C; DeGaetano A; Blevins S; Stoklosa JC; Borg UR; Belzberg H. .I 200837 .U 90004351 .S Crit Care Med 9001; 17(11):1143-5 .M Blood Specimen Collection; Blood Transfusion; Bloodletting/*AE; Diagnostic Tests, Routine/*MT; Hemorrhage/*ET; Human; Intensive Care Units; Prospective Studies. .T Effective measures for reducing blood loss from diagnostic laboratory tests in intensive care unit patients. .P JOURNAL ARTICLE. .W We studied ICU patient blood loss as a result of diagnostic testing (DBL) and the effect of two measures to reduce it. A policy of using small volumes (pediatric phlebotomy tubes, reduced syringe volumes) for the most frequent laboratory tests was implemented in our medical ICU. We prospectively studied 151 patients admitted during two consecutive 10-wk periods. During period 2, DBL was displayed on each ICU flow sheet. The DBL/day (43.6 +/- 3 [SEM] ml) was significantly lower (62.6 +/- 4 ml) than it would have been if standard volume tubes had been used. This represented an average savings of 33%. During period 1 (n = 81), eight (10%) patients with no diagnosis involving blood loss had a decrease in Hct and received transfusion. DBL was significantly higher (316 +/- 81 vs. 168 +/- 18 ml, p less than .001) for these patients and represented an average of 17% of transfusion requirements. During period 2 (n = 70), such transfusion requirements were significantly reduced (only one of 70, p less than .001), as were tests ordered/day (7.8 +/- 0.5 vs. 9.5 +/- 0.6, p less than .05). We conclude that DBL is a major health problem for the ICU patient. Routine use of small specimen volumes in this setting is warranted. Recording DBL for use in physician decision-making also significantly impacts this problem and should be considered an important part of the ICU database. .A Foulke GE; Harlow DJ. .I 200838 .U 90004354 .S Crit Care Med 9001; 17(11):1156-8 .M Adult; Aged; Aged, 80 and over; Comparative Study; Critical Care/*; Head; Hemodynamics/*; Human; Intensive Care Units; Middle Age; Posture/*PH; Support, Non-U.S. Gov't. .T Modified head-up tilt test for orthostatic challenge of critically ill patients. .P JOURNAL ARTICLE. .W The purpose of this study was to assess the cardiovascular response to a modified head-up tilt test for use with the bedridden, critically ill patient. The cardiovascular responses of seven normals and ten critically ill patients to 45 degrees head-up tilt with the legs horizontal (0 degrees) were analyzed. Stroke volume index (SI) and cardiac index (CI) were measured with thoracic electric bioimpedance (TEB). The baseline TEB (Z0) was measured to monitor fluid shift out of the thorax during tilt. BP was measured and systemic vascular resistance index (SVRI) was calculated. Normals responded to the modified head-up tilt with a decreased SI (59 to 44 ml/m2 and CI (3.7 to 2.8 L/min.m2), and an increased SVRI and Z0 (25.5 to 27.9). As a group, the patients showed no significant change with tilt. However, individual analysis revealed a heterogeneous response by the patients. Those patients who demonstrated a caudal shift of blood (increased Z0) had decreased SI. Those with no indication of a caudal shift of blood, presumably due to decreased venous compliance, did not change SI. Thus, this type of modified head-up tilt can be used in the ICU to study more intensely cardiovascular function and control in the bedridden subject. .A Gotshall RW; Wood VC; Miles DS. .I 200839 .U 90004355 .S Crit Care Med 9001; 17(11):1159-65 .M Adult; Aged; Body Temperature/*; Circadian Rhythm/*; Female; Human; Intensive Care Units/*; Male; Middle Age; Prognosis; Rectum; Respiratory Insufficiency/MO/PP; Retrospective Studies. .T Retrospective study of temperature rhythms of intensive care patients. .P JOURNAL ARTICLE. .W The hourly rectal temperature record of 15 patients who spent greater than or equal to 8 days in the ICU were analyzed for circadian rhythmicity. Using cosinor analysis, a statistically significant rhythm in a period of 24 h was present on 80% of the patient days studied. The position of the acrophase, or peak, of the rhythm varied markedly both between patients and within patients, with changes of several hours from day to day. There was a tendency for the amplitude of the rhythm to be greater when the patients were unconscious than when they were conscious and in those patients who died compared with those who survived. .A Tweedie IE; Bell CF; Clegg A; Campbell IT; Minors DS; Waterhouse JM. .I 200840 .U 90004356 .S Crit Care Med 9001; 17(11):1166-9 .M Critical Care/*; Dobutamine/*AD; Dopamine/*AD; Female; Gestational Age; Hemodynamics/DE; Human; Hypotension/*DT; Infant, Newborn; Infant, Premature/*; Infusion Pumps; Male; Microcomputers; Prospective Studies. .T Response to dopamine and dobutamine in the preterm infant less than 30 weeks gestation. .P JOURNAL ARTICLE. .W Mean arterial pressure (MAP) and heart rate (HR) were studied in 12 hypotensive preterm neonates given dopamine. A significant, although temporary, elevation in MAP (8 +/- 3 mm Hg; p less than .01) occurred in five neonates in response to 5 micrograms/kg.min, but an increase in MAP was found in all infants (11 +/- 6 mm Hg; p less than .01) when the infusion rate was doubled. This elevation was sustained only in five who previously showed some response to the slower infusion. HR was unaffected except for an increase of 22 +/- 12 beat/min (p less than .01) in the five showing sustained MAP elevation with 10 micrograms/kg.min. Dobutamine failed to raise MAP in the seven who relapsed, and refractory shock resulted. We conclude that time should not be wasted when starting dopamine at less than 10 micrograms/kg.min in hypotensive preterm infants, as lower rates are unlikely to produce a response and delay may cause further compromise. .A Miall-Allen VM; Whitelaw AG. .I 200841 .U 90004357 .S Crit Care Med 9001; 17(11):1170-4 .M Animal; Bicarbonates/BL/*PD; Drug Interactions; Hemodynamics/DE; Hydrogen-Ion Concentration; Hydroxyethyl Starch/*TU; Lactates/BL; Liver/DE; Oxygen Consumption/*DE; Random Allocation; Resuscitation/*MT; Shock, Hemorrhagic/BL/*DT; Sodium/BL/*PD; Starch/*AA; Support, Non-U.S. Gov't; Swine. .T Effects of bicarbonate therapy on tissue oxygenation during resuscitation of hemorrhagic shock. .P JOURNAL ARTICLE. .W We investigated the effects of clinically appropriate doses of NaHCO3 on tissue oxygenation when hemorrhagic shock was corrected with hydroxyethyl starch (hetastarch) in 12 piglets. Six animals received colloid only while six received colloid and bicarbonate. Both groups recovered rapidly hemodynamically, but conjunctival, subcutaneous, and liver tissue PO2 values returned to baseline more slowly after bicarbonate administration. In the NaHCO3 group, pulmonary artery wedge pressure and arterial bicarbonate concentration were higher during early resuscitation, and arterial plasma lactate remained higher than in the control group at the end of the follow-up period. The delayed increase in tissue PO2 values after bicarbonate infusion may be explained, at least partly, by decreased arterial blood oxygenation and a shift of the oxyhemoglobin curve to the left. NaHCO3 adjunct has no added beneficial effect on hemodynamics and may be harmful to tissue oxygenation in hemorrhagic shock resuscitated with hetastarch. .A Makisalo HJ; Soini HO; Nordin AJ; Hockerstedt KA. .I 200842 .U 90004358 .S Crit Care Med 9001; 17(11):1175-80 .M Animal; Blood Pressure; Cardiac Output; Coronary Circulation/*; Electric Countershock; Heart-Assist Devices/*; Oxygen Consumption; Resuscitation/MT; Support, Non-U.S. Gov't; Swine; Ventricular Fibrillation/*TH. .T Effect of direct mechanical ventricular assistance on myocardial hemodynamics during ventricular fibrillation. .P JOURNAL ARTICLE. .W Direct mechanical ventricular assistance (DMVA) is a method of biventricular circulatory support that employs a pneumatic device to apply both systolic and diastolic forces directly to the ventricular myocardium. This study investigated the effects of DMVA on myocardial hemodynamics when applied after a prolonged cardiopulmonary arrest. Seven swine weighting 28.3 +/- 2.5 kg were instrumented for regional myocardial blood flow (MBF) measurements using tracer microspheres. Ventricular fibrillation was then induced. After 10 min of ventricular fibrillation, CPR was initiated for 3 min. DMVA was then applied through median sternotomy. Defibrillation was attempted after 3.5 min of DMVA. If unsuccessful, DMVA was instituted for another 17.5 min and a subsequent defibrillation attempt was made. Arterial oxygen content (CaO2), coronary sinus oxygen content (CcSO2), myocardial oxygen delivery/consumption (mDO2/mVO2), extraction ratio (ER), and endocardial/epicardial blood flow ratio (EN/EP) were determined during CPR, during the initial application of DMVA (DMVA1), and after the subsequent 17.5 min of DMVA in those animals not initially defibrillated (DMVA2). Three of the seven animals were successfully defibrillated during DMVA1. After the additional 17.5 min of DMVA, only one other animal was defibrillated. There was a significant improvement in CaO2, CcSO2, MBF, mDO2, mVO2, ER, and EN/EP after DMVA1 compared to CPR. Only mVO2 and ER improved significantly after DMVA2. These findings support the concept that physical diastolic augmentation may improve myocardial hemodynamics when DMVA is applied during cardiac arrest. .A Brown CG; Schlaifer J; Jenkins J; Anstadt GL; Werman HA; Tallman RD Jr; Ashton J; Hamlin RL; Anstadt MP. .I 200843 .U 90004359 .S Crit Care Med 9001; 17(11):1181-6 .M Animal; Blood Glucose; Blood Pressure; Calcium/*BL; Dogs; Electric Countershock/*MT; Heart Massage/*MT; Magnesium/*BL; Potassium/*BL; Resuscitation/MT; Support, Non-U.S. Gov't; Ventricular Fibrillation/BL/*TH. .T Postresuscitation electrolyte changes: role of arrhythmia and resuscitation efforts in their genesis. .P JOURNAL ARTICLE. .W Hypokalemia frequently occurs after resuscitation from ventricular fibrillation (VF) in man. To test the casual roles of VF and resuscitation variables in this electrolyte change, we studied six groups of dogs: VF with CPR and electrical cardioversion (n = 9), control dogs with no intervention (n = 9), CPR without arrhythmia (n = 5), electrical cardioversion without arrhythmia (n = 5), CPR and cardioversion without arrhythmia (n = 5), and rapid right ventricular pacing (n = 5) (pacing rate 374 +/- 68 beat/min; BP 79/52 mm Hg during pacing). Blood for K, Ca, Mg, and glucose analysis was collected before each intervention (or at baseline in control animals) and sequentially for 3 hr. Mg had a maximum change of 0.3 mEq/L in the VF group 7 min after resuscitation, but did not change in the other groups (p less than .005). Glucose had a maximum change of 79 mg/dl in the VF group 7 min after resuscitation but did not change in the other groups (p less than .005). Ca had a maximum decrease of 0.4 mg/dl in the VF group 15 min after resuscitation but did not decrease in the other groups (p less than .005). K had a maximum decrease of 0.8 mEq/L in the VF group 60 min after resuscitation, whereas decreases were less in the other groups (p less than .005). Thus, VF caused a rapid rise in Mg and glucose followed by a fall in Ca and K. These changes were independent of resuscitation efforts as well as the moderate hypotension induced by rapid right ventricular pacing.(ABSTRACT TRUNCATED AT 250 WORDS) .A Salerno DM; Murakami MM; Winston MD; Elsperger KJ. .I 200844 .U 90004360 .S Crit Care Med 9001; 17(11):1187-90 .M Animal; Blood Pressure/DE; Deferoxamine/*AD; Dogs; Hemofiltration/*; Iron/*PO/UR; Support, Non-U.S. Gov't. .T Continuous arteriovenous hemofiltration in experimental iron intoxication. .P JOURNAL ARTICLE. .W This study evaluated continuous arteriovenous hemofiltration (CAVH) as a method for removing the iron-deferoxamine complex in experimental iron intoxication. Five anesthetized dogs were instrumented for hemodynamic monitoring and then given 600 mg/kg of elemental iron as ferrous sulfate. After a 3-h absorption period, CAVH was begun from the femoral artery to femoral vein. Deferoxamine was infused into the arterial lines of the CAVH cartridge at increasing doses. We found a dose-dependent increase in the ultrafiltrate excretion of iron. However, most of the deferoxamine was excreted unbound. The efficiency of complex formation was greater at lower BP and ultrafiltrate formation rate, suggesting that inadequate mixing of deferoxamine with blood may occur when arterial administration is used. Iron excretion in the urine over the same time period was not significantly greater than that removed by CAVH. We conclude that CAVH can remove iron using deferoxamine as a chelating agent. .A Banner W Jr; Vernon DD; Ward RM; Sweeley JC; Dean JM. .I 200845 .U 90004361 .S Crit Care Med 9001; 17(11):1191-3 .M Blood Gas Analysis/*MT; Human; Regression Analysis; Respiration, Artificial; Respiratory Insufficiency/*BL/TH. .T Prediction of arterial oxygen partial pressure from intrapulmonary venous admixture. .P JOURNAL ARTICLE. .W A short program was developed to predict the PaO2 at a given FIO2 by using arterial and mixed venous blood gas data obtained at an FIO2 of 1.0. Our program resolves Adair's equation and the shunt equation inversely, on the assumption that intrapulmonary venous admixture and the arteriovenous oxygen content difference remain constant during the study. The study was conducted on 19 patients with respiratory failure who were intubated and mechanically ventilated. According to linear regression analysis, regression coefficients of 0.91 and 0.97 were obtained between the measured PaO2 values and those estimated by the arterial/alveolar oxygen tension ratio (PaO2/PaO2) and our program, respectively (n = 23). The PaO2 values were predicted more accurately by our program than those calculated by PaO2/PaO2. Because our program is simple enough to be carried out with a pocket computer, it may be helpful in a bedside decision of lowering FIO2, especially in patients who require a high FIO2 level to maintain sufficient arterial oxygenation. .A Ogawa S; Kusunoki M; Shirai J; Takeda K; Takezawa J; Taenaka N; Matsumoto M; Kamada T. .I 200846 .U 90004362 .S Crit Care Med 9001; 17(11):1194-8 .M Cardiac Output/*; Cardiography, Impedance/*; Human; Male; Observer Variation/*; Plethysmography, Impedance/*; Reproducibility of Results; Ultrasonics/*. .T Thoracic bioimpedance and Doppler cardiac output measurement: learning curve and interobserver reproducibility. .P JOURNAL ARTICLE. .W Nine previously untrained health professionals learned to measure cardiac output (Qt) by suprasternal continuous-wave Doppler ultrasound (QtDopp) and by thoracic bioimpedance (Qtbi). Each received standardized written, videotaped, and individual instruction. First the novice, then the reference examiner, measured QtDopp or Qtbi in triplicate in an adult male subject. The reference examiner was blind to the novice measurements and the novice was not informed of the reference measurements. Each novice repeatedly measured QtDopp or Qtbi in different subjects until the mean novice QtDopp or Qtbi was within 10% of the corresponding mean reference measurement in three of four consecutive subjects. The novice observers required an average of 12.9 +/- 3.5 trials to learn to measure QtDopp, and an average of 8.4 +/- 4.5 trials to learn to measure Qtbi. The likelihood of novice agreement with the reference improved with experience. The same degree of intraobserver variability as reported for Qt measured by thermodilution (coefficient of variance less than or equal to 10%) was achieved with Qtbi in 150 (99%) of 152 triplicate measurements and QtDopp in 216 (97%) of 222 triplicate measurements. More importantly, interobserver agreement (within 10%) was achieved with both Qtbi and QtDopp. Reproducible noninvasive Qt measurement will allow these techniques to be used to monitor trend changes in Qt. .A Wong DH; Onishi R; Tremper KK; Reeves C; Zaccari J; Wong AB; Miller JB; Cordero V; Davidson J. .I 200847 .U 90004365 .S Crit Care Med 9001; 17(11):1223-7 .M Adult; Age Factors; Aged; Aged, 80 and over; Comparative Study; Coronary Care Units; Female; Human; Intensive Care Units/*; Male; Middle Age; Patient Acceptance of Health Care/*; Questionnaires; Severity of Illness Index. .T Comparison of the reactions of older and younger patients to intensive care. .P JOURNAL ARTICLE. .W To determine whether age affected the attitudes of patients to intensive care, we administered a questionnaire to 57 patients who had been hospitalized in our ICU or coronary care unit (CCU). The 28 men and 29 women ranged in age from 20 to 92 yr (mean 58.4). Nineteen patients were greater than or equal to 70 yr and nine were greater than or equal to 80 yr. The "intensity" and "severity" of the treatments were similar in the older and younger patients, both men and women, in the ICU and CCU. The great majority of the patients, both old and young, were satisfied with their treatment and outcome, and expressed willingness to undergo similar treatment(s) in the future, if needed. Only five patients were dissatisfied with their treatment: two were greater than 70 yr, the other three were 27, 62, and 65 yr. We did not interview a large number of patients and thus, cannot draw far-reaching conclusions without additional study. Nevertheless, although we expected that older patients would be particularly distressed about their treatments and hence, say they would decline them in the future, in this study both the older and the younger patients were highly accepting of the treatment they received. .A Fulop M; Adel HN; Webster A; Levin G. .I 200848 .U 90004366 .S Crit Care Med 9001; 17(11):1228-30 .M Adult; Aortic Diseases/*CO; Bronchial Fistula/*CO; Case Report; Cause of Death; Chronic Disease; Fistula/*CO; Hemoptysis/*ET/PP/RA; Human; Male; Prosthesis Failure. .T Fatal hemoptysis: aortobronchial fistula as a preventable cause of death. .P JOURNAL ARTICLE. .W Hemoptysis as a result of leaking aortic aneurysms occurs rarely and has a high fatality rate. A case of chronic hemoptysis resulting from an aortobronchial fistula in a patient with an aortic prosthesis is reported. Hemoptysis, even when chronic, should prompt investigation of the possibility of a leaking graft in patients with prosthetic aortic grafts. Chest x-ray and bronchoscopy usually yield nonspecific findings. Aortography may demonstrate an aortic aneurysm and is the preferred diagnostic procedure; however, an aggressive surgical approach is often necessary. .A Wheeler AP; Loyd JE. .I 200849 .U 90004367 .S Crit Care Med 9001; 17(11):1231-2 .M Adolescence; Case Report; Electrocardiography; Equipment Failure; Female; Human; Pacemaker, Artificial/*; Postoperative Period; Tachycardia/*ET. .T Runaway temporary pacemaker caused by a component defect. .P JOURNAL ARTICLE. .A Tilden SJ; Koopot R; Sansbury D; Williams R. .I 200850 .U 90004368 .S Crit Care Med 9001; 17(11):1233 .M Alcohol, Propyl/*PO; Case Report; Female; Human; Middle Age; Skin Absorption/*. .T Absorption of topical isopropyl alcohol in an adult [letter] .P LETTER. .A McGrath RB; Einterz R. .I 200851 .U 90004369 .S Crit Care Med 9001; 17(11):1233-4 .M Case Report; Ergotism/*DT; Female; Ferricyanides/*TU; Heart Arrest/*CI; Human; Middle Age; Nitroprusside/*TU. .T Ergot poisoning and cardiac arrest [letter] .P LETTER. .A Lopez Rodriguez A; Gomez Coronado VJ; Julia Navaraez JA; Rebollo J; Garcia Lombardo A. .I 200852 .U 90004371 .S Crit Care Med 9001; 17(11):1235 .M Adult; Amikacin/*PK; Bacterial Infections/*ME; Case Report; Critical Care; Female; Human. .T Where has all the amikacin gone? [letter] .P LETTER. .A Ludik P; Lichtman AR. .I 200853 .U 90004372 .S Crit Care Med 9001; 17(11):1236 .M Anesthesia, General; Animal; Embolism, Air/*CI; Nitrous Oxide/*AE. .T Effect of nitrous oxide on air bubble volume in arterial air embolism [letter] .P LETTER. .A Garcia C; Albin MS; Bunegin L. .I 200854 .U 90004373 .S Crit Care Med 9001; 17(11):1236-7 .M Cross Infection/*PC; Equipment Contamination/PC; Human; Pneumonia/*ET; Respiration, Artificial/*AE. .T Selective decontamination in ventilated patients [letter] .P LETTER. .A Inglis TJ; Hawkey PM. .I 200855 .U 90004502 .S Chest 9001; 96(4):707-8 .M Adult; Human; Lung Transplantation/*/PH; Male; Middle Age; Pulmonary Emphysema/*SU. .T The other lung--revisited [editorial] .P EDITORIAL. .A Cooper JD. .I 200856 .U 90004503 .S Chest 9001; 96(4):708-10 .M Bronchoscopy/*UT; England; Fiber Optics/IS; Human; Lung Diseases/*DI; Physician's Practice Patterns/*; United States. .T Enticements for fruitless bronchoscopy [see comments] .P JOURNAL ARTICLE. .A Rohwedder JJ. .I 200857 .U 90004504 .S Chest 9001; 96(4):710-2 .M Bronchoalveolar Lavage Fluid/AN; Bronchoscopy/*UT; Costs and Cost Analysis; Fiber Optics/IS; Human; Lung Diseases/*DI; Lung Neoplasms/DI; Physician's Practice Patterns/*; United States. .T Bronchoscopy. Enough or too much? .P JOURNAL ARTICLE. .A Sen RP; Walsh TE. .I 200858 .U 90004506 .S Chest 9001; 96(4):713-4 .M Acquired Immunodeficiency Syndrome/*CO; Aerosols; Human; Opportunistic Infections/CO; Pentamidine/*AD/TU; Pneumonia, Pneumocystis carinii/CO/*DT. .T Aerosolized pentamidine for Pneumocystis carinii pneumonia [editorial] .P EDITORIAL. .A Luce JM; Hopewell PC. .I 200859 .U 90004507 .S Chest 9001; 96(4):714-5 .M Acquired Immunodeficiency Syndrome/*CO; Critical Care/*; Human; Opportunistic Infections/*CO; Pneumonia, Pneumocystis carinii/*CO; Prognosis; Respiratory Insufficiency/ET/*TH. .T Intensive care for patients with Pneumocystis carinii pneumonia and respiratory failure. Are we prepared for our new success? [editorial] .P EDITORIAL. .A Wachter RM; Luce JM. .I 200860 .U 90004508 .S Chest 9001; 96(4):716 .M Anoxemia/*CO/PP; Cardiac Output; Human; Oxyhemoglobins/ME; Sleep Apnea Syndromes/BL/*ET. .T Nocturnal hypoxemia in sleep apnea [editorial] .P EDITORIAL. .A Findley LJ. .I 200861 .U 90004509 .S Chest 9001; 96(4):717-22 .M Human; Hydrogen-Ion Concentration; Male; Middle Age; Monitoring, Physiologic; Obesity/PP; Oximetry; Oxyhemoglobins/*ME; Pulmonary Gas Exchange; Sleep Apnea Syndromes/*BL/PP. .T The rate of fall of arterial oxyhemoglobin saturation in obstructive sleep apnea. .P JOURNAL ARTICLE. .W During breath holding, correlations have been demonstrated between the rate of fall of arterial oxyhemoglobin saturation (dSaO2/dt) and the following: thoracic gas volume at apnea onset, resting oxygen consumption, preapneic arterial oxyhemoglobin saturation (SaO2) and obesity. A key factor influencing dSaO2/dt is mixed venous oxyhemoglobin saturation (SvO2) as recently demonstrated in an animal model of obstructive apnea. The purpose of the present study was to see if dSaO2/dt was related to SvO2 during sleep in a group of subjects with severe obstructive sleep apnea (OSA) and varying levels of SvO2. Eight OSA subjects were studied during sleep with indwelling arterial and central venous catheters. Continuous SaO2 was measured by ear oximetry while continuous SvO2 was measured through the fiberoptic bundle of a Shaw Opticath catheter. Thirty percent or more of all obstructive apneas were scored for duration, preapneic SaO2, SvO2 and dSaO2/dt. Least squares regression was used to examine the relationship between dSaO2/dt and other measured variables. The dSaO2/dt showed a consistent negative correlation with preapneic SvO2 and was not related to duration. Mean dSaO2/dt during sleep correlated to some degree with the degree of gas exchange (Qva/Qt) abnormality prior to sleep. It is concluded that in humans, SvO2 plays a substantial role in determining dSaO2/dt. Potentially, the presence of gas exchange abnormalities (eg, found in intrinsic lung disease) causing hypoxemia and low SvO2 may steepen dSaO2/dt, lowering the nadir level of apneic desaturation for the same duration of apnea found in a patient with more normal gas exchange. .A Fletcher EC; Costarangos C; Miller T. .I 200862 .U 90004510 .S Chest 9001; 96(4):723-8 .M Acquired Immunodeficiency Syndrome/*CO; Adult; Comparative Study; Human; Lung Neoplasms/ET/*RA; Male; Middle Age; Mycobacterium avium-intracellulare Infection/RA; Pneumonia, Pneumocystis carinii/RA; Retrospective Studies; Sarcoma, Kaposi's/ET/*RA; Tomography, X-Ray Computed. .T Kaposi's sarcoma. CT-radiographic correlation. .P JOURNAL ARTICLE. .W The role of CT in the diagnosis of intrathoracic Kaposi's sarcoma (KS) was evaluated retrospectively in 24 patients, in the absence of coexistent opportunistic infections. In all cases the diagnosis of KS was initially established by histologic evaluation of extrathoracic disease: 15 patients had verified parenchymal KS and nine patients endobronchial KS. (Chest roentgenograms were analyzed separately for each group: in 14 patients serial films were available for review. The predominant radiographic findings was the presence of nonspecific, bilateral, perihilar infiltrates in 22 of 24 cases (92 percent). Corresponding CT scans documented the presence of abnormal hilar densities characteristically extending into the adjacent pulmonary parenchyma along distinctly perivascular and peribronchial pathways. Discrete, poorly marginated nodules were identified radiographically in ten cases (42 percent); these proved to be randomly distributed throughout the parenchyma on CT. Radiographic evidence of mediastinal adenopathy was distinctly unusual, seen in only two cases (8 percent). While CT typically demonstrated shotty adenopathy, significantly enlarged nodes (greater than 1 cm) were rarely identified. We concluded that CT is more specific than routine roentgenograms for identifying pulmonary KS. While not pathognomonic, peribronchial and perivascular disease is sufficiently characteristic to obviate more invasive diagnostic procedures, especially in patients with established KS. .A Naidich DP; Tarras M; Garay SM; Birnbaum B; Rybak BJ; Schinella R. .I 200863 .U 90004511 .S Chest 9001; 96(4):729-37 .M Anoxemia/*CO; Female; Heart Catheterization; Human; Hypercapnia/*CO; Hypertension, Pulmonary/*CO; Male; Middle Age; Monitoring, Physiologic; Prospective Studies; Respiratory Function Tests; Sleep Apnea Syndromes/*CO/DI. .T Pulmonary hypertension, hypoxemia, and hypercapnia in obstructive sleep apnea patients. .P JOURNAL ARTICLE. .W To define the parameters of respiratory insufficiency in OSA, 114 consecutive patients (108 men, six women) were prospectively studied. In addition to standard polysomnography, they underwent pulmonary function tests, right heart catheterization, and ventilatory response tests to hypercapnia. Nineteen patients (19 percent) had a resting PAP greater than or equal to 20 mm Hg. Multiple regression analysis showed that FEV1 and PaO2 (both with a negative coefficient) and PaCO2 (with a positive coefficient) significantly contributed to PAP. Thirteen patients (12 percent) had a PaCO2 greater than or equal to 45 mm Hg. A multiple regression analysis showed that FEV1 and the minute ventilation at PETCO2 = 60 mm Hg (both with a negative coefficient) and the cumulative apnea duration (with a positive coefficient) significantly contributed to PaCO2. Thirty-seven patients (33 percent) had a PaO2 less than or equal to 65 mm Hg. A multiple regression analysis showed that FEV1 (with a positive coefficient) and the hypopnea + apnea index (with a negative coefficient) significantly contributed to PaO2. These data confirm that impaired daytime pulmonary function (diffuse airway obstruction) contributes to the development of daytime pulmonary hypertension, hypoxemia, and hypercapnia in OSA patients. They show that the amount of sleep-related breathing disorders also plays a significant role. .A Krieger J; Sforza E; Apprill M; Lampert E; Weitzenblum E; Ratomaharo J. .I 200864 .U 90004512 .S Chest 9001; 96(4):738-42 .M Case Report; Exercise; Exercise Test; Human; Immunosuppressive Agents/TU; Lung Diseases, Obstructive/*SU; Lung Transplantation/*/PH; Male; Middle Age; Pulmonary Gas Exchange; Ventilation-Perfusion Ratio. .T Single lung transplantation for severe chronic obstructive pulmonary disease. Washington University Lung Transplant Group. .P JOURNAL ARTICLE. .W Single lung transplantation (SLT) has been considered physiologically inappropriate for patients with chronic obstructive pulmonary disease (COPD). It has been postulated that the high static compliance and elevated pulmonary vascular resistance of the native lung functioning in parallel with the more normal allografted lung could cause unacceptable ventilation-perfusion mismatching and/or overinflation of the native lung with encroachment on the expansion of the transplanted lung. While some degree of ventilation-perfusion imbalance may be physiologically obligatory after SLT for COPD, a significant disruption in gas exchange may not occur unless a complication, such as rejection or infection, arises in the transplanted lung. A 60-year-old man with COPD who underwent successful SLT is presented and discussed. In spite of scintigraphic evidence of ventilation-perfusion mismatching between the native lung and the allograft during the first six postoperative weeks, the recipient had normal resting gas exchange on room air after the second postoperative week. Fourteen weeks after transplantation, his maximum oxygen uptake was 37.3 percent of the predicted maximal value, and no evidence of ventilatory limitation was detected. His functional status and lifestyle have been markedly improved by SLT. The role of SLT for COPD should be reconsidered. It may be a reasonable transplantation alternative for selected patients with COPD who are not candidates for double lung transplantation (DLT). .A Trulock EP; Egan TM; Kouchoukos NT; Kaiser LR; Pasque MK; Ettinger N; Cooper JD. .I 200865 .U 90004513 .S Chest 9001; 96(4):743-6 .M Adult; Body Height; Female; Human; Lung/*PH; Lung Volume Measurements; Male; Pulmonary Diffusing Capacity; Respiration/*GE; Spirometry; Twins/*GE. .T Heritability estimates of pulmonary function. .P JOURNAL ARTICLE. .W To test the hypothesis that there is genetic control of pulmonary function parameters independent of that influencing height, we evaluated 74 pairs of asymptomatic, nonsmoking twins. FVC, FEV1, FEF25-75%, TLCsb, RVsb, Dsb, and D/VA were measured. Pulmonary function indices were adjusted for height using simple linear regression. Mean intrapair differences (unadjusted and adjusted for height) were compared using t tests of independent samples. Within pair, Holzinger's, and Falconer's heritability estimates were calculated using height-adjusted residual values. When total variances of a function parameter were statistically different between monozygotes and dizygotes, the among component heritability estimate was calculated and used as the best indicator of heritability. Following adjustment for height, no measure of pulmonary function which satisfied the requirements of the analysis was found to be significantly heritable. .A Ghio AJ; Crapo RO; Elliott CG; Adams TD; Hunt SC; Jensen RL; Fisher AG; Afman GH. .I 200866 .U 90004514 .S Chest 9001; 96(4):747-51 .M Aged; Aged, 80 and over; Aging/*PH; Electroencephalography; Human; Male; Middle Age; Monitoring, Physiologic; Reproducibility of Results; Respiration/*PH; Sleep/*PH; Sleep Apnea Syndromes/DI; Support, U.S. Gov't, Non-P.H.S.. .T Consistency of respiratory measurements from night to night during the sleep of elderly men. .P JOURNAL ARTICLE. .W Fourteen healthy elderly men had polysomnography performed on two consecutive nights to assess the consistency of sleep and breathing from night to night. The reported first-night effect was seen on electroencephalographic sleep, leading to lighter or fitful sleep on the first night. Mean values for apneas, hypopneas, and oxygen desaturations did not change from night 1 to night 2. Five of 14 subjects would have changed classification from night to night if a cutoff of five apneas and hypopneas per hour were used to define normality. Because this numerical cutoff may not be valid in the elderly, the clinical significance of such a changing classification is not clear. .A Aber WR; Block AJ; Hellard DW; Webb WB. .I 200867 .U 90004515 .S Chest 9001; 96(4):752-6 .M Adult; Asthma/*DI/PP; Bronchial Provocation Tests; Female; Forced Expiratory Volume; Histamine/DU; Human; Male; Pulmonary Gas Exchange/*; Respiratory Dead Space; Ventilation-Perfusion Ratio. .T Pulmonary gas exchange during histamine-induced bronchoconstriction in asthmatic subjects. .P JOURNAL ARTICLE. .W Bronchial provocation for testing airway hyperreactivity is now well-established. However, the effects of histamine-induced bronchoconstriction on pulmonary gas exchange in man have not been systematically studied. We empirically noted marked decreases in PaO2 in some asthmatic subjects following induced bronchoconstriction. Nine subjects with mild, stable asthma were studied, each on two separate days. The first determined the dose of inhaled histamine necessary to decrease FEV1 by 20 percent and the relationship to lung volume and to pulmonary resistance by the interrupter technique (Rint). On the second day arterial blood gases, ventilation, Rint, and the anatomic (VDan) and physiologic (VDphys) dead spaces were measured simultaneously. There was a significant (p less than 0.05), profound fall in PaO2 (mean, -21.8 mm Hg) and in P(A-a)O2 (mean +14.7 mm Hg) within 5 min after bronchoconstriction, associated with a significant (p less than 0.05) increase in respiratory frequency (mean +5.1 min-1); and decrease in tidal volume (mean, -0.3 L). The ratio VDphys/VT increased significantly (p less than 0.05; mean change, +0.08) even though VDan and VDphys did not. Bronchoconstriction induced the broadening of ventilation (V)/perfusion (Q) ratios, with, most likely, an increase in areas of high V/Q. Histamine-induced bronchoconstriction in mild asthma results in a marked fall in PaO2 due to induced V/Q inequality. Therefore, histamine airway challenge should be used with caution in patients with any preexisting hypoxemia. .A Burke TV; Kung M; Burki NK. .I 200868 .U 90004518 .S Chest 9001; 96(4):767-71 .M Comparative Study; Dyspnea/*DI; Exercise Test; Female; Human; Male; Middle Age; Pulmonary Fibrosis/*DI/PP; Respiratory Function Tests; Sensation/PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Measurement of respiratory sensation in interstitial lung disease. Evaluation of clinical dyspnea ratings and magnitude scaling. .P JOURNAL ARTICLE. .W To evaluate measurements of respiratory sensation in ILD, we compared ratings of breathlessness from three clinical scales with the perceived magnitude of added elastic loads in 20 symptomatic ILD patients. Dyspnea ratings were obtained by two independent observers for each clinical method. Perceived magnitude of four elastic loads was selected from the Borg category scale; these estimates were summarized using the psychophysical power function equation. Ten age-matched healthy subjects also scaled the magnitude of added elastic loads. Dyspnea ratings from the three clinical scales were significantly interrelated. Mean exponents for mouth pressure developed during elastic loading were similar in the patient and control groups. Dyspnea ratings and exponents for elastic loads were not significantly correlated in ILD patients. Of the physiologic parameters examined, Dsb and gas exchange during exercise correlated significantly with clinical dyspnea ratings; none correlated with the exponent for added elastic loads. These data demonstrate that clinical dyspnea ratings provide valid measures of breathlessness in patients with ILD which are independent of the perception of respiratory loads. .A Mahler DA; Harver A; Rosiello R; Daubenspeck JA. .I 200869 .U 90004519 .S Chest 9001; 96(4):772-8 .M Bronchodilator Agents/*TU; Depression, Chemical; Female; Human; Male; Middle Age; Respiration, Artificial/*; Respiratory Airflow/DE; Respiratory Insufficiency/PP/*TH; Respiratory Mechanics/*DE; Support, Non-U.S. Gov't; Theophylline/*AA/TU; Time Factors. .T Doxofylline and respiratory mechanics. Short-term effects in mechanically ventilated patients with airflow obstruction and respiratory failure. .P JOURNAL ARTICLE. .W To assess the short-term effects of a methylxanthine (doxofylline) on respiratory mechanics in mechanically ventilated patients with airway obstruction and respiratory failure, nine consecutive patients were examined within three days from the onset of mechanical ventilation. Flow, changes in pulmonary volume, and Paw were measured using a ventilator (Servo 900C). End-expiratory and end-inspiratory airway occlusion was performed to measure PEEPi, Cstrs, Rrsmax, and Rrsmin. Measurements were performed before and at 5, 15, and 30 minutes after an intravenous loading dose of doxofylline (5 to 6 mg/kg). We found that doxofylline determined, on the average, a marked decrease in respiratory resistance (Rrsmax and Rrsmin, -27.2 percent and -36.5 percent, respectively) without significant changes in Cstrs and Pmax. The PEEPi, reflecting pulmonary dynamic hyperinflation, was also significantly decreased by doxofylline (-41 percent, on the average). The Pmax was not reliable for evaluation of a single patient, since changes in the elastic pressure can offset changes in the resistive one. No patient experienced significant side effects due to doxofylline. We conclude that (1) the effects of therapy can be assessed noninvasively at bedside in critically ill patients; (2) doxofylline is a rapid and efficient bronchodilator in mechanically ventilated patients with ARF and airflow obstruction; and (3) the decrease in the respiratory resistance and PEEPi, associated with an improved mechanical efficiency of the respiratory muscles at a lower pulmonary volume, can provide better conditions for the patient-ventilator interaction and for weaning. .A Poggi R; Brandolese R; Bernasconi M; Manzin E; Rossi A. .I 200870 .U 90004520 .S Chest 9001; 96(4):779-83 .M Adult; Aged; Coin Lesion, Pulmonary/*RA; Human; Lung Neoplasms/RA; Middle Age; Models, Structural; Tomography, X-Ray Computed/*MT. .T Computerized tomographic densitometry of the solitary pulmonary nodule using a nodule phantom. .P JOURNAL ARTICLE. .W The successful application of computerized tomographic density analysis for evaluating the solitary pulmonary nodule has previously been described and the technique has since been simplified by using a calcium-equivalent nodule reference phantom. Because published experience with this technique remains limited, the current research reports the Cleveland Clinic experience with the CIRS model III pulmonary nodule reference phantom. Without knowledge of the final diagnosis, the nodule phantom was used as the standard for categorizing 31 nodules in 29 patients as either benign or indeterminate. Secure diagnoses were obtained in all cases. Eleven nodules were called benign and ten proved so, whereas 20 nodules were classified as indeterminate. One lesion, an adenocarcinoma, was falsely called benign using this technique. The excellent density discrimination achieved with CT makes this a superior tool for analysis of the solitary pulmonary nodule, and the nodule reference phantom has greatly simplified the technique of CT densitometry. As demonstrated by this and prior studies, calcification is not a unique feature of the benign lesion and successful clinical application of this technique requires cautious interpretation of results. .A Jones FA; Wiedemann HP; O'Donovan PB; Stoller JK. .I 200871 .U 90004522 .S Chest 9001; 96(4):790-3 .M Adolescence; Adult; Asthma/*CO/DT/PX; Bronchodilator Agents/TU; Case Report; Death, Sudden/*ET; Female; Human; Male; Support, Non-U.S. Gov't; Time Factors. .T Unexpected, unexplained sudden death in young asthmatic subjects. .P JOURNAL ARTICLE. .W The clinical course of asthma in four patients younger than 25 years was considered. Three died unexpectedly of their disease, and the fourth was successfully resuscitated after cardiopulmonary arrest. None of these patients met the criteria for status asthmaticus in the period preceding their death. The time course of the illness from apparent wellness to death was documented as seconds to minutes. No obvious cause of the severe disease was found at postmortem in two patients or by clinical analysis in all four. Patients with bronchial asthma may die with this disease unexpectedly, rapidly and with no obvious cause for the severity of this process. .A Robin ED; Lewiston N. .I 200872 .U 90004523 .S Chest 9001; 96(4):794-8 .M Antibody-Dependent Cell Cytotoxicity/IM; B-Lymphocytes/*IM; Bronchoalveolar Lavage Fluid/CY; Human; Lung/*PA; Lymphocyte Transformation/*IM; Prednisone/*TU; Pulmonary Fibrosis/*DT/IM. .T Association of activated cytolytic lung lymphocytes with response to prednisone therapy in patients with idiopathic pulmonary fibrosis. .P JOURNAL ARTICLE. .W Previous studies have suggested that immunologic mechanisms may contribute to pathogeneic reactions in certain interstitial lung diseases. Cytolytic lymphocytes are major effector cells of the immune response that have not been extensively studied in these disorders. To investigate the role of activated cytolytic lymphocytes in IPF, we studied B-cell and monocyte/macrophage-depleted lymphocyte preparations isolated from BAL fluid and peripheral blood of patients with this disease (n = 10) and used a lectin-dependent cytotoxicity assay to detect activated cytolytic lymphocytes. In longitudinal studies, those patients who had cytolytic activity of BAL fluid lymphocytes (range, 8 to 35 percent, n = 4) showed significant improvement in pulmonary function (mean increase in diffusing capacity, 30 +/- 2 percent) in association with decreased BAL fluid cytolytic lymphocyte activity after prednisone treatment. In contrast, patients who initially lacked cytolytic activity in BAL fluid (n = 6) did not improve with prednisone. Activated cytolytic lymphocytes were not observed in the BAL fluid of healthy subjects. These investigations suggest a causal relationship between activated cytolytic lymphocytes in the lung and disease activity in IPF and that assays of activated cytolytic lymphocytes are helpful in identifying patients who will improve with immunosuppressive therapy. .A Karpel JP; Norin AJ. .I 200873 .U 90004524 .S Chest 9001; 96(4):799-804 .M Adult; Human; Lung/PH/*RA; Male; Posture; Pulmonary Circulation/PH; Respiration/PH; Tomography, X-Ray Computed/*MT; Xenon/DU. .T Local pulmonary ventilation using nonradioactive xenon-enhanced ultrafast computed tomography. .P JOURNAL ARTICLE. .W Using ultrafast computed tomography, we have developed a technique for measuring local ventilation in a volume of 1 cm3 in the normal supine lung. The technique employs the inert gas xenon in its nonradioactive form and makes use of its radiopaque properties. The inhalation of xenon results in changes in density which can be detected and measured in Hounsfield units using ultrafast computed tomography. Using this property and assuming a monoexponential form for the washin curve of the inert gas, it is possible to calculate ventilation at a local level. The methodology also permits measurements of minute ventilation during the procedure, thus permitting standardization. Using this technique, we calculated local ventilation in six normal subjects and have demonstrated a minor gradient in ventilation between the dorsal and ventral regions of the lung while in the supine position. .A Murphy DM; Nicewicz JT; Zabbatino SM; Moore RA. .I 200874 .U 90004525 .S Chest 9001; 96(4):805-8 .M Acquired Immunodeficiency Syndrome/*CO; Adult; Comparative Study; Echocardiography; Electrocardiography; Heart Diseases/*CO/DI; Homosexuality; Human; Male; Middle Age; Myocardial Contraction; Pericardial Effusion/CO. .T Unsuspected cardiac abnormalities in the acquired immune deficiency syndrome. An echocardiographic study [see comments] .P JOURNAL ARTICLE. .W To investigate the frequency of unsuspected cardiac abnormalities in AIDS, M-mode and two-dimensional echocardiograms were performed on 27 homosexual males with this syndrome. Twenty-one homosexual males without the disease were used as controls. Subjects with clinical heart disease or a history of intravenous drug abuse were excluded. Fractional shortening was reduced in eight patients (30 percent) and in one control (5 percent) (p less than 0.05). Pericardial effusions were found in seven patients (26 percent); one control subject had a small effusion (5 percent) (p = 0.05). Overall, echocardiographic abnormalities were found in 13 of 27 patients (48 percent) compared with 2 of 21 control subjects (10 percent) (p less than 0.02). We conclude that although often not diagnosed clinically, the incidence of cardiac involvement in AIDS is high. .A Hecht SR; Berger M; Van Tosh A; Croxson S. .I 200875 .U 90004527 .S Chest 9001; 96(4):815-8 .M Antitubercular Agents/TU; Chicago; Comparative Study; Documentation; Drug Therapy, Combination; Female; Follow-Up Studies; Human; Male; Medical Records; Nurse Clinicians; Outpatient Clinics, Hospital/*OG; Patient Compliance/*; Specialism; Tuberculosis, Pulmonary/*PC. .T The tuberculosis clinic. .P JOURNAL ARTICLE. .W Patient compliance is the major obstacle to successful treatment of tuberculosis. To counter factors of inconstant attention to compliance, inconsistent follow-up, and incomplete documentation, a tuberculosis clinic, managed by nurse specialists, was established. To evaluate this clinic, records of all patients with tuberculosis followed-up there were compared with patients with tuberculosis observed in the other clinics over a nine-year period. Twelve percent of patients in the general clinics group had complete, documented, effective treatment compared with 86 percent in the tuberculosis clinic group. Only 31 percent of the general clinics patients compared with 100 percent of the tuberculosis clinic patients had completely documented follow-up. In hospitals in endemic areas for tuberculosis, a tuberculosis clinic may be superior to general clinics for the care of patients with tuberculosis. Staff of a specialized clinic can quickly identify a break in therapy, provide support necessary for better compliance, lessen the number of incomplete records, and decrease the number of patients who do not receive full therapy. .A Werhane MJ; Snukst-Torbeck G; Schraufnagel DE. .I 200876 .U 90004528 .S Chest 9001; 96(4):819-23 .M Adult; Byssinosis/*EP; California/EP; Comparative Study; Cotton/*AE; Cough/EP; Forced Expiratory Flow Rates; Forced Expiratory Volume; Human; Longitudinal Studies; Male; Prospective Studies; Support, Non-U.S. Gov't; Textile Industry; Vital Capacity. .T A longitudinal study of pulmonary function in cotton gin workers in the San Joaquin Valley. .P JOURNAL ARTICLE. .W In a previous study we found no significant effects of acute exposure to the cotton gin environment on FEV1 in San Joaquin Valley gin workers compared with concurrent control subjects, nor was there an excess of obstructive lung disease among the same gin workers. The present study looked at the mean annual decline in FEV1, FEV1/FVC, and FEF25-75% in San Joaquin Valley cotton gin workers vs concurrent control subjects over four years. The FEV1 of gin workers completing all four years of the study declined 27.3 ml vs 35.5 ml in control subjects (p = 0.37); FEV1/FVC declined 0.21 percent in gin workers and 0.23 percent in control subjects (p = 0.86); FEF25-75% declined 0.058 L/s in gin workers and 0.066 L/s in control subjects (p = 0.68). Also, the mean annual rate of change of FEV1 was less among the gin workers who did not complete all four years than the gin workers completing all four years. The presence of "byssinosis" symptoms did not significantly influence the results. This prospective, longitudinal study failed to find any detrimental effect of the cotton gin environment on the rate of decline of FEV1, FEV1/FVC, and FEF25-75%. This result was independent of "byssinosis" symptoms and the effect of "dropouts." .A Larson RK; Barman ML. .I 200877 .U 90004529 .S Chest 9001; 96(4):824-30 .M Aged; Electromyography; Female; Human; Lung Volume Measurements; Male; Middle Age; Pulmonary Fibrosis/DI/*PP; Respiratory Function Tests; Respiratory Mechanics/*PH; Respiratory Muscles/*IR; Support, Non-U.S. Gov't. .T Neural respiratory drive and neuromuscular coupling during CO2 rebreathing in patients with chronic interstitial lung disease. .P JOURNAL ARTICLE. .W In 12 patients with CILD and 18 age-matched normal subjects we assessed the ventilatory control system at three levels: (a) neural, as assessed by EMGd (XP/Ti) and EMGint muscles via surface electrodes; (b) muscular, as assessed by mouth occlusion pressure (P0.1); and (c) ventilatory, as assessed by both ventilation (VE) and the related parameters, tidal volume (VT) and respiratory frequency (f). Compared with a normal control group, patients exhibited a significant decrease in lung volumes and in MIP; VT and inspiratory time (Ti) were significantly lower, while VT/Ti, P0.1, and both EMGd and EMGint were significantly greater in patients. During a CO2 rebreathing test, patients exhibited significantly greater EMGd, EMGint, and P0.1 responses to increasing PETCO2 than the control group. VE response slopes were similar in the two groups. For a given EMGd response slope (delta XP/Ti/delta PETCO2), the average P0.1 response slope (delta P0.1/delta PETCO2) was found to be significantly lower in patients than in the normal control group. Compared with normal subjects, CILD patients have a normal or increased neural component of respiratory activity and relatively low neuromuscular coupling (delta P0.1/delta XP/Ti). The decreased neuromuscular coupling could be explained in these patients by a reduced inspiratory muscle strength. .A Gorini M; Spinelli A; Ginanni R; Duranti R; Gigliotti F; Arcangeli P; Scano G. .I 200878 .U 90004530 .S Chest 9001; 96(4):831-4 .M Adult; Aged; Female; Human; Male; Penicillins/TU; Pneumonia/DT/*ET; Sputum/MI; Streptococcal Infections/DT/*MI; Streptococcus/IP. .T Primary Streptococcus viridans pneumonia. .P JOURNAL ARTICLE. .W We describe three cases of acute uncomplicated bacterial pneumonia due to viridans streptococci in previously healthy adults, which were indistinguishable from those caused by other well-known respiratory pathogens. On arrival, all of these patients were treated with IV aqueous penicillin based on Gram stain of sputum which showed predominant Gram-positive cocci in pairs and chains. These specimens of sputum grew normal oral flora in the three cases. The diagnosis was confirmed by positive blood cultures in all three patients from each of two separate samples of blood. The isolates were identified as S uberis. There is no precedent in the literature of primary pneumonia due to viridans streptococci complicated by bacteremia in normal adults. We wonder if primary pneumonia due to viridans streptococci is not as rare as has been reported in the literature. Also, Gram stain of the sputum had a very significant contribution in the initial management of these patients. All of these patients subjectively showed improvement in 24 hours and became afebrile within three days of starting penicillin therapy. .A Sarkar TK; Murarka RS; Gilardi GL. .I 200879 .U 90004531 .S Chest 9001; 96(4):835-9 .M Adult; Bronchoscopy; Diagnosis, Differential; Female; Hong Kong/EP; Human; HIV Seropositivity; Immune Tolerance/*; Incidence; Male; Opportunistic Infections/ET; Tuberculosis, Pulmonary/DI/*EP. .T High incidence of pulmonary tuberculosis in the non-HIV infected immunocompromised patients in Hong Kong. .P JOURNAL ARTICLE. .W In areas where tuberculosis is endemic, clinicians managing immunocompromised patients (ICP) are confronted with the possibility of Mycobacterium tuberculosis as a pathogen. To determine the incidence and clinical pattern of, the diagnostic approach to, and potential therapeutic implications of pulmonary tuberculosis in this patient population, we reviewed 62 non-HIV infected ICP in Hong Kong who had bronchoscopy because of pulmonary infiltrates. Pulmonary tuberculosis was the second most common cause after bacterial infections. Clinical and radiographic presentations of 12 patients with tuberculosis were nonspecific. Flexible bronchoscopy for tuberculosis carried a diagnostic sensitivity of 91.7 percent. We conclude that for the non-HIV infected ICP from areas where tuberculosis is endemic: M tuberculosis should be suspected as the pathogen; radiographic findings are diagnostically not helpful; FB is a sensitive diagnostic test for tuberculosis and in smear-negative cases where tuberculosis is suspected, initiation of empiric anti-tuberculosis therapy should be considered while awaiting culture results. .A Chan JC; So SY; Lam WK; Ip MS. .I 200880 .U 90004532 .S Chest 9001; 96(4):840-2 .M Adult; Aged; Comparative Study; Coronary Disease/*DI; Coronary Vessels/RA; Electrocardiography/*; Exercise Test/*MT; Female; Heart/RI; Human; Jogging/*; Male; Middle Age; Thallium Radioisotopes/DU. .T Jogging in place. Evaluation of a simplified exercise test. .P JOURNAL ARTICLE. .W The purpose of this study was to evaluate jogging in place as an electrocardiographic exercise test. Jogging in place continuously recorded via an ordinary single-channel electrocardiograph was compared with the Bruce treadmill protocol with a three-channel monitor and recorder in 141 cases with a wide spectrum of chest complaints. Agreement for the presence or absence of electrocardiographic ischemia (ST-segment displacement greater than or equal to 1 mm at 80 ms from the J point, or U-wave inversion) for the two tests was observed in 91 percent of the cases (95 percent confidence intervals: 86 percent to 95.5 percent). One hundred of the previous cases with paired electrocardiographic exercise tests were compared with the presence of reversible defects on exercise myocardial thallium-201 scintigraphy. The electrocardiographic ischemia had a similar correct classification rate in both methods (83 percent with jogging in place and 85 percent with Bruce treadmill protocol; not significant) against the finding of scintigraphic ischemia. This was also true for 52 cases having selective coronary arteriography. The correct classification rate was 54 percent (28/52) with jogging in place and 48 percent (25/52) with Bruce treadmill protocol (not significant). Given the safety and the easy applicability, even in older persons, this simplified test can be recommended as a valid alternative to the established multistage exercise tests. .A Papazoglou N; Kolokouri-Dervou E; Fanourakis I; Natsis P; Koutsiouba P. .I 200881 .U 90004533 .S Chest 9001; 96(4):843-8 .M Adolescence; Adult; Angiography; Arteriovenous Fistula/DI/*ET; Child; Cyanosis/ET; Diagnosis, Differential; Echocardiography; Female; Heart Catheterization; Heart Defects, Congenital/*DI; Human; Liver Cirrhosis/CO/*DI; Male; Pulmonary Artery/*; Pulmonary Veins/*. .T Cirrhosis of the liver simulating congenital cyanotic heart disease. .P JOURNAL ARTICLE. .W During the last 25 years, 20 patients with cirrhosis of liver with severe cyanosis and gross clubbing simulating congenital cyanotic heart disease were subjected to cardiac catheterization and angiography, splenography, liver function tests, and liver biopsy. No portopulmonary fistulas could be demonstrated. The cyanosis and clubbing were secondary to right to left intrapulmonary shunting across multiple tiny pulmonary arteriovenous fistulas. In 15 cases, selective pulmonary angiography revealed discrete arteriovenous fistulas. In five cases, the angiogram did not reveal any convincing evidence of pulmonary arteriovenous fistulas. In two of these five cases, peripheral vein contrast echocardiography demonstrated right to left intrapulmonary shunting and seems a sensitive investigation. Open lung biopsy in one case showed evidence of pulmonary arteriovenous fistulas. .A Hansoti RC; Sharma S. .I 200882 .U 90004535 .S Chest 9001; 96(4):852-6 .M Adult; Antidepressive Agents, Tricyclic/*PO; Charcoal/TU; Female; Human; Intensive Care Units; Lung Diseases/*CI/TH; Male; Middle Age; Overdose/TH; Pneumonia, Aspiration/CI; Respiration, Artificial; Suicide, Attempted. .T Pulmonary complications after tricyclic antidepressant overdose. .P JOURNAL ARTICLE. .W We studied 82 consecutive patients admitted to the ICU with predominant tricyclic antidepressant overdose (mean plasma tricyclic level, 1,025 ng/ml) to determine the nature and incidence of respiratory complications. The majority of patients (80.4 percent) had a decreased arterial to alveolar oxygen tension ratio (PaO2/PAO2) on initial emergency room arterial blood gas analysis (mean, 0.56). Mechanical ventilation was required in 76.8 percent of the patients for a mean duration of 46.2 h. Chest radiograph abnormalities developed during the first 48 h in 32/82 patients (39 percent). The group with radiographic abnormalities had higher mean drug levels than the group without (p less than 0.05). Of 82 patients, nine (11 percent) developed radiographic evidence of bilateral alveolar infiltrates suggestive of acute lung injury. This group had significantly higher mean drug levels than the groups with other types of radiographic abnormalities (p less than 0.001). Charcoal was recovered from the airway of 18/72 patients who received activated charcoal slurry by nasogastric tube in the emergency room after endotracheal intubation. The group who aspirated did not show statistically significant difference in the incidence of chest radiograph abnormalities, gas exchange, or survival compared with the group that did not aspirate. .A Roy TM; Ossorio MA; Cipolla LM; Fields CL; Snider HL; Anderson WH. .I 200883 .U 90004536 .S Chest 9001; 96(4):857-61 .M Acquired Immunodeficiency Syndrome/CO/*MO; Human; Intensive Care Units/*; Patient Admission; Pneumonia, Pneumocystis carinii/CO/MO; Prognosis; Regression Analysis; Severity of Illness Index/*; Survival Analysis. .T Prognosis of patients with AIDS requiring intensive care. .P JOURNAL ARTICLE. .W The Acute Physiology and Chronic Health Evaluation (APACHE) II classification, a measure of severity of illness in patients requiring intensive care, was devised before the rapid expansion of the acquired immunodeficiency syndrome (AIDS) epidemic. To determine the applicability of the APACHE II system to AIDS, we related observed in-hospital death rates to those predicted by APACHE II in 83 patients with AIDS. In a control group of patients without AIDS (n = 166) mean predicted and observed death rates (34.1 vs 31.3 percent) were similar. For the AIDS group overall observed mortality (63.9 percent) was significantly greater than that predicted by APACHE II (45.8 percent). The subgroup with Pneumocystis pneumonia requiring mechanical ventilation (n = 37) had an observed mortality (86.5 percent) that significantly exceeded the predicted value (44.3 percent), whereas all other AIDS patients (n = 46) showed similar predicted and observed death rates (47.0 vs 45.7 percent). APACHE II prediction of death rate also matched observed mortality in mechanically ventilated patients without Pneumocystis infection. The discrepancy between predicted and observed mortality in patients with Pneumocystis pneumonia requiring mechanical ventilation is most likely due to the lack of an APACHE II diagnostic category that accurately reflects the severity of this disease. A new diagnostic category that provides accurate outcome prediction in this patient group would form a basis for evaluation of new therapeutic interventions. .A Smith RL; Levine SM; Lewis ML. .I 200884 .U 90004539 .S Chest 9001; 96(4):873-6 .M Aged; Comparative Study; Coronary Artery Bypass/*MT; Follow-Up Studies; Human; Internal Mammary-Coronary Artery Anastomosis; Intraoperative Period; Lung Volume Measurements; Middle Age; Postoperative Complications/*PP; Respiratory Mechanics/*; Saphenous Vein/*TR; Sternum/*SU; Support, Non-U.S. Gov't. .T Effect of sternotomy and coronary bypass surgery on postoperative pulmonary mechanics. Comparison of internal mammary and saphenous vein bypass grafts. .P JOURNAL ARTICLE. .W Coronary artery bypass grafting (CABG) is commonly performed via a median sternotomy with a reversed saphenous vein (SV) and/or an internal mammary artery (IMA) graft. Sternotomy and IMA harvesting may adversely affect postoperative respiratory function (PFTs) as disruption of the sternun may impair chest wall stability, and the decrease in intercostal muscle blood supply after removal of the IMA may reduce the force of respiration. We compared preoperative and six- to eight-week postoperative PFTs in patients undergoing CABG. The results were independent of age, sex, number of grafts, aortic cross clamp time, duration of bypass run, and postbypass fluid gradient. It was concluded that sternotomy caused a decrease in postoperative PFTs and that IMA harvesting may be accompanied by greater impairment in PFTs than when SV grafts alone were used. .A Berrizbeitia LD; Tessler S; Jacobowitz IJ; Kaplan P; Budzilowicz L; Cunningham JN. .I 200885 .U 90004540 .S Chest 9001; 96(4):877-84 .M Hoarseness/ET; Human; Intubation, Intratracheal/*AE; Laryngeal Diseases/*ET; Laryngeal Edema/*ET; Laryngeal Mucosa/IN; Laryngoscopy; Male; Middle Age; Prospective Studies; Time Factors; Ulcer/ET; Vocal Cords/IN. .T Laryngeal complications of prolonged intubation [see comments] .P JOURNAL ARTICLE. .W In this study, 82 patients who experienced translaryngeal intubation (TLI) for more than four days were prospectively evaluated for laryngeal complications. At the time of extubation or tracheostomy, direct laryngoscopy was performed in these patients and laryngeal damage evaluated. A typical pattern of laryngeal damage was seen, consisting of mucosal ulcerations along the posterior-medial aspects of both vocal cords and varying degrees of laryngeal edema in 77 patients (94 percent). Performance of a tracheostomy and presence of neuromotor activity were associated with the severity of laryngeal damage, but duration of TLI was not. Laryngoscopy was repeated at two-week intervals in 54 patients and laryngeal damage was resolved within four weeks in 63 percent. These 54 patients were evaluated for adverse clinical effects arising from TLI-induced laryngeal pathology and no relationship was found between laryngeal pathology seen at initial laryngoscopy and the development of adverse effects. .A Colice GL; Stukel TA; Dain B. .I 200886 .U 90004545 .S Chest 9001; 96(4):915-6 .M Adult; Case Report; Ethiodized Oils/*AE; Hemorrhage/*CI; Human; Lung/*RA; Lung Diseases/*CI/RA; Lymphography/*AE; Male. .T Diffuse pulmonary infiltrates following lymphography. .P JOURNAL ARTICLE. .A Tapper DP; Taylor JR. .I 200887 .U 90004546 .S Chest 9001; 96(4):917-8 .M Adult; Case Report; Human; Male; Ribs/*AB/RA; Thoracic Radiography. .T Adam's antipole. .P JOURNAL ARTICLE. .A Links TP; Postmus PE. .I 200888 .U 90004548 .S Chest 9001; 96(4):922-3 .M Ascariasis/*CO; Case Report; Heart Arrest/*ET; Heart Surgery; Human; Intubation, Intratracheal/*; Male; Middle Age; Postoperative Complications/*ET. .T Cardiac arrest postoperatively in a patient infected with ascaris, the roundworm. .P JOURNAL ARTICLE. .A Nicholson JP; Kreiger K; Hartman B; Isom W; Laragh JH. .I 200889 .U 90004549 .S Chest 9001; 96(4):924-6 .M Abscess/*ET; Actinomycosis/*DI; Aged; Case Report; Female; Human; Sternum/*; Thoracic Diseases/*DI. .T A red hot sternal mass. .P JOURNAL ARTICLE. .A McCarty MJ; Whitlock WL; Dietrich RA. .I 200890 .U 90004550 .S Chest 9001; 96(4):927-8 .M Aged; Biopsy; Capillaries/PA; Case Report; Female; Hemorrhage/*ET; Human; Lung/BS; Lung Diseases/*ET; Necrosis; Periarteritis Nodosa/*CO/DI; Support, U.S. Gov't, P.H.S.. .T Pulmonary capillaritis and hemorrhage. A clue to the diagnosis of systemic necrotizing vasculitis. .P JOURNAL ARTICLE. .W Patients with systemic necrotizing vasculitis frequently present as diagnostic dilemmas. In previous series of patients with polyarteritis nodosa, less than one third were diagnosed antemortem. Although current clinical awareness of systemic necrotizing vasculitis is greater than in the past and procedures for the diagnosis of these diseases have improved, patients commonly present with atypical features. The diagnosis of a systemic necrotizing vasculitis frequently remains unsuspected or unproven until an involved tissue is biopsied. We report an unusual case of systemic necrotizing vasculitis in which the diagnosis was confirmed by a transbronchial biopsy of the lung which demonstrated pulmonary capillaritis with hemorrhage. .A Imoto EM; Lombard CM; Sachs DP. .I 200891 .U 90004552 .S Chest 9001; 96(4):931-3 .M Adult; Case Report; Female; Follow-Up Studies; Human; Lung/PA; Lung Diseases/*ET/PA; Sarcoidosis/*CO/PA; Stomach Diseases/*CO; Support, Non-U.S. Gov't; Time Factors. .T From subclinical alveolitis to granulomatosis. Sequential evaluation of pulmonary involvement in extrathoracic sarcoidosis. .P JOURNAL ARTICLE. .W Follow-up of patients with subclinical inflammatory alveolitis associated with systemic diseases may represent the best opportunity to study the mechanisms responsible for the development of interstitial lung disease. We report a seven-year sequential pulmonary evaluation of one patient with clinically isolated gastric sarcoidosis, treated by gastrectomy, without evidence of clinical, radiologic or functional lung impairment and with chronic subclinical lymphocyte alveolitis. Five years later, she developed an overt interstitial lung disease characterized by fine crackles, diffuse parenchymal opacities and impaired diffusing capacity, preceded by an expansion of polymorphonuclear neutrophils in the lower respiratory tract, raising the hypothesis that these cells may be implicated in the pathogenesis of pulmonary derangement in sarcoidosis. This observation illustrates the importance of pulmonary follow-up of unaffected patients with systemic diseases and with subclinical inflammatory alveolitis, and the potential predictive value of neutrophil alveolitis in the pulmonary outcome of these patients. .A Dugas M; Wallaert B; Tonnel AB; Voisin C. .I 200892 .U 90004553 .S Chest 9001; 96(4):934-5 .M Adenocarcinoma/DI/SC; Carcinoma, Squamous Cell/DI/SC; Case Report; Echocardiography/*; Esophageal Neoplasms/*PA; Female; Heart Neoplasms/DI/*SC; Human; Male; Middle Age. .T Endomyocardial invasion by esophageal carcinoma. Demonstration by echocardiography. .P JOURNAL ARTICLE. .W Two cases of esophageal carcinoma with echocardiographically demonstrable direct extension are presented. Recognition of esophageal carcinoma metastatic to the heart is clinically difficult but can be facilitated by two-dimensional echocardiography. Earlier recognition of cardiac metastases by echocardiography may allow more effective therapy. .A Brodell GK; Schiavone WA; Finkelhor R. .I 200893 .U 90004555 .S Chest 9001; 96(4):937-9 .M Adolescence; Angiography; Case Report; Echocardiography; Female; Heart Atrium/*AB; Heart Defects, Congenital/*DI; Human; Pulmonary Artery/*AB/RA. .T Direct communication between the left pulmonary artery and the left atrium. .P JOURNAL ARTICLE. .W A 17-year-old patient was found to have cyanosis. A right-to-left shunt was suspected clinically and confirmed by noninvasive techniques such as perfusion lung scan and contrast echocardiography. Angiography showed this shunt to be between the left pulmonary artery and the left atrium. We believe this to be the first report of a hitherto undescribed congenital anomaly. .A Karnik AM; Nilsson U; Vijayaraghavan G; Hashmi J; Shuhaiber H. .I 200894 .U 90004557 .S Chest 9001; 96(4):941-3 .M Body Temperature/*; Catheterization, Swan-Ganz/*IS; Equipment Failure; Human; Intensive Care Units; Monitoring, Physiologic/IS; Reference Standards; Thermometers/*ST. .T Evaluation of an inaccurate pulmonary artery catheter thermistor. .P JOURNAL ARTICLE. .W A previously undescribed complication involving PAC thermistor temperature readings is characterized in this study. The thermistor readings became falsely elevated after the PAC was immersed in water, increasing steadily to 17.6 degrees C above control temperature readings. The abnormality resolved when the PAC was removed from immersion. A survey of ICUs revealed that PAC thermistors are frequently used to monitor the body temperature of patients requiring PACs. Only seven (35 percent) of 20 surveyed ICUs using PAC thermistors routinely confirmed PAC estimates of body temperature with another thermometric device. Since erroneous temperature measurements can have profoundly deleterious effects on clinical management, routine validation of PAC thermistors should be considered. .A Gotchall JI; Comried L; Bredlau G; Moseley PL. .I 200895 .U 90004559 .S Chest 9001; 96(4):945-6 .M Aged; Case Report; Coronary Disease/*CO; Fistula/*CO; Heart Atrium; Heart Block/CO; Heart Neoplasms/BS/*CO/SU; Human; Male; Mitral Valve Insufficiency/*CO; Myxoma/BS/*CO/SU. .T Myxoma with a left-to-left shunt and fistula. .P JOURNAL ARTICLE. .W We present the case of a 68-year-old man with a peculiar coincidence of cardiac pathologic findings: a huge left atrial myxoma, mitral insufficiency, a high degree atrioventricular block and three-vessel disease. The myxoma was vascularized from a dilated sinus arteriosus branch, giving rise to neovascularization at the base of the tumor. Blood from the neovascularization gathered into a large cavern which fistulated into the left atrium, responsible for a left-to-left cardiac shunt. .A Jorens PG; Van Den Heuvel PA; Van Cauwelaert PA; Parizel GA. .I 200896 .U 90004560 .S Chest 9001; 96(4):946-8 .M Abscess/ET/*TH; Adult; Ampicillin/TU; Case Report; Drainage/*MT; Human; Male; Mediastinal Diseases/ET/*TH; Tracheostomy/*AE. .T Successful novel drainage treatment of mediastinal abscess complicating tracheostomy. .P JOURNAL ARTICLE. .W Drainage from an old tracheostomy stoma with occurrence of fever and chills in a patient led to the discovery of a mediastinal abscess behind the anterior chest wall, an unusual complication of tracheostomy. Successful treatment consisted of intravenous administration of an antibiotic and repeated aspiration of the abscess through a plastic tube inserted into the old tracheostomy stoma. .A Watanakunakorn C. .I 200897 .U 90004561 .S Chest 9001; 96(4):948-9 .M Adult; Biopsy/MT; Bronchi/*PA; Bronchoscopy/MT; Case Report; Hodgkin's Disease/*PA; Human; Lung Neoplasms/*PA; Male. .T Cytologic diagnosis of pulmonary Hodgkin's disease via endobronchial brush preparation [see comments] .P JOURNAL ARTICLE. .W A case is presented where a young man who was treated for Hodgkin's disease presented with a new pulmonary infiltrate. The infiltrate was diagnosed as recurrent Hodgkin's disease by means of endobronchial brush cytology via fiberoptic bronchoscopy. .A Rubin AH; Ben-Shachar M; Malberger E. .I 200898 .U 90004562 .S Chest 9001; 96(4):949-51 .M Acquired Immunodeficiency Syndrome/*CO; Adult; Aerosols; Case Report; Choroiditis/*ET; Hepatitis/*ET; Human; Male; Opportunistic Infections/CO/*PC; Pentamidine/*AD/TU; Pneumocystis carinii/IP; Pneumonia, Pneumocystis carinii/CO/*PC. .T Pneumocystis hepatitis and choroiditis despite successful aerosolized pentamidine pulmonary prophylaxis. .P JOURNAL ARTICLE. .W A patient who developed Pneumocystis carinii hepatitis and choroiditis despite receiving prophylactic pentamidine therapy by aerosol is described. Liver biopsy showed histology typical of Pneumocystis hepatitis, but his respiratory status was stable and his lungs were free of P carinii organisms on BAL. Thus, inhaled pentamidine prophylaxis did not prevent extrapulmonary pneumocystosis. Patients receiving pentamidine prophylaxis with unexplained symptoms should undergo investigation for possible extrapulmonary P carinii infection. .A Hagopian WA; Huseby JS. .I 200899 .U 90004563 .S Chest 9001; 96(4):952 .M Asbestosis/*RA; Human. .T X-ray films and asbestosis [letter; comment] .P COMMENT; LETTER. .A David A. .I 200900 .U 90004564 .S Chest 9001; 96(4):953 .M Blood Gas Analysis/*; Human; Pulmonary Embolism/*BL. .T Sensitivity of arterial blood gas analyses [letter; comment] [see comments] .P COMMENT; LETTER. .A Kufs WM. .I 200901 .U 90004565 .S Chest 9001; 96(4):953-5 .M Asthma/*DT; Bronchodilator Agents/*AD; Human; Length of Stay/*; Nebulizers and Vaporizers. .T Discharging of asthma patients [letter; comment] .P COMMENT; LETTER. .I 200902 .U 90004566 .S Chest 9001; 96(4):955-6 .M Human; Thoracic Vertebrae/*; Tuberculosis, Spinal/*SU. .T Pott's disease [letter; comment] .P COMMENT; LETTER. .I 200903 .U 90004569 .S Chest 9001; 96(4):957-8 .M Animal; Human; Lung Diseases, Parasitic/*TM; Paragonimiasis/*TM; Swine/*PS. .T Wild boars and pulmonary paragonimiasis [letter] .P LETTER. .A Kawane H. .I 200904 .U 90004570 .S Chest 9001; 96(4):958-9 .M Aged; Case Report; Electrocardiography; Human; Male; Pulmonary Emphysema/CO; Tachycardia/*CI/DT; Theophylline/*AE; Verapamil/*TU. .T Theophylline-induced ventricular tachycardia in a patient with chronic lung disease. Sensitivity to verapamil [letter] .P LETTER. .A Taniguchi A; Ohe T; Shimorura K. .I 200905 .U 90004572 .S Chest 9001; 96(4):959 .M Human; Intubation, Intratracheal/*AE; Trachea/*IN. .T Tracheal trauma [letter] .P LETTER. .A Katlic MR. .I 200906 .U 90004573 .S Chest 9001; 96(4):959-60 .M Cryosurgery/*; Electrocoagulation/*; Human; Laser Surgery/*. .T Cryosurgery, electrocautery and the laser [letter; comment] .P COMMENT; LETTER. .I 200907 .U 90004574 .S Chest 9001; 96(4):960-1 .M Antibodies, Antinuclear/*AN; Human; Lung Diseases/*DI/ET; Respiratory Function Tests; Scleroderma, Systemic/*CO; Serodiagnosis. .T Antinuclear antibodies associated with pulmonary involvement in systemic sclerosis [letter] .P LETTER. .A Martinez-Cordero E. .I 200908 .U 90004575 .S Chest 9001; 96(4):961-2 .M Aged; Homes for the Aged/*; Human; Mass Screening/*; New York City/EP; Nursing Homes/*; Tuberculosis, Pulmonary/*PC. .T Tuberculosis screening in 1,161 elderly patients [letter] .P LETTER. .A Aronow WS; Bloom HG. .I 200909 .U 90004728 .S Dis Colon Rectum 9001; 32(10):825-8 .M Adult; Crohn Disease/*CO; Female; Human; Methods; Middle Age; Rectovaginal Fistula/ET/*SU. .T Rectovaginal fistula in Crohn's disease. .P JOURNAL ARTICLE. .W Rectovaginal fistulas in the setting of Crohn's disease present a difficult management dilemma. Some patients with this problem require proctocolectomy, yet other patients with minimal symptoms never require an operation for treatment of the rectovaginal fistula. For a small percentage of patients, local surgical repair of the fistula may be warranted. Since 1980, this study has attempted local repair in seven patients with symptomatic rectovaginal fistulas from Crohn's disease. Five patients underwent staged repair of the fistula. Closure of the colostomy was eventually possible in three of these patients. Two of the three patients have had no evidence of recurrence at followup in excess of two years. The third patient required an ileostomy for intestinal disease and had no recurrence of the fistula. Two patients underwent primary repair of the rectovaginal fistula without fecal diversion; in one of these patients, the fistula recurred ten days after operation, necessitating a diverting ileostomy. The other patient remains cured 26 months after repair. The results of this review indicate that in the setting of quiescent rectal disease, an attempt to repair the fistula can be expected to have a reasonable chance of success. The presence of a rectovaginal fistula in a patient with Crohn's disease does not mandate removal of the rectum. .A Cohen JL; Stricker JW; Schoetz DJ Jr; Coller JA; Veidenheimer MC. .I 200910 .U 90004729 .S Dis Colon Rectum 9001; 32(10):829-34 .M Adenoma/PA/SU; Adult; Aged; Aged, 80 and over; Carcinoma/PA/*SU; Colonic Neoplasms/PA/*SU; Colonic Polyps/PA/SU; Colonoscopy/*; Female; Human; Intestinal Polyps/PA/*SU; Male; Methods; Middle Age; Neoplasm Recurrence, Local; Rectal Neoplasms/PA/*SU; Reoperation. .T Management of patients with invasive carcinoma removed by colonoscopic polypectomy. .P JOURNAL ARTICLE. .W The management of patients with invasive carcinoma removed by colonoscopic polypectomy remains controversial. In order to assess the criteria for subsequent surgery after polypectomy, the histologic findings and outcome of 25 patients with invasive carcinomas treated by polypectomy were analyzed. Subsequent surgery was indicated when removed invasive carcinoma showed at least one of the following findings: 1) carcinoma near the surgical margin, 2) vessel invasion, 3) massive invasion, and 4) poorly differentiated adenocarcinoma. The authors considered those findings to be a risk factor for local residual carcinoma or lymph-node metastases, or both. Of 25 patients, 18 showed risk factors, with 16 receiving surgery. Only one had residual carcinoma in the lymphatic vessel of the surgical specimen. The remaining 15 had no carcinoma in the surgical specimens, however, one died of recurrent disease 55 months later. Two patients with risk factors received no surgery for various reasons. Local recurrent carcinoma developed in one 39 months later and the other had no recurrent carcinoma at autopsy. Seven patients without risk factors were adequately treated by polypectomy without recurrent disease 34 to 96 months later (average, 69 months). Consequently, of 18 patients with risk factors, 3 showed either residual carcinoma in the surgical specimens or recurrent carcinoma was found later. None of 7 patients without risk factors developed recurrent disease. We recommend that patients with risk factors be followed by surgery; however, patients without risk factors can be adequately treated by polypectomy alone. .A Sugihara K; Muto T; Morioka Y. .I 200911 .U 90004730 .S Dis Colon Rectum 9001; 32(10):835-8 .M Adolescence; Adult; Aged; Aged, 80 and over; Anus/PP; Constipation/ET; Fecal Incontinence/ET; Female; Human; Male; Methods; Middle Age; Postoperative Complications; Pressure; Rectal Prolapse/CO/PP/*SU; Rectum/*SU; Recurrence; Reoperation; Surgical Mesh. .T Functional results after posterior abdominal rectopexy for rectal prolapse. .P JOURNAL ARTICLE. .W One hundred sixty-five cases of abdominal rectopexy using polypropylene (Marlex) mesh for rectal prolapse were reviewed. Six patients were men and 159 were women. Thirty patients have not been evaluated after surgery, 22 having died of interrecurrent disease and 8 have had their surgery during the last two months. Incontinence was observed in 95 patients (58 per cent) before surgery, whereas it persisted in only 21 of 135 patients (16 percent) after surgery. Forty patients (24 percent) claimed constipation before surgery, whereas 60 of 135 patients (44 percent) had constipation after rectopexy. Recurrence of full-thickness rectal prolapse was found in only 2 patients-(1.5 percent). Mucosal prolapse occurred in 9 patients (7 percent) after surgery. These results indicate that abdominal posterior rectopexy using Marlex mesh is an effective operation for rectal prolapse, but persistent incontinence occurs in one third of patients and almost half become constipated after the procedure. .A Yoshioka K; Heyen F; Keighley MR. .I 200912 .U 90004731 .S Dis Colon Rectum 9001; 32(10):839-42 .M Adolescence; Adult; Aged; Anus/*PP; Chronic Disease; Female; Fissure in Ano/*PP; Hemorrhoids/*PP; Human; Male; Manometry; Middle Age; Pressure. .T Anal manometric studies in hemorrhoids and anal fissures. .P JOURNAL ARTICLE. .W Manometric study with the use of continuous water perfusion system was performed on 50 patients with Grade III or IV hemorrhoids and for 29 patients with chronic anal fissure. Another 36 patients who had no anorectal symptoms or pathology were chosen as the control group. The maximal basal pressures for the controls, hemorrhoids, and chronic anal fissures were 71.2 +/- 24.9, 85.3 +/- 27.7, and 87.4 +/- 38.8 mmHg, respectively; the maximal contraction pressures for the controls, hemorrhoids, and fissures were 132.9 +/- 44.9, 158.8 +/- 58.0, and 162.1 +/- 64.5 mmHg, respectively; the lengths of the functional sphincter of the three groups were 3.7 +/- 0.5, 3.8 +/- 0.8, and 3.9 +/- 0.6 cm, respectively. The maximal basal pressures and maximal contraction pressures of the hemorrhoid and fissure patients were significantly greater than those of the control group (t test, P value less than 0.05); whereas the functional sphincter lengths of the three groups showed no significant difference. .A Lin JK. .I 200913 .U 90004732 .S Dis Colon Rectum 9001; 32(10):843-6 .M Adenocarcinoma/*/MO/PA/TH; Adolescence; Adult; Age Factors; Child; Colorectal Neoplasms/*/MO/PA/TH; Female; Human; Male; Prognosis; Survival Rate. .T Colorectal cancer in patients younger than 40 years of age. .P JOURNAL ARTICLE. .W To assess prognostic factors in patients who develop colorectal cancer before the age of 40 years, a 30-year experience from 1956 through 1985 was reviewed. There were 50 patients ranging in age from 7 to 39 years. Five cases were associated with either ulcerative colitis (2) or familial polyposis (3). The most common presenting symptoms were abdominal pain (66 percent), hematochezia (60 percent), change in bowel habit (41 percent) and weight loss (30 percent). On pathologic staging (N = 44), only 14 of 44 (31 percent) had a Dukes' stage A or B lesion, 20 (45 percent) had Dukes' stage C, and the remaining 10 (23 percent) had distant metastases at the time of surgery. Five-year survival rate was 28 percent with a disease-free survival rate of 18 percent. Median survival was only 28 months. Negative prognostic factors were Dukes' stage C/D (P less than .001), symptom duration of longer than 3 months (P = .01), noncaucasian ancestry (P = .01), and poorly differentiated histology (P = .06). In contrast to older patients with colorectal cancer, only 1 of 30 (3 percent) patients with stage C D disease was disease-free at 5 years. In view of the poor survival rate associated with both delay in diagnosis and the presence of advanced disease, it was concluded that young patients presenting with the symptoms listed above need early, aggressive evaluation for possible colorectal cancer. .A Smith C; Butler JA. .I 200914 .U 90004733 .S Dis Colon Rectum 9001; 32(10):847-8 .M Adolescence; Adult; Aged; Crohn Disease/*CO/PA; Female; Human; Male; Methods; Middle Age; Rectal Fistula/ET/PA/*SU. .T Experience with perirectal fistulas in patients with Crohn's disease. .P JOURNAL ARTICLE. .W The experience of the senior author has been reviewed in dealing with perianal fistulas in patients with Crohn's disease. Early surgical therapy was advocated, the theory being, that perianal fistulas start as intersphincteric fistulas. This fistula is easily controlled surgically by fistulotomy with partial internal and sphincterotomy. Delay in surgical treatment, especially in Crohn's patients, results in more complicated fistulas that may require colostomy or proctectomy. The presence of Crohn's disease did not affect the healing of fistulotomy. In our series fistulotomy was the treatment of choice in patients with 26 fistulas; 18 of 19 went on to full healing. We conclude that early fistulotomy, before an intersphincteric fistula has time to blossom into a more difficult management problem, is the treatment of choice in patients with Crohn's disease who have perianal fistulas. .A Fuhrman GM; Larach SW. .I 200915 .U 90004734 .S Dis Colon Rectum 9001; 32(10):849-54 .M Aged; Aged, 80 and over; Diverticulosis, Colonic/CO/MO/*SU; Emergencies; Human; Intestinal Perforation/ET; Methods; Middle Age; Peritonitis/ET; Postoperative Complications. .T Emergency surgery for complicated diverticular disease. A five-year experience. .P JOURNAL ARTICLE. .W Ninety-three patients who underwent surgery were studied retrospectively over a five-year period for complications of diverticular disease, including free perforation in 32 patients (with fecal peritonitis in 8), inflammation or peritonitis in 22 patients, an abscess in 11 patients, and intestinal obstruction in 14 patients. Sixty-eight patients (73 percent) had systemic symptoms and signs consistent with serious sepsis. There has been a growing popularity of the Hartmann procedure throughout the study period. The overall 30-day mortality rate was 10.8 percent. Because of a high proportion of poor-risk patients, the Hartmann group fared particularly badly compared with those who had other operations, with a 28 percent mortality rate, 69 percent incidence of major complications, and one third of the survivors having a permanent colostomy. Other operative procedures are discussed, but until prospective data become available, it is unlikely that the widespread popularity of the Hartmann procedure will decline. Therefore, the importance of meticulous attention to technical detail is stressed if results are to improve. .A Berry AR; Turner WH; Mortensen NJ; Kettlewell MG. .I 200916 .U 90004736 .S Dis Colon Rectum 9001; 32(10):860-3 .M Animal; Bile Acids and Salts/*ME/PH; Carcinogens; Colonic Neoplasms/CI/*ET/ME/SU; Dimethylhydrazines; Feces/*AN; Intestines/SU; Male; Rats; Rats, Inbred Strains. .T Effect of change of fecal bile acid excretion achieved by operative procedures on 1,2-dimethylhydrazine-induced colon cancer in rats. .P JOURNAL ARTICLE. .W The effect of bile on the development of 1,2-dimethylhydrazine (DMH)-induced colon cancer was studied in male Wistar rats. Experimental operative models were created, in which in Group 1, the half intestinal tract, the ileum, and the right side of colon were released from bile. In Group 2, both sides of the colon contained bile. The sham operated animals formed Group 3. These techniques changed the concentration of bile acid in different parts of the colon, and the daily total fecal bile acid excretion as well. After DMH treatment, the relationship between these changes of bile acid level and the development of colon cancer was studied. Significantly more tumors than in the control group were found if the daily total bile acid level and the bile acid concentration in the left side of the colon were increased. Our findings show an unambiguous connection between the fecal bile acid level and the incidence of DMH-induced colon cancer. .A Morvay K; Szentleleki K; Torok G; Pinter A; Borzsonyi M; Nawroth R. .I 200917 .U 90004737 .S Dis Colon Rectum 9001; 32(10):864-6 .M Aged; Aged, 80 and over; Case Report; Colon/*SU; Colonic Polyps/SU; Colonoscopy/*/MT; Human; Intraoperative Period; Middle Age. .T Clean sweep of the colon. The use of intraoperative colonoscopy. .P JOURNAL ARTICLE. .W Since 1982, intraoperative colonoscopy has been performed on 66 patients. Preoperative intent was to perform a colonoscopic polypectomy during an intra-abdominal procedure in 44 patients, localize lesions that might subsequently lead to either colon resection or colotomy and polyp excision in 13, localize bleeding sites in 4, determine the extent of inflammatory bowel disease in 2, survey the colon in 2 who did not have preoperative colon radiography, and assess bowel viability in 1. Surgery proceeded as planned in 54 patients; however, colonoscopic findings extended the resection to include additional segments of bowel in 4. In four patients, polypectomy or bowel resection was avoided as a result of the colonoscopic findings. Intraoperative colonoscopy was not possible in four patients. No complications were related directly to this procedure. Intraoperative colonoscopy is a useful adjunct for localizing lesions or "clearing" the colon. In some patients, colonoscopic findings may change the extent of resection performed. .A Saclarides TJ; Wolff BG; Pemberton JH; Devine RM; Nivatvongs S; Dozois RR. .I 200918 .U 90004739 .S Dis Colon Rectum 9001; 32(10):871-7 .M Adenocarcinoma/CI/PA; Animal; Biological Products/*PD; Carcinoma, Mucinous/CI/PA; Intestinal Neoplasms/CI/*PA; Male; Methylnitrosourea; Picibanil/*PD; Rats; Rats, Inbred Strains; Time Factors. .T Effect of OK-432 on large-bowel carcinogenesis in rats. .P JOURNAL ARTICLE. .W To examine the carcinogenetic and growth inhibitory effects of OK-432, large-bowel carcinoma was induced experimentally in rats by intrarectal injection of N-methyl-N-nitrosourea (MNU), and OK-432 was administered intradermally. Rats were sacrificed after six months and the large intestine was cut into serial sections. Histopathologic examination and analysis of the infiltrating mononuclear cells, using monoclonal antibodies, were performed. The average rate of carcinogenesis per rat was 15.7 +/- 8.5 in the MNU alone group (n = 10) and 8.3 +/- 3.5 in the MNU and OK-432 group (n = 6). The invasion was deeper than the muscularis propria in 16 out of 157 lesions (10.2 percent) in the MNU alone group and in one out of 50 lesions in the MNU + OK-432 group (2.0 percent) (P less than 0.05). When time of appearance of atypical glands or carcinomas were compared in the MNU alone and MNU + OK-432 group, carcinogenesis was found to be delayed in the MNU + OK-432 group. In the investigation of infiltrating mononuclear cells using monoclonal antibodies, there were increases in helper T cells in both the MNU alone and MNU + OK-432 groups, but there was little difference between the two groups. The results of this study suggest that the suppression of experimental carcinogenesis in the large bowel by the concomitant administration of OK-432 with MNU, may be due to the enhanced activation or prolonged activated state of immunocompetent cells, which appear via antigen recognition, by OK-432. .A Morodomi T; Isomoto H; Shirouzu G; Shirouzu K; Kakegawa T; Irie K; Morimatsu M. .I 200919 .U 90004742 .S Dis Colon Rectum 9001; 32(10):888-92 .M Adult; Case Report; Colonic Diseases/ET/SU; Crohn Disease/*CO/SU; Female; Gastric Fistula/*ET/SU; Human; Ileal Diseases/ET/SU; Intestinal Fistula/ET/SU; Male; Middle Age. .T Gastric fistulas in Crohn's disease. Report of cases. .P JOURNAL ARTICLE. .W Nine cases of gastric fistula occurring in patients with Crohn's disease were treated at The Mount Sinai Hospital over the past three decades. Six cases were found in a review of 1480 patients with Crohn's disease admitted between 1960 and 1983. Three others seen at this institution outside the time frame of the author's study have also been included. Among six new cases, five with cologastric fistula occurred among 907 patients with Crohn's disease involving the colon (0.6 percent), while only one with ileogastric fistula was encountered among 1211 patients with ileal disease (0.08 percent). Fistulas between the stomach and colon always originated in an area of colitis, usually passing from distal transverse colon to greater curvature, but occasionally from midtransverse colon to antrum. The only pathognomonic clinical features were feculent vomiting, eructations, or odor. Diagnosis usually was made by barium enema or, less frequently, by upper gastrointestinal series; rarely, the gastric fistula was found unexpectedly at surgery. The conventional and recommended therapy is colectomy with wedge excision of the stomach. Medical treatment with 6-mercaptopurine has been completely successful in one patient and intermittently successful in a second patient. .A Greenstein AJ; Present DH; Sachar DB; Slater G; Heimann T; Lachman P; Aufses AH Jr. .I 200920 .U 90004743 .S Dis Colon Rectum 9001; 32(10):893-6 .M Adenocarcinoma/CO/PA; Adolescence; Carcinoma, Papillary/CO/PA; Case Report; Female; Human; Hyperplasia; Liver/PA; Polyposis Syndrome, Familial/*CO; Thyroid Gland/PA; Thyroid Neoplasms/CO/PA; Thyroiditis/*CO/PA. .T Familial adenomatous polyposis in association with thyroiditis. Report of two cases. .P JOURNAL ARTICLE. .W The authors report two patients with familial adenomatous polyposis and thyroiditis. One patient was discovered at autopsy to have in addition, a follicular carcinoma of the thyroid and focal nodular hyperplasia of the liver. The other patient had a sister with familial adenomatous polyposis and a papillary carcinoma of the thyroid. The association between familial adenomatous polyposis and thyroiditis has not been previously reported. .A Herrera L; Carrel A; Rao U; Castillo N; Petrelli N. .I 200921 .U 90004744 .S Dis Colon Rectum 9001; 32(10):898-902 .M Human; Life Tables; Rectal Neoplasms/MO/SU; Survival Analysis/*; Survival Rate. .T Survival analysis: a practical approach. .P JOURNAL ARTICLE. .W Survival analysis is a statistical method used to calculate the probability of an event such as death or relapse of disease occurring in a patient over time. Survival analysis is important in the interpretation of clinical research, and is frequently encountered in the colorectal literature. In this article, the terminology used in survival analysis is explained, specific examples are presented, and common methods of calculation demonstrated. .A Reznick RK; Guest CB. .I 200922 .U 90004745 .S Dis Colon Rectum 9001; 32(10):904 .M Drainage/*MT; Human; Pelvis; Postoperative Care/*; Rectum/IN/*SU. .T Pelvic drainage [letter] .P LETTER. .A Miller JM. .I 200923 .U 90004746 .S Dis Colon Rectum 9001; 32(10):904-5 .M Case Report; Colonic Diseases/CO; Hernia, Diaphragmatic, Traumatic/CO; Human; Intestinal Fistula/*CO; Male; Middle Age; Pneumothorax/*ET; Rectal Fistula/CO. .T Colorectal fistula presenting as tension pneumothorax [letter] .P LETTER. .A Moritz E. .I 200924 .U 90004747 .S Dis Colon Rectum 9001; 32(10):905 .M Cecal Diseases/*DI; Crohn Disease/*DI; Diagnosis, Differential; Human; Ileal Diseases/*DI; Tuberculosis, Gastrointestinal/*DI. .T Differentiating tuberculosis from Crohn's disease of the small bowel [letter] .P LETTER. .A Shah P; Ramakantan R. .I 200925 .U 90004748 .S Dis Colon Rectum 9001; 32(6):457-65 .M Adult; Alopecia/*ET; Anastomosis, Surgical; Anus/*SU; Female; Human; Ileum/*SU; Male; Middle Age; Nutritional Status; Postoperative Complications/*; Prospective Studies; Retrospective Studies. .T Alopecia after ileal pouch-anal anastomosis. .P JOURNAL ARTICLE. .W Severe diffuse hair loss in a young woman after ileal pouch-anal anastomosis prompted a review of the incidence and cause of this complication. Nine (38 percent) of 24 patients undergoing the ileoanal pouch procedure developed hair loss. Clinically apparent hair loss is more likely in females. The cause is probably multifactorial and is unlikely to be related to specific nutritional deficiencies in patients maintaining oral intake of nutrients. Hair loss in the perioperative period is transient and hair growth returns to normal as the patient recovers. Awareness of this problem is important and reassurance of the concerned patient is the appropriate management. .A Thompson JS. .I 200926 .U 90004750 .S Dis Colon Rectum 9001; 32(6):466-8 .M Adult; Aged; Bacteria/IP; Candida/IP; Feces/*MI; Female; Human; Male; Middle Age; Pruritus Ani/*MI. .T The fecal microflora in pruritus ani. .P JOURNAL ARTICLE. .W Pruritus ani is a common condition in which there is a tendency for liquids to leak from the anal canal, resulting in perianal soiling. In order to ascertain if an abnormal fecal flora contributes to the irritant effects of fecal material, qualitative and quantitative measurement of the fecal microflora was performed in 20 patients with pruritus ani and 20 matched controls. No differences were found between the two groups. This study has failed to provide evidence for a microbiologic basis for pruritus ani. .A Silverman SH; Youngs DJ; Allan A; Ambrose NS; Keighley MR. .I 200927 .U 90004751 .S Dis Colon Rectum 9001; 32(6):469-72 .M Adolescence; Adult; Aged; Aged, 80 and over; Colitis/ET/*MO/PA/SU; Colon/*BS; Female; Human; Ischemia/*CO; Male; Middle Age; Retrospective Studies. .T Mortality from ischemic colitis. .P JOURNAL ARTICLE. .W Thirty-nine hospital-based cases of ischemic colitis were reviewed. There were 18 males and 21 females. Average age was 68.7 years (range, 18 to 92 years). Associated diseases among 13 patients younger than 65 included renal failure in seven patients and hematologic, vasculitic, or collagen vascular diseases in four. In 26 patients 65 or older, congestive heart failure was seen in 13, vascular disease in eight, and previous aortic surgery in four. Nineteen patients were treated nonsurgically and 8 died (42 percent mortality). Twenty patients (51 percent) underwent surgery: 18 had resection with colostomy or ileostomy and two had resection with reanastomosis; one patient underwent laparotomy followed by second-look exploration without resection. Thirteen of the 20 surgical patients died (65 percent mortality). Both patients who underwent reanastomosis died of sepsis. The data show a close association between ischemic colitis and a number of serious systemic diseases including renal failure, arteriosclerotic heart and vascular disease, and hematologic, vasculitic, and connective-tissue disease. A predilection for the right colon and sigmoid colon and splenic flexure was seen. A formidable mortality rate (53 percent) was found among patients treated both surgically and nonsurgically. .A Guttormson NL; Bubrick MP. .I 200928 .U 90004752 .S Dis Colon Rectum 9001; 32(6):473-6 .M Adult; Age Factors; Female; Human; Lymphatic Metastasis; Male; Neoplasm Recurrence, Local; Prognosis; Rectal Neoplasms/MO/PA/*SU; Risk Factors; Survival Rate. .T Clinical significance of rectal cancer in young patients. .P JOURNAL ARTICLE. .W Thirty-nine patients (age 40 years and younger) with rectal cancer treated at the Mount Sinai Hospital between 1967 and 1985 were studied. Their mean age was 34 years (range, 21 to 40). A positive family history for colorectal cancer was found in six patients (15 percent). Fifty percent of patients under age 30 had metastatic disease at diagnosis. Twenty-seven patients (69 percent) had potentially curative resections. Of these, 17 (63 percent) had lymph-node metastasis. This rate is twice as high as in a group of 315 patients with rectal cancer over age 40 (31 percent). The overall five-year survival for young patients having curative resection was 53 percent. Noncolorectal cancer occurred in three patients in this series and six patients also had first-degree relatives with noncolorectal cancer. Young patients with rectal cancer appear to belong to a high-risk cancer group which often seems to have a genetic pattern of predisposition. .A Heimann TM; Oh C; Aufses AH Jr. .I 200929 .U 90004753 .S Dis Colon Rectum 9001; 32(6):477-80 .M Follow-Up Studies; Human; Lymphatic Metastasis; Prognosis; Rectal Neoplasms/MO/*PA; Regression Analysis; Survival Rate. .T Prognostic value of direct spread in Dukes' C cases of rectal cancer. .P JOURNAL ARTICLE. .W Seventy-six cancers with involved lymph nodes but with limitation of direct spread in continuity to the bowel wall (Astler-Coller C1 cases) were matched with Astler-Coller C2 cases for clinical variables, macroscopic appearance of tumor, grade of differentiation, and number of positive lymph nodes. Despite this stringent matching, spread was shown to be an important prognostic variable in univariate survival analysis. Estimated five-year survival for Astler-Coller C1 cases was just below 80 percent, equivalent to B2 (Dukes' B) cases. When spread was analyzed in the presence of additional prognostic variables (character of invasive margin and lymphocytic infiltration) by multivariate modeling, its independent prognostic status was maintained. Improved survival for C1 cases was not explained by a lower incidence of local pelvic recurrence. Mechanisms to account for the better prognosis are proposed. This study reaffirms the importance of multivariate techniques of analysis in the assessment of prognosis of patients with rectal cancer. .A Jass JR; Love SB. .I 200930 .U 90004754 .S Dis Colon Rectum 9001; 32(6):481-7 .M Adult; Anus Neoplasms/*PA; Carcinoma, Squamous Cell/*PA; Condylomata Acuminata/*PA; Female; Human; Male; Middle Age; Neoplasms, Multiple Primary/*PA; Perineum/PA; Vulvar Neoplasms/PA. .T Malignant transformation of anorectal giant condyloma acuminatum (Buschke-Loewenstein tumor). .P JOURNAL ARTICLE. .W Giant condyloma acuminatum, originally described by Buschke and Loewenstein in 1925 as a lesion of the penis, is more rarely seen in the anorectum and is characterized by clinical malignancy in the face of histologic benignity; however, malignant transformation to frankly invasive squamous-cell carcinoma has been described. Malignant transformation has been reported in 15 patients with "ordinary" condylomata acuminata as well. Twenty giant condylomata acuminata have been previously reported, six of which (30 percent) went on to develop squamous-cell carcinoma. The authors report eight cases of giant condylomata acuminata with invasive squamous-cell carcinoma developing in four patients. Light and electron microscopic methods were used to verify the diagnosis of squamous-cell carcinoma and/or giant condyloma acuminatum in our cases. Human papillomavirus (HPV), known to cause condylomata acuminata, is also known to induce these tumors. The authors support the hypothesis that giant condyloma acuminatum represents an intermediate lesion in a pathologic continuum from condyloma acuminatum to squamous-cell carcinoma. These lesions have a propensity for recurrence, likelihood of malignant transformation, and significant mortality. Therefore, early and radical local excision, and in cases of recurrence, invasion, or malignant transformation, abdominoperineal resection, along with vigilant follow-up, provides the only current hope for cure. .A Creasman C; Haas PA; Fox TA Jr; Balazs M. .I 200931 .U 90004755 .S Dis Colon Rectum 9001; 32(6):488-91 .M Adenocarcinoma/CI/PA; Animal; Carcinogens; Colonic Neoplasms/CI/*PA; Dimethylhydrazines; Indomethacin/*PD; Kidney; Kidney Neoplasms/*PA; Male; Neoplasm Transplantation; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't. .T Effect of indomethacin in autotransplanted colonic tumors. .P JOURNAL ARTICLE. .W Seventy-five male Sprague-Dawley rats received weekly injections of dimethylhydrazine (DMH) for six months. Indomethacin was given orally to 40 of the rats. At the end of the allotted period, colonic tumors were autotransplanted into the subcapsular space of the left kidney. The autopsy demonstrated colonic tumors in 32 of 34 rats treated with DMH (94.1 percent), but only in 15 of 40 rats (37.5 percent) treated with DMH-indomethacin. Successful kidney autotransplantation was accomplished in 20 of 32 DMH-treated rats (63 percent) and in 5 of 15 DMH-indomethacin-treated rats (33.3 percent). Thus, the induction of colonic tumors by DMH and successful kidney autotransplants can be substantially abrogated by synchronous treatment with indomethacin. .A Rubio CA; Wallin B; Ware J; Sveander M; Duvander A. .I 200932 .U 90004756 .S Dis Colon Rectum 9001; 32(6):492-6 .M Adolescence; Adult; Aged; Crohn Disease/*CO; Follow-Up Studies; Human; Methods; Middle Age; Prognosis; Rectal Fistula/ET/PA/*SU; Recurrence; Reoperation; Retrospective Studies. .T Surgical management of anorectal fistulas in Crohn's disease. .P JOURNAL ARTICLE. .W A retrospective review of patients with Crohn's disease treated at our institution from 1973 to 1986 revealed 35 patients operated upon for anorectal fistulas. Twenty-nine had low intermuscular fistulas (multiple in seven), and six had high intermuscular (supralevator) fistulas. Fistulotomy alone was performed in 19 patients, and eight underwent partial fistulotomy and seton insertion. Five additional patients had proximal fecal diversion before fistulotomy. Three patients with severe colonic and anorectal disease underwent proctocolectomy as the initial procedure. Of the 32 patients who had fistulotomy performed, complete healing occurred in 30. Seven patients who healed required more than one operation for fistula. One patient was left with an asymptomatic fistula, and one required proctectomy for persistent symptomatic fistula and proctitis. Success of operation correlated with absence of rectal disease and quiescent disease elsewhere in the gastrointestinal tract. Aggressive medical treatment is required to control bowel disease preoperatively. In the majority of patients, subsequent surgery is justified and healing can be anticipated. .A Morrison JG; Gathright JB Jr; Ray JE; Ferrari BT; Hicks TC; Timmcke AE. .I 200933 .U 90004757 .S Dis Colon Rectum 9001; 32(6):497-9 .M Adult; Crohn Disease/*CO; Female; Human; Methods; Middle Age; Rectovaginal Fistula/ET/PA/*SU; Recurrence; Reoperation; Retrospective Studies. .T Results of operation for rectovaginal fistula in Crohn's disease. .P JOURNAL ARTICLE. .W A retrospective review of patients with Crohn's disease treated at our institution from 1973 to 1986 revealed 12 patients operated on for rectovaginal fistula. Disease involved the large intestine in 10 patients. Primary fistula repair was performed in four patients and four others had staged repair with preliminary fecal diversion. Four patients with severe colonic and anorectal disease had proctocolectomy performed as the first procedure. Of eight patients who underwent fistula repair, complete healing occurred in six. One patient has a persistent fistula, which is minimally symptomatic, and the other required proctocolectomy after three unsuccessful repairs. Success of operation correlated with quiescent intestinal disease and absence of rectal involvement. In selected patients with symptomatic fistulas, surgical repair is indicated and healing can be anticipated. .A Morrison JG; Gathright JB Jr; Ray JE; Ferrari BT; Hicks TC; Timmcke AE. .I 200934 .U 90004758 .S Dis Colon Rectum 9001; 32(6):500-4 .M Adolescence; Adult; Aged; Aged, 80 and over; Body Weight; Colostomy/*AE; Emergencies; Follow-Up Studies; Human; Ileostomy/*AE; Middle Age; Reoperation; Retrospective Studies; Risk Factors. .T Some factors influencing the outcome of stoma surgery. .P JOURNAL ARTICLE. .W In a retrospective study, the procedure and follow-up of 266 patients with 345 stomas on the small and large bowel were reviewed to reveal possible etiologic factors for stomal complications. The overall complication rate for creating a stoma was 36 percent. No differences in overall complication rate were encountered when comparing acute and elective management; however, high output stomas and necrosis were encountered more often in the acutely managed group. Preoperative contamination was followed more often by stomal retraction. Septic events, however, occurred less frequently than in the noncontaminated procedures. Adequate supply with antibiotics might account for the lack of difference in these complications between the two groups. Antibiotics might not have prevented low-grade infections giving rise to retractive reaction. The influence of body weight was evaluated by the Quetelait index. It was demonstrated that moderate obesity had no significant influence on the outcome of the procedure. Adipose patients had a statistically significant larger number of necroses. This may be due to the relatively short and fatty mesenterium causing a compromised circulation. The outcome of stoma surgery was greatly influenced by bowel quality. Crohn's disease and bowel ischemia were encountered in 50 percent of stoma complications. In ischemic disease, significantly more necrosis was found. Retraction of the stoma occurred more often in Crohn's disease. Chronic ulcerative colitis did not have a higher complication rate. .A Leenen LP; Kuypers JH. .I 200935 .U 90004762 .S Dis Colon Rectum 9001; 32(6):521-3 .M Acquired Immunodeficiency Syndrome/*CO; Adult; Anus Neoplasms/*ET/PA; Case Report; Human; Lymphoma, Non-Hodgkin's/*ET/PA; Male. .T Perianal lymphoma as a manifestation of the acquired immune deficiency syndrome. Report of a case. .P JOURNAL ARTICLE. .W A case of nonHodgkin's lymphoma of the perianal region in a patient with AIDS is reported. The unusual features of AIDS-related lymphoma and the possible role of immunodeficiency increasing susceptibility to oncogenic viruses are discussed. .A Morrison JG; Scharfenberg JC; Timmcke AE. .I 200936 .U 90004763 .S Dis Colon Rectum 9001; 32(6):524-7 .M Adolescence; Case Report; Colon/*BS/PA; Colonoscopy; Female; Gastrointestinal Hemorrhage/ET; Human; Varicose Veins/*/CO/DI/PA. .T Colonic varices. Report of a case. .P JOURNAL ARTICLE. .W A 14-year-old girl who had colonic bleeding caused by colonic varices is described. Upper gastrointestinal endoscopy, radiography of the small and large bowel, and vascular studies of the superior and inferior mesenteric arteries and the portal vein were all reported to be normal. Submucosal varices, however, were identified colonoscopically in relation to the hepatic flexure and the sigmoid colon. Dilatation of subserosal right colonic vascular channels was identified at operation. Right hemicolectomy was performed and there has been no further bleeding. No obvious mesenteric arteriovenous communications were identified histologically. .A Isbister WH; Pease CW; Delahunt B. .I 200937 .U 90004764 .S Dis Colon Rectum 9001; 32(6):528-32 .M Aged; Aged, 80 and over; Anastomosis, Surgical/MT; Case Report; Female; Human; Intestinal Obstruction/*SU; Irrigation/IS/MT; Methods; Middle Age; Sigmoid/SU; Sigmoid Diseases/*SU; Suction/IS. .T Complete obstruction of the sigmoid colon treated by primary resection and anastomosis--an improved technique (preliminary report). Report of three cases. .P JOURNAL ARTICLE. .W Three patients with complete colonic obstruction treated by primary resection and anastomosis with intraoperative colon tube decompression and bowel lumen sterilization without a protective colostomy are presented. An improved colonic decompressor was used. It is postulated that this procedure is an alternative safe technique in patients with colonic obstruction in whom an end-colostomy, mucous fistula, or Hartmann pouch would be necessary. .A Hardy TG Jr; Aguilar PS; Stewart WR. .I 200938 .U 90004765 .S Dis Colon Rectum 9001; 32(6):534-5 .M Colostomy/*IS; Human; Prolapse; Recurrence. .T A simple device for prolapsing loop colostomies. .P JOURNAL ARTICLE. .W A simple device, applied to a conventional stomal appliance, prevents loop colostomy prolapse. .A Fucini C. .I 200939 .U 90004766 .S Dis Colon Rectum 9001; 32(6):536-7 .M Antineoplastic Agents/AD; Catheterization/*MT; Human; Infusions, Intravenous/MT; Portal Vein/*. .T Simple and safe method for operative cannulation of the portal vein. .P JOURNAL ARTICLE. .W A method of portal vein cannulation via the omental vasculator is described. This mode of vascular access, which requires only five or ten minutes of additional operating time, can be used for adjuvant or therapeutic portal vein infusion of chemotherapy. .A Umemoto S; Amemiya T; Koizumi K. .I 200940 .U 90004767 .S Dis Colon Rectum 9001; 32(6):538-9 .M Human; Intestines/*SU; Surgical Staplers/*AE; Sutures/*AE. .T Pursestring complication using the Auto Suture Company PREMIUM CEEA stapling device. .P JOURNAL ARTICLE. .W Detachment of the anvil when using the Auto Suture Company PREMIUM CEEATM stapling device is described. This may be avoided by not double-looping the pursestring around the bowel and by not tying the pursestring too tightly. .A Fozard JB; Lee PW. .I 200941 .U 90004768 .S Dis Colon Rectum 9001; 32(6):545 .M Acute Disease; Dilatation/*AE; Fissure in Ano/*TH; Human. .T Complications of anal dilatation for acute anal fissure [letter] .P LETTER. .A Gutman H; Gonen P; Deutsch AA. .I 200942 .U 90004769 .S Dis Colon Rectum 9001; 32(6):545 .M Diet/AE; Fissure in Ano/*ET; Human; Risk Factors. .T Fissure-in-ano risk factors [letter; comment] .P COMMENT; LETTER. .A Weaver PA. .I 200943 .U 90004770 .S Dis Colon Rectum 9001; 32(6):545-6 .M Female; Human; Intestinal Neoplasms/*PA; Intestine, Large; Male. .T Site distribution of carcinoma of the large intestine [letter; comment] .P COMMENT; LETTER. .A Fogler R. .I 200944 .U 90004771 .S Dig Dis Sci 9001; 34(10):1489-93 .M Animal; Animal Nutrition; Atropine/PD; Dogs; Feeding Behavior/PH; Satiation/DE/*PH; Stomach/*PH; Support, U.S. Gov't, P.H.S.. .T Gastric distension is a physiologic satiety signal in the dog. .P JOURNAL ARTICLE. .W Gastric distension is thought to produce satiety, but whether this effect is seen during physiologic distension by food is unknown. The purpose of this study was to determine whether levels of gastric distension seen during a meal have a satiety effect and whether the nutrient value of the meal was important. Four dogs were prepared with gastric, duodenal, and esophageal fistulas. Physiologic distension was determined by allowing the animals to eat liquid nutrient diet until sated and measuring the volume consumed and the time it took to consume it (means 2000 ml in 4 min). To test the effect of gastric distension on satiety, distension was produced during sham feeding by infusions of either liquid nutrient, inert liquid (Karaya), or by a water-filled balloon. Lower degrees of distension were also tested to determine if a dose-response relationship existed. Balloon, inert, and nutrient distension all inhibited sham feeding dose-dependently. Peak inhibitions of sham feeding caused by physiologic gastric distension (balloon, inert, nutrient) were 69 +/- 5%, 67 +/- 12%, and 61 +/- 6%, respectively. In all cases, maximal distension terminated sham feeding before the end of the feeding period. The effect of gastric distension on feeding was not blocked by pretreatment with atropine (50 micrograms/kg). Thus, graded degrees of gastric distension, comparable to those seen during ingestion of a normal meal, produced graded inhibition of food intake by a noncholinergic mechanism and independent of the nutrient properties of the food. .A Pappas TN; Melendez RL; Debas HT. .I 200945 .U 90004772 .S Dig Dis Sci 9001; 34(10):1494-500 .M Cimetidine/*AD; Double-Blind Method; Drug Administration Schedule; Duodenal Ulcer/*DT; Eating/*; Endoscopy; Gastric Juice/*SE; Human; Patient Compliance; Support, Non-U.S. Gov't. .T Reducing meal-stimulated acid secretion versus reducing nocturnal acid secretion for healing of duodenal ulcer. .P JOURNAL ARTICLE. .W Both meal-stimulated and nocturnal acid secretions have been shown to be abnormally increased in patients with duodenal ulcer. The relative efficacy of an acid-reducing regimen aimed specifically at controlling postprandial acid secretion compared with one that controls nocturnal acid secretion is, however, not known. The endoscopic healing rates at weeks 2, 4, 6, 8, 10, and 12 of three cimetidine regimens with identical total daily dose--bedtime (1200 mg), mealtime (400 mg three times a day with meals), and reference (200 mg three times a day with meals and 600 mg at bedtime)--were compared in a randomized study on 141 patients with endoscopically proven duodenal ulcer. Evaluating endoscopists were blinded to patients' form and duration of treatment and their clinical progress; patients were unaware of the comparative design of the study. Life-table analysis for the 12 weeks of observation revealed that the mealtime regimen resulted in significantly (P less than 0.05) better healing rates than either the bedtime or the reference regimen. The differences were accounted for largely by the significantly (P less than 0.04) better healing rate at two weeks with the mealtime regimen (68%) than with either the bedtime (47%) or the reference (45%) regimen. These findings indicate that a regimen that aims at controlling meal-stimulated acid secretion achieves a faster healing rate than one that aims at controlling nocturnal acid secretion in the treatment of duodenal ulcer, and they suggest that postprandial acid secretion plays a greater role than nocturnal acid secretion in the pathophysiology of this condition. .A Lam SK; Hui WM; Ng MM; Lok AS; Lai CL; Branicki F; Lau WY; Poon GP. .I 200946 .U 90004773 .S Dig Dis Sci 9001; 34(10):1501-4 .M Adolescence; Biopsy; Campylobacter Infections/*EP; Child; Duodenitis/DI/EP/*MI/PA; Endoscopy; Gastric Mucosa/MI; Gastritis/DI/EP/*MI/PA; Human; Prospective Studies. .T Campylobacter pylori-related gastrointestinal disease in children. Incidence and clinical findings. .P JOURNAL ARTICLE. .W Over a one-year period, 95 children and adolescents presenting with epigastric pain and/or vomiting, and without associated risk factors for development of peptide disease, underwent endoscopic antral biopsies for pathologic diagnosis and to detect presence of Campylobacter ss. pylori (C. pylori). Additional biopsies of the esophagus, stomach, and duodenum were obtained for histologic evaluation. C. pylori was identified in 16 patients (16.8%), all of whom had evidence of acute and/or chronic gastritis. Significant discriminating factors between C. pylori-positive and -negative subjects included age at presentation (positive vs negative = 14.6 vs 9.9 years, P less than 0.01), biopsy-confirmed gastritis (100% vs 30.4%, P less than 0.001), and diagnosis of duodenitis alone (0% vs 46.8%, P less than 0.001). Risk for bacterial colonization was significantly higher in the presence of endoscopic gastritis (P less than 0.001). Among C. pylori-positive patients, none responded to standard antiulcer therapy (H2-receptor antagonists, antacids). Symptomatic and histologic remission was achieved utilizing combined therapy with bismuth subsalicylate and antibiotics. Seven of 79 C. pylori-negative patients with biopsy-proven gastritis who responded poorly to antisecretory therapy had the organism identified in follow-up antral biopsies; these patients improved clinically following treatment for C. pylori. These data suggest that C. pylori is a significant factor in the etiology of upper gastrointestinal tract inflammatory disease in pediatrics, and presence of the organism should be evaluated, particularly in children with evidence of acute and/or chronic gastritis. .A Glassman MS; Schwarz SM; Medow MS; Beneck D; Halata M; Berezin S; Newman LJ. .I 200947 .U 90004774 .S Dig Dis Sci 9001; 34(10):1505-10 .M Colectomy/AE; Colitis, Ulcerative/SU; Endoscopy; Human; Ileitis/DT/*ET/PA; Ileostomy/*AE. .T Pouch ileitis. .P JOURNAL ARTICLE. .W Pouch ileitis is the most poorly understood complication of ileal reservoir surgery. Variability in definition of this syndrome may account for differences in incidence rate, associated symptoms, and response rate to therapy present in the literature. Outcomes of 19 episodes of pouch ileitis in patients having undergone prior colectomy and continent ileostomy construction for presumed ulcerative colitis were analyzed. An episode of pouch ileitis was characterized by: (1) abdominal pain, (2) increased ileal output, (3) mucosal inflammation within the continent ileostomy, and (4) absence of other recognized concurrent postoperative complications. The mean time of occurrence after construction of the continent ileostomy was 25 months (range 3-54 months). The mean length of follow-up of patients included in this analysis was 49 months from the time of continent ileostomy construction (range 22-101 months). Associated clinical symptoms included bloody effluent (53%), nausea or emesis (47%), and fever (42%). Endoscopic features were often nonspecific, with mucosal erythema (84%), edema (79%), friability (58%), and mucosal ulceration (53%) the most common. In those episodes of pouch ileitis where ileoscopy revealed no evidence of mucosal ulceration, complete resolution of the episode occurred 89% of the time, with 78% treated with antibiotics alone. In those episodes where mucosal ulceration was described on ileoscopy, 40% of episodes completely resolved after medical treatment, 20% with antibiotics alone. The varied clinical symptoms, endoscopic findings, and response to treatment raises the possibility that what has previously been described in the literature as pouch ileitis may be a heterogeneous group not of single etiology.(ABSTRACT TRUNCATED AT 250 WORDS) .A Zuccaro G Jr; Fazio VW; Church JM; Lavery IC; Ruderman WB; Farmer RG. .I 200948 .U 90004775 .S Dig Dis Sci 9001; 34(10):1511-5 .M Adult; Cecum/PH; Female; Gastrointestinal Hormones/*SE; Gastrointestinal Motility/*DE; Human; Imidazoles/*PD; Intestine, Small/PH; Male; Peptides/BL; Receptors, Serotonin/*DE; Secretory Rate/DE; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Effect of selective 5HT3 antagonist (GR 38032F) on small intestinal transit and release of gastrointestinal peptides. .P JOURNAL ARTICLE. .W Antagonists of 5-hydroxytryptamine type 3 (5HT3) receptors reduce the nausea induced by cisplatinum, but the effects of these agents on 5HT3 receptors in the human gut remain to be defined. We examined the actions of one of these drugs (Glaxo GR 38032F) on small intestinal transit and mouth-to-cecum transit times in healthy man. We also quantified its effects on the release of peptide YY (PYY), neurotensin, human pancreatic polypeptide, gastrin-cholecystokinin, and motilin. Ten healthy volunteers were enrolled in a randomized, double-blind, placebo-controlled crossover study. Following a single intravenous dose of GR 38032F (0.15 mg/kg), we measured the time to appearance in plasma of sulfapyridine after injection of salicylazosulfapyridine into the duodenum. This was used as a measure of duodenocecal transit. The appearance of hydrogen in breath after ingestion of a meal containing lactulose was also correspondingly used to quantify the mouth-to-cecum transit of the "head" of the meal. Gastrointestinal hormones were assayed in plasma by specific RIAs; samples were drawn fasting (10 min after injection) and after breakfast (358 calories: 15.7 g protein, 55.4 g carbohydrate, 8.1 g fat). The postprandial integrated response and peak release of PYY was decreased by GR 38032F. There was also a trend for the peak release of neurotensin to be reduced. GR 38032F did not significantly alter small intestinal transit times or mouth-to-cecum transit times. We conclude that GR 38032F does not have a major effect on small intestinal transit in health. .A Talley NJ; Phillips SF; Haddad A; Miller LJ; Twomey C; Zinsmeister AR; Ciociola A. .I 200949 .U 90004776 .S Dig Dis Sci 9001; 34(10):1516-20 .M Animal; Dogs; Fasting; Fatty Acids/*PD; Female; Gastrointestinal Motility/*DE; Ileum/*PH/RI; Jejunum/PH/RI; Muscle Contraction; Muscle, Smooth; Structure-Activity Relationship; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Stimulation of ileal emptying by short-chain fatty acids. .P JOURNAL ARTICLE. .W We have shown previously that short-chain fatty acids (mixtures of acetic, propionic, and butyric acids; SCFAs) in the proportions found usually in stool water stimulate fasting ileal motility. Based on indirect evidence, we proposed that these motor patterns (bursts of phasic pressure waves that were propagated) would be propulsive, but the capacity of these stimulated patterns of motility to propel contents has not been established directly. Healthy, surviving dogs were provided with motility sensors and a cannula through which SCFAs could be instilled into the ileum. Boluses of SCFAs were much more likely to stimulate phasic bursts of motility than was saline. Scintigraphic studies using a gamma camera showed that the motility stimulated by SCFAs was propulsive and that the ileum was thereby emptied. We also tested whether SCFAs were equally effective stimuli during fasting and after food. SCFAs were equally effective during fasting and soon after food, but in the late postprandial period, when the meal reached the ileum, SCFAs were much less likely to stimulate motility. These observations shed further light on the capacity of the ileum to sense and react to the nature of the contents. .A Fich A; Phillips SF; Hakim NS; Brown ML; Zinsmeister AR. .I 200950 .U 90004777 .S Dig Dis Sci 9001; 34(10):1521-7 .M Animal; Dogs; Dose-Response Relationship, Drug; Female; Gastrointestinal Motility/*DE; Ileum/*PH; Muscle Contraction/DE; Neurotensin/AD/*PD; Support, Non-U.S. Gov't; Video Recording. .T Neurotensin changes the motor pattern in canine ileum from propulsive to segmenting. .P JOURNAL ARTICLE. .W Modulation of ileal propulsive motility by different doses of neurotensin has been determined in detail. In conscious dogs neurotensin (2.5, 5, and 10 pmol/kg/min) was intravenously infused during the propulsive motor pattern induced by an acaloric viscous meal. Motor patterns were recorded by seven closely spaced strain gauge transducers and analyzed by a computerized method. Luminal transit was measured fluoroscopically. Neurotensin changed the propulsive motor pattern induced by the acaloric meal into a segmenting pattern. Effects were dose-dependent and most striking at a dose of 10 pmol/kg/min. The transit of luminal contents decreased from 20 to 8 cm/min. This was achieved by the increase in the number of stationary contractions (31 vs 55%), the reduction in the length of contraction spread (3.8 vs 1.8 cm), and the decrease in the number of contractions (11.5 vs 9.2 contractions/min). The contraction force was enhanced from 67 to 107 mN. Because of the marked effects on ileal motor patterns, neurotensin might be involved in the regulation of digestive motility in the distal small intestine. .A Siegle ML; Ehrlein HJ. .I 200951 .U 90004778 .S Dig Dis Sci 9001; 34(10):1528-35 .M Adult; Colitis, Ulcerative/*BL/DI/PP; Crohn Disease/*BL/DI/PP; Female; Follow-Up Studies; Human; Immunoassay; Male; Sex Factors; Support, U.S. Gov't, P.H.S.; Vasoactive Intestinal Peptide/*BL. .T Vasoactive intestinal peptide as a laboratory supplement to clinical activity index in inflammatory bowel disease. .P JOURNAL ARTICLE. .W Circulating levels of vasoactive intestinal peptide (VIP) in plasma were measured in gauging activity in inflammatory bowel disease (IBD). One hundred-fifteen adult IBD patients were studied cross-sectionally and prospectively, 48 with ulcerative colitis (UC) and 67 with Crohn's disease (CD). Sequential samples of plasma were assayed for VIP by specific radioimmunoassay. Sixty males and 55 females, ranging in age from 22 to 76 years were studied over six months. The results revealed a strong, positive association between VIP levels and clinical activity, both at baseline (r = 0.38, P less than 0.001) and follow-up (r = .41, P less than 0.001). The ability of the VIP immunoassay to gauge clinical activity was also evaluated where VIP concentrations above 30 pg/ml were defined as abnormal. At baseline, sensitivity (specificity) was found to be 81% (55%). The predictive value of a positive (negative) test was 57% (80%). These estimates did not differ at follow-up. Examination of paired plasma samples from intermittently active patients revealed nearly twofold increases (P less than 0.05) in VIP concentration during active periods of disease. The data suggest that plasma VIP levels may be a valuable laboratory parameter in gauging activity in inflammatory bowel disease. .A Duffy LC; Zielezny MA; Riepenhoff-Talty M; Byers TE; Marshall J; Weiser MM; Graham S; Ogra PL. .I 200952 .U 90004779 .S Dig Dis Sci 9001; 34(10):1536-41 .M Age Factors; Carcinoma/EP/*ET; Colitis, Ulcerative/*CO/PA; Colonic Neoplasms/EP/*ET; Colonoscopy; Female; Human; Intestinal Mucosa/PA; Male; Prospective Studies; Risk Factors; Support, Non-U.S. Gov't; Survival Analysis; Time Factors. .T Hazard rates for dysplasia and cancer in ulcerative colitis. Results from a surveillance program. .P JOURNAL ARTICLE. .W The risk of colon cancer in patients with ulcerative colitis is related to the duration and extent of disease. Prior reports have suggested that patients with onset of disease in childhood have a high risk of cancer. These risk factors were analyzed in 99 patients in a surveillance program of annual colonoscopy to detect mucosal dysplasia. All patients had pancolitis for at least eight years. The mean age at symptom onset was 23.2 years and the mean duration of disease at entry was 17 years. An average of 4.2 tests/patient were performed, and 91% were completely followed through 1985. Cancer risk was expressed as the hazard rate or the annual probability that a patient free of cancer would develop cancer after survival to a given time period. The hazard rate for high-grade dysplasia or cancer in patients with pancolitis measured from symptom onset was 2.5% at 20 years, 4% at 25 years, 7% at 30 years, 13% at 35 years, and 20% at 40 years. Sex was not a significant predictor of cancer, but older age at symptom onset was a predictor of dysplasia and cancer. From these data, the annual hazard rate of developing high-grade dysplasia or cancer can be estimated in patients with pancolitis based on an individual's age at symptom onset and duration of disease. .A Lashner BA; Silverstein MD; Hanauer SB. .I 200953 .U 90004781 .S Dig Dis Sci 9001; 34(10):1547-52 .M Ascites/MI; Bacterial Infections/*IM; Complement/*PH; Human; Immunity, Cellular/*; Immunoglobulins/*PH; Leukocyte Count; Liver Cirrhosis/*CO/IM; Peritonitis/*IM; Prospective Studies; Support, U.S. Gov't, P.H.S.; T-Lymphocytes/IM. .T Role of serum complement, immunoglobulins, and cell-mediated immune system in the pathogenesis of spontaneous bacterial peritonitis (SBP). .P JOURNAL ARTICLE. .W Spontaneous bacterial peritonitis (SBP) is a common complication of advanced liver disease, which has a reported prevalence of between 4 and 27%. Frequent bacteremias due to inadequate host defense mechanisms, particularly the reticuloendothelial system (RES), with seeding of an ascitic fluid that lacks a normal opsonic activity, is believed to be the principal cause of SBP. Little data exist as to the role of serum levels of complement and immunoglobulins as well as the cell-mediated immune system in the pathogenesis of SBP. The aim of this study was to determine the serum levels of the third and fourth components of complement (C3, C4), total hemolytic complement activity (CH100), and properdin factor B (PFB) and immunoglobulins G, A, and M and various T-cell parameters in individuals admitted to hospital with ascites and advanced liver disease and to determine whether one or more of these factors could be used to predict the development of SBP in patients with advanced liver disease. Fourteen consecutive patients (nine male and five female; age 47.5 +/- 3.1 years, mean +/- SEM) with end-stage liver disease and ascites, who were evaluated for possible liver transplant at the University of Pittsburgh and who developed SBP, comprised the study group. The diagnosis of SBP was determined by positive ascitic fluid culture (three patients) and/or ascitic fluid neutrophil count of greater than 250 cells/mm3 (all patients). The control group consisted of 14 patients, matched for type of liver disease, age, and sex, who did not develop SBP.(ABSTRACT TRUNCATED AT 250 WORDS) .A Rabinovitz M; Gavaler JS; Kumar S; Kajani M; Van Thiel DH. .I 200954 .U 90004782 .S Dig Dis Sci 9001; 34(10):1553-8 .M Adult; Aged; Biopsy, Needle/*MT; Human; Liver Diseases/*DI; Memory/DE; Midazolam/PD/*TU; Middle Age; Patient Compliance; Questionnaires; Support, U.S. Gov't, P.H.S.. .T Use of midazolam for percutaneous liver biopsy. .P JOURNAL ARTICLE. .W The standard procedure for percutaneous liver biopsy (PLB) involves only the use of local anesthesia. However, at times, a PLB can be frightening and uncomfortable. Such experiences often limit the willingness of patients to undergo subsequent follow-up biopsies. To investigate the ability of midazolam, a new water-soluble benzodiazepine preparation, noted for its potency, rapid onset of action, and amnestic qualities, to enhance patient acceptability of a follow-up liver biopsy, a "sedative dose" of midazolam (2 mg) or saline was administered immediately prior to and following a percutaneous liver biopsy. The initial dose was used to sedate the subject while not impairing patient cooperation during the biopsy procedure; the second dose was used to induce amnesia for the biopsy procedure. The next morning patient recollection for the preceding biopsy procedure and their willingness to undergo a future PLB were assessed using a questionnaire. Forty-one patients (ages 18-78) were randomized to receive either midazolam (N = 21) or saline/placebo N = 20) treatment. All PLBs were obtained with a Trucut needle. All subjects were given 2-5 cc of 2% xylocaine local anesthetic at the biopsy site. The questionnaire utilized evaluated patient experience of the procedure with respect to their recall, level of anxiety during the procedure, and willingness to undergo a repeat procedure. The data obtained revealed that those receiving midazolam admitted to experiencing less discomfort during the biopsy procedure (P less than 0.04) and had less memory for the procedure (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) .A Brouillette DE; Yoo YK; Chien MC; Rabinovitz M; Tarter RE; Van Thiel DH. .I 200955 .U 90004785 .S Dig Dis Sci 9001; 34(10):1571-5 .M Hepatectomy; Hepatoma/CO/PA/*SU; Human; Liver Cirrhosis/CO/PA/*SU; Liver Neoplasms/CO/PA/*SU; Liver Transplantation; Survival Rate. .T Reappraisal of surgical treatment of small hepatocellular carcinomas in cirrhosis: clinicopathological study of resection or transplantation. .P JOURNAL ARTICLE. .W Thirty-two patients with hepatocellular carcinoma (HCC) occurring in individuals with cirrhosis had a potentially curative surgical procedure. Twenty-two had segmental hepatic resections (HR), and 10 underwent orthotopic liver transplantation (OLTx). The diagnosis of hepatic malignancy was established in each case preoperatively, and each case was studied intraoperatively by means of sonography. Postoperatively each surgical specimen was examined pathologically with attention to the possibility of intrahepatic tumor spread. Twenty-three of the 32 patients had single small HCC lesion (less than 5 cm diameter) identified preoperatively. Sixteen of these underwent HR and seven underwent OLTx. Multiple additional neoplastic lesions were found in 19% of the 16 HR cases and in 14% of those undergoing OLTx when the resection specimens were examined pathologically. Vascular invasion was present in 43% of the OLTx patients and in 25% of the HR patients. Subtotal hepatic resection for small HCC occurring in cirrhosis has produced few long-term survivals. Both pre- and intraoperative sonography have been shown to underestimate the extent and distribution of these tumors. Based upon this experience that (1) vascular spread occurs often in HCC and (2) a high risk of postoperative hepatic failure can be expected after HR in cirrhotic individuals, OLTx is the most rational surgical procedure for such cases as it has the potential to cure. .A Belli L; Romani F; Belli LS; De Carlis L; Rondinara G; Baticci F; Del Favero E; Minola E; Donato F; Mazzaferro V; et al. .I 200956 .U 90004786 .S Dig Dis Sci 9001; 34(10):1576-80 .M Aged; Alanine Aminotransferase/BL; Amoxicillin/*AE; Antibiotics, Combined/AE; Bilirubin/BL; Biopsy; Child, Preschool; Cholestasis, Intrahepatic/*CI/PA; Clavulanic Acids/*AE; Hepatitis, Toxic/*ET/PA; Human; Male; Middle Age; Time Factors. .T Cholestatic hepatitis due to antibacterial combination of amoxicillin and clavulanic acid (augmentin) [see comments] .P JOURNAL ARTICLE. .W Five case histories are presented of patients developing cholestatic hepatitis associated with the intake of the antibiotic combination agent amoxicillin and clavulanic acid (Augmentin). In two of these cases, signs of hepatic injury recurred after readministration of this combination but not after the intake of amoxicillin alone. In none of the patients was another cause for cholestatic hepatitis found and extrahepatic causes were excluded by ultrasonography, CT scanning, or ERCP. Most viral causes of hepatic injury were excluded in these patients. With the exception of one patient, who developed a transient rash, no immunoallergic signs were present. Biopsy in two patients showed extensive cholestasis without significant necrosis. Clavulanic acid seems to be responsible for this adverse effect. .A Stricker BH; Van den Broek JW; Keuning J; Eberhardt W; Houben HG; Johnson M; Blok AP. .I 200957 .U 90004787 .S Dig Dis Sci 9001; 34(10):1581-4 .M Acute Disease; Animal; Catalase/TU; Dogs; Free Radicals; Heart Diseases/*ET/PP; Hemodynamics; Hemorrhage; Lung Diseases/*ET/PP; Oxygen/*PH; Pancreatitis/CO/*PP; Superoxide Dismutase/TU; Vascular Resistance. .T Role of reactive oxygen metabolites in early cardiopulmonary changes of acute hemorrhagic pancreatitis. .P JOURNAL ARTICLE. .W The role of reactive oxygen metabolites in extrapancreatic organ dysfunction associated with acute hemorrhagic pancreatitis was studied in dogs. Experimental pancreatitis was induced by the intraductal infusion of activated trypsin and taurocholate. Cardiac output, pulmonary and systemic blood pressure, pulmonary wedge pressure, central venous pressure, heart rate, blood gases and serum amylase were measured. Cardiac index, pulmonary and systemic vascular resistance, and the right and left stroke work were calculated. Systemic arterial and venous blood pressure and cardiac index gradually declined over 6 hr, while pulmonary mean blood pressure and pulmonary vascular resistance increased. Pretreatment of pancreatitis with catalase and superoxide dismutase prevented the rise in mean pulmonary blood pressure, moderated the rise in pulmonary vascular resistance, and decreased the rate and extent of the fall in cardiac index. These data suggest that reactive oxygen metabolites may play some role in the extraabdominal organ manifestations of acute pancreatitis. .A Chardavoyne R; Asher A; Bank S; Stein TA; Wise L. .I 200958 .U 90004788 .S Dig Dis Sci 9001; 34(10):1585-9 .M Beds/*; Gastroesophageal Reflux/*ET; Human; Hydrogen-Ion Concentration; Posture; Prospective Studies. .T Does sleeping on a waterbed promote gastroesophageal reflux? .P JOURNAL ARTICLE. .W We conducted a randomized prospective study with extended intraesophageal pH monitoring on two consecutive nights to test the hypothesis that a waterbed (WB) might increase recumbent acid exposure compared to a regular bed (RB). We studied 10 controls (mean age 29 years; five males, five females) with no history of reflux symptoms more than two times per month. We also studied 10 reflux patients (mean age 42 years; seven males, three females) with symptoms at least five days a week and documented recumbent reflux, with or without upright reflux, by previous 24 hr pH study. A standard meal (56% fat) was provided at 6 PM. After randomization, the subjects and patients slept on the assigned bed (WB or RB) in one nearby hotel. The pH probe was removed the next morning at 8 AM. On the same day, the pH probe was inserted at 4 PM and the routine was repeated with use of the other bed. No significant difference (P greater than 0.05; paired t test) was found between the regular bed and waterbed in any measurement of recumbent reflux. Our study does not support the hypothesis that greater recumbent reflux may occur when sleeping flat on a waterbed compared to a regular bed. It does not, however, absolutely refute the possible association of waterbed use with esophagitis, since elevation of the head of a waterbed is not possible. .A Wang JC; Castell DO; Sinclair JW; Wu WC. .I 200959 .U 90004789 .S Dig Dis Sci 9001; 34(10):1590-9 .M Adult; Biomechanics; Deglutition/*PH; Esophagogastric Junction/PH; Esophagus/*PH; Female; Human; Hydrostatic Pressure; Male; Manometry; Middle Age; Peristalsis; Pharynx/*PH; Support, Non-U.S. Gov't; Water. .T Normal pharyngoesophageal motility. A study of 50 healthy subjects. .P JOURNAL ARTICLE. .W Upper esophageal manometry is technically problematic. Published normal values are, therefore, few and wide ranging, reflecting catheter and recording-system variables, while the reproducibility of measurements and the influence of food consistency have been little studied. In this investigation, 50 healthy volunteers were studied with (1) a 2.8-mm-diameter six-sensor catheter-mounted transducer assembly and (2) a 3.2 X 7.2-mm sleeve device linked to a computerized recorder with a pressure-sample rate of 32/sec. The study protocol included water, bread, and semisolid swallows. Upper esophageal sphincter (UES) tonic pressures measured with the catheter-mounted assembly were lower and more reproducible than pressures measured with the sleeve system. Compared with water, bread swallows showed greater pharyngeal and sphincter after-contraction pressures, while semisolid swallows had less complete sphincter relaxation. Duration of pharyngoesophageal contractions was greater with bread or semisolid than water. The observations have established normal values for measurements of UES function and, in addition, have shown that (1) catheter variables significantly influence the measurement of upper sphincter tonic pressure, (2) pressures recorded with the catheter-mounted transducer are most reproducible, and (3) pharyngoesophageal motility patterns vary significantly according to the substance swallowed. .A Wilson JA; Pryde A; Cecilia A; Macintyre CC; Heading RC. .I 200960 .U 90004790 .S Dig Dis Sci 9001; 34(10):1600-5 .M Administration, Oral; Atropine/AD/PD; Catheterization; Drug Administration Schedule; Esophagogastric Junction/*DE; Esophagus/*DE; Gastrointestinal Motility; Human; Injections, Intravenous; Manometry; Peristalsis/*DE; Piperidines/AD/AE/*PD. .T Effects of cisapride on distal esophageal motility in humans. .P JOURNAL ARTICLE. .W Peristaltic contractions of the distal esophageal body and lower esophageal sphincter tone were evaluated in patients affected by gastroesophageal reflux disease after either acute intravenous (8.0 mg) administration or two oral doses (5.0 mg and 10.0 mg) of cisapride and in healthy controls after a 10.0-mg oral dose of cisapride. Intravenous cisapride administration enhanced the amplitude and duration of primary peristalsis and the lower esophageal sphincter tone, which reached normal control values. Likewise, the 10.0-mg oral dose effectively enhanced the lower esophageal sphincter resting pressure in both controls and in reflux patients, whereas the amplitude and duration of primary peristalsis was improved only in controls. The 5.0-mg oral dose of cisapride proved ineffective on distal esophageal motor activity in reflux patients. To evaluate whether atropine is capable of modifying the effects of cisapride on distal esophageal motor activity, cisapride was administered intravenously before and during intravenous atropine administration. Effects of cisapride on peristaltic contractions were completely blocked by atropine, irrespective of whether atropine was administered before or after cisapride. The lower esophageal sphincter pressure response to cisapride varied according to the sequence of drug administration, showing no effect when cisapride followed atropine administration and, when this sequence was reversed, no significant atropine-induced inhibition on cisapride-stimulated lower esophageal sphincter pressure. It is suggested that cisapride enhances distal esophageal motor activity by means of a muscarinic receptor mechanism at the level of the distal esophageal body and, at least in part, via a muscarinic-independent mechanism at the level of the lower esophageal sphincter. .A Corazziari E; Bontempo I; Anzini F. .I 200961 .U 90004791 .S Dig Dis Sci 9001; 34(10):1606-10 .M Abdomen; Adult; Esophagogastric Junction/*PH; Female; Human; Hydrostatic Pressure; Male; Manometry/MT; Middle Age; Posture; Reflex; Stomach/PH. .T Response of lower esophageal sphincter to alterations of intraabdominal pressure. .P JOURNAL ARTICLE. .W It is well documented that lower esophageal sphincter pressure increases significantly in response to increases in intraabdominal pressure in order to maintain the gastroesophageal barrier. The mechanism by which this response is elicited is controversial. It has been suggested that the response of the sphincter persists after the intraabdominal pressure stimulus is removed. The present study sought to define the response of the sphincter to increased intraabdominal pressure (achieved by straight leg raising) by continuously monitoring it with the Dent sleeve in a group of 10 normal volunteers. A reproducible pressure profile was observed in both the sphincter and the stomach, characterized by an initial peak, a sustained plateau, and a second peak. The pressure profiles of the stomach and the sphincter were closely approximated and peak and plateau pressures for both did not differ significantly. The onset and offset of the pressure increase were simultaneous in the stomach and the sphincter. No significant changes in sphincter pressure were noted when the rapid pull-through technique was used. This study defines the pressure profiles of the stomach and the lower esophageal sphincter zone during increased intraabdominal pressure in man. Our data suggest that the response of the sphincter is passively mediated. .A DiLorenzo C; Dooley CP; Valenzuela JE. .I 200962 .U 90004792 .S Dig Dis Sci 9001; 34(10):1611-2 .M Esophagogastric Junction/*PH; Esophagus/PH; Human; Hydrostatic Pressure; Manometry. .T Hypertensive lower esophageal sphincter [editorial] .P EDITORIAL. .A Carey WD. .I 200963 .U 90004793 .S Dig Dis Sci 9001; 34(10):1613-4 .M Animal; Antigens/IM; Crohn Disease/*ET/IM/PP; Diet/*; Human; Intestinal Absorption; Milk/IM. .T Dietary antigens as aggravating factors in Crohn's disease [editorial] .P EDITORIAL. .A Harris ML; Bayless TM. .I 200964 .U 90004794 .S Dig Dis Sci 9001; 34(10):1615-6 .M Anemia, Hemolytic, Autoimmune/CO/TH; Case Report; Cyclophosphamide/*TU; Female; Granuloma, Giant Cell/CO/*DT; Human; Liver Diseases/CO/*DT; Middle Age; Prednisone/TU; Splenectomy. .T Cyclophosphamide therapy of idiopathic hepatic granulomatosis. .P JOURNAL ARTICLE. .W A 50-year-old woman presented with idiopathic hepatic granulomatosis and autoimmune hemolytic anemia. Splenectomy corrected the anemia, and the liver disorder responded to prednisone. However, her liver disease relapsed on four occasions when prednisone was tapered, including three episodes when hepatic granulomatosis was proven by biopsy. Cyclophosphamide therapy allowed prednisone withdrawal, and she has remained in clinical and biochemical remission for two years on a low dose of the drug. .A Longstreth GF; Bender RA. .I 200965 .U 90004795 .S Dig Dis Sci 9001; 34(10):1617-20 .M Acquired Immunodeficiency Syndrome/CO; Adult; Case Report; Female; Human; Male; Pancreatitis/*CI; Pentamidine/*AE; Pneumonia, Pneumocystis carinii/DT. .T Pentamidine-associated pancreatitis. .P JOURNAL ARTICLE. .W Two patients without risk factors or a prior history of pancreatitis developed acute pancreatitis soon after initiating pentamidine isethionate therapy for Pneumocystis carinii pneumonia associated with the acquired immunodeficiency syndrome. In both patients the pancreatitis improved following medication cessation. One patient did not redevelop pancreatitis when he subsequently received inhaled pentamidine. Review of the literature revealed five previously reported cases of this drug reaction. Pentamidine-associated pancreatitis appears to develop within three weeks of initiating therapy and after receiving more than 1 g in cumulative dosage. Glucose abnormalities, renal insufficiency, and non-specific abdominal pain may be early warning signs of pentamidine-associated pancreatitis. .A Schwartz MS; Cappell MS. .I 200966 .U 90004796 .S Dig Dis Sci 9001; 34(10):1621-3 .M Aged; Animal; Balantidiasis/DT/*PP; Balantidium; Case Report; Colitis/DI/PA/*PS; Doxycycline/TU; Human; Intestinal Polyps/PA/PS; Lung Diseases/*PP; Male; Zoonoses. .T Invasive balantidiasis presented as chronic colitis and lung involvement. .P JOURNAL ARTICLE. .W A unique case of chronic balantidiasis is described, presenting with chronic colitis and inflammatory polyposis of the rectum and sigmoid colon and an intrapulmonary mass. Histology of the colonic polyps showed Balantidium coli, and both Aspergillus and Balantidium coli were found in the aspirate of the pulmonary mass. The patient was treated with doxycycline HCl 100 mg/day for 10 days with complete clinical recovery and marked improvement of the endoscopic appearance of the colonic mucosa. .A Ladas SD; Savva S; Frydas A; Kaloviduris A; Hatzioannou J; Raptis S. .I 200967 .U 90004797 .S Dig Dis Sci 9001; 34(10):1624-8 .M Adult; Animal; Case Report; Crohn Disease/*DH/ET/RA; Human; Male; Milk/AE; Prednisone/TU. .T Treatment of patient with severe steroid-dependent Crohn's disease with nonelemental formula diet. Identification of possible etiologic dietary factor. .P JOURNAL ARTICLE. .A Ginsberg AL; Albert MB. .I 200968 .U 90004799 .S Dig Dis Sci 9001; 34(10):1637-9 .M Adult; Asthma/*ET; Cholecystokinin/PH; Eating; Esophagus/PH; Female; Gastrins/PH; Gastroesophageal Reflux/*CO; Gastrointestinal Hormones/*PH; Human; Hydrogen-Ion Concentration; Male; Middle Age; Motilin/PH; Neurotensin/PH; Peristalsis; Somatostatin/PH. .T Digestive peptides and asthma [letter] .P LETTER. .A Luo JY; Couture E; Chayvialle JA; Minaire Y. .I 200969 .U 90004800 .S Dig Dis Sci 9001; 34(10):1639-40 .M Antibodies/AN; Celiac Disease/*IM; Food Hypersensitivity/IM; Gliadin/*IM; Human; Malabsorption Syndromes/IM; Plant Proteins/*IM. .T Antigliadin antibody levels in symptomless celiac disease [letter; comment] .P COMMENT; LETTER. .A Frisoni M; Volta U; Valentini RA; Treggiari EA; Corazza GR; Gasbarrini G. .I 200970 .U 90004801 .S Dig Dis Sci 9001; 34(10):1640 .M Acute Disease; Human; Pancreatitis/DI/*EN. .T Reassessment of enzymes in acute pancreatitis [letter; comment] [see comments] .P COMMENT; LETTER. .A Christian RB; Greenberger NJ. .I 200971 .U 90004802 .S Dig Dis Sci 9001; 34(10):1640-2 .M Alkaline Phosphatase/BL; Antigens, Tumor-Associated, Carbohydrate/*BL; Bilirubin/BL; Cholestasis/*IM; Human. .T Serum levels of carbohydrate antigenic determinant (CA 19.9) in obstructive jaundice [letter] .P LETTER. .A Benamouzig R; Buffet C; Fourre C; Ink O; Moati F; Etienne JP. .I 200972 .U 90004803 .S Dig Dis Sci 9001; 34(10):1642-3 .M Gastric Emptying/*; Human; Posture/*. .T Thoughts on gastric emptying relative to posture [letter; comment] .P COMMENT; LETTER. .A Flick AL. .I 200973 .U 90004804 .S Diabetes Care 9001; 12(9):601-3 .M Adult; Analysis of Variance; Bulimia/*CO/PX; Depression; Diabetes Mellitus, Insulin-Dependent/CO/*PX; Feeding Behavior; Female; Human; Risk Factors. .T Binge eating and purging in young women with IDDM. .P JOURNAL ARTICLE. .W Case reports and empirical studies suggest that young women with insulin-dependent diabetes mellitus (IDDM) may be at high risk for developing eating disorders. In this study, self-reports of binge eating and purging from 59 IDDM women (aged 18-30 yr) were obtained. Most participants (58%) reported that they went on eating binges, and 12% met the DSM-III criteria for a diagnosis of bulimia. Nearly 40% admitted to controlling their weight by insulin purging, and 13.5% reported purging by other means. A group of bulimic participants had mean scores on an eating disorder questionnaire in the pathological range. Bulimic symptoms were positively related to reports of hospitalizations, episodes of ketoacidosis, and psychological symptoms. Implications of these results on the medical management of young women with IDDM are discussed. .A Stancin T; Link DL; Reuter JM. .I 200974 .U 90004807 .S Diabetes Care 9001; 12(9):615-22 .M Absenteeism; Adult; Attitude to Health/*; Case-Control Studies; Cohort Studies; Comparative Study; Diabetes Mellitus, Insulin-Dependent/*/PX; Employment/*; Family; Handicapped; Human; Occupations; Personnel Management/*; Personnel Selection/*; Questionnaires; Regression Analysis; Support, U.S. Gov't, P.H.S.. .T Employment spectrum of IDDM. .P JOURNAL ARTICLE. .W Occupational issues in 158 insulin-dependent diabetes mellitus (IDDM) individuals and 158 matched nondiabetic siblings were examined in a case-control design to evaluate the role of diabetes in the employability of people with IDDM. Overall, the IDDM cases were more likely to report refusal for a job at some point in their lives (56 vs. 42%, P = .02) than were the nondiabetic control siblings. Surprisingly, individuals who told job interviewers about their diabetes were more likely to report job refusal than their siblings (64 vs. 42%, P = .005), whereas individuals who did not mention their diabetes reported rates of refusal similar to their siblings (44 vs. 41%). IDDM cases were also less likely to be employed full time compared with siblings (55 vs. 73%, P = .001). Reduced employment in IDDM respondents was related to work disability. Reported work disability was more than seven times greater in the IDDM than the sibling group. The presence of diabetic complications was the primary factor related to work disability. Although 13% of IDDM respondents were unable to work because of disability, absenteeism among IDDM cases currently working did not differ from that of the nondiabetic siblings. Diabetes was not significantly associated with career levels or household income levels reported by the IDDM group. Disability, however, had a strong detrimental influence on these variables. The results suggest that hiring practices by employers may still be discriminatory toward individuals with IDDM. Once hired, the employment experiences of the IDDM population appear to be similar to the experiences of the nondiabetic population, provided the development of disabling diabetic complications has not taken place. .A Songer TJ; LaPorte RE; Dorman JS; Orchard TJ; Becker DJ; Drash AL. .I 200975 .U 90004809 .S Diabetes Care 9001; 12(9):630-5 .M Diabetes Mellitus, Non-Insulin-Dependent/*CO/PP; Female; Heart/*PP/RI; Heart Ventricle/PP; Human; Male; Middle Age; Myocardial Infarction/CO/*PP/RI; Regression Analysis. .T Left ventricular regional function after acute anterior myocardial infarction in diabetic patients. .P JOURNAL ARTICLE. .W To elucidate the pathophysiological role of diabetes mellitus in determining the left ventricular regional function of the noninfarcted area, 55 patients with acute Q wave anterior myocardial infarction (MI) were studied. The regional ejection fraction of the noninfarcted area was obtained by radionuclide angiocardiography and was used to estimate the left ventricular regional function of the noninfarcted area. Multiple regression analysis was performed to determine the important variables contributing to the regional ejection fraction based on 10 clinical variables: age, sex, QRS score, diabetes mellitus, hypertension, smoking, postinfarction angina, body mass index, serum cholesterol, and coronary atherosclerosis. A high QRS score (P less than .001) and the association of diabetes mellitus (P less than .05) were the important factors contributing to regional left ventricular dysfunction. The regional ejection fraction and QRS score had an inverse linear relationship in the diabetic and nondiabetic groups, and the regional ejection fraction was significantly lower in diabetic patients at every QRS score (P less than .05). The association of hypertension, severity of coronary atherosclerosis, serum cholesterol level, age, and body mass index did not differ between diabetic and nondiabetic patients, which indicates that diabetes mellitus was not mediated through these atherogenic traits. Thus, diabetes mellitus is another discrete cause of regional left ventricular dysfunction of the noninfarcted area after acute MI. .A Takahashi N; Iwasaka T; Sugiura T; Hasegawa T; Tarumi N; Kimura Y; Kurihara S; Onoyama H; Inada M. .I 200976 .U 90004810 .S Diabetes Care 9001; 12(9):636-40 .M Adult; Diabetes Mellitus, Insulin-Dependent/*PP; Diabetes Mellitus, Non-Insulin-Dependent/*PP; Diabetic Neuropathies/*DI/PP; Female; Human; Male; Neurologic Examination; Pain/PP; Reference Values; Sensory Thresholds/*; Support, Non-U.S. Gov't. .T Mapping diabetic sensory neuropathy by current perception threshold testing. .P JOURNAL ARTICLE. .W Detailed clinical neurological examinations were conducted on 44 nondiabetic volunteers and 59 diabetic subjects. The examinations focused particularly on sensory symptomatic and physical evaluation. Standardized assessment of symptoms and physical testing of light touch, pain, vibratory, and thermal sensation was performed at the hand, wrist, elbow, foot, ankle, and knee. A total symptom score and physical score were defined by summing test scores at each site. Current perception threshold (CPT) testing that used constant sine-wave-alternating current was conducted at the same anatomic sites. CPT correlations with the physical score gave r values of .55 for 5 Hz, .60 for 250 Hz, and .62 for 2000 Hz (n = 618). Correlations with the symptom score were not as strong: r = .45 for 5 Hz, .46 for 250 Hz, and .51 for 2000 Hz. The correlation with symptom score was due primarily to a strong relationship for the symptom of numbness (r = .53 for all 3 frequencies). Correlations with pain and paresthesia were much lower. CPTs for diabetic subjects at the three frequencies were higher at most locations than for the nondiabetic volunteers. However, CPTs were no different from normal values in diabetic subjects without evidence of neuropathy. CPT testing appears to be a useful technique for assessment of diabetic sensory neuropathy. .A Rendell MS; Dovgan DJ; Bergman TF; O'Donnell GP; Drobny EP; Katims JJ. .I 200977 .U 90004813 .S Diabetes Care 9001; 12(9):653-5 .M Clothing/*; Comparative Study; Diabetic Neuropathies/*TH; Female; Foot/*; Human; Male; Neural Conduction; Perception; Pressure; Support, Non-U.S. Gov't. .T Use of experimental padded hosiery to reduce abnormal foot pressures in diabetic neuropathy. .P JOURNAL ARTICLE. .W High pressures under the feet of diabetic patients with neuropathy are associated with the development of plantar ulceration. The aim of management is the reduction of such stresses with orthoses and insoles. An American hosiery manufacturer has developed socks designed to reduce stress on athletes' feet, and we report a preliminary evaluation of this technique in the reduction of elevated plantar pressure in 27 neuropathic diabetic patients. With a computerized optical pedobarograph, three footsteps on each side were recorded under three conditions: 1) barefoot, 2) wearing the patients' own hosiery, and 3) wearing experimental patented padded hosiery. The patients' own hosiery did not have a significant effect on plantar pressure, but the experimental hosiery reduced both peak forefoot pressure and the area under the time-pressure curve (P less than .001) by a mean of 26 and 29%, respectively. We conclude that the experimental hosiery is effective in reducing vertical pressures under the diabetic foot and, in conjunction with established orthotic techniques, may be a useful addition to the treatment of the diabetic patient at risk for foot ulceration. .A Veves A; Masson EA; Fernando DJ; Boulton AJ. .I 200978 .U 90004815 .S Diabetes Care 9001; 12(9):659-60 .M Automobile Driving; Diabetes Mellitus, Insulin-Dependent/*; Employment/*; Government Agencies; Human; Prejudice/*; United States; Voluntary Health Agencies. .T Diabetics need not apply [editorial] [see comments] .P EDITORIAL. .A Fisher JN. .I 200979 .U 90004816 .S Diabetes Care 9001; 12(9):661 .M Comparative Study; Human; Hyperbaric Oxygenation/*; Oxygen/BL; Oxygen Inhalation Therapy/*; Partial Pressure. .T Clearing an oxygen confusion [letter; comment] .P COMMENT; LETTER. .A Hill RK Jr. .I 200980 .U 90004817 .S Diabetes Care 9001; 12(9):661-3 .M Biological Markers/*BL; Human; Insulinoma/BL/*DI; Islet Cell Tumor; Pancreatic Neoplasms/BL/*DI; Proinsulin/*BL. .T Proinsulin levels and insulinomas [letter; comment] .P COMMENT; LETTER. .A Service FJ. .I 200981 .U 90005108 .S Endocrinology 9001; 125(4):1749-53 .M Endocrinology/*; Evaluation Studies; Periodicals/*; Research Design; Societies, Medical/*; Statistics/*. .T Report on statistical quality of Endocrine Society Journals. .P JOURNAL ARTICLE. .A Hawkins D; Conaway M; Hackl P; Kovacevic M; Sedransk J; Woodworth G; Bosch R; Breen C. .I 200982 .U 90005109 .S Endocrinology 9001; 125(4):1754-60 .M Animal; Body Weight; Calcitonin/*BL; Dose-Response Relationship, Drug; Estradiol/*PD; Female; Injections; Liver/AH; Male; Organ Weight; Salmonidae/*BL; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T 17 beta-estradiol increases plasma calcitonin levels in salmonid fish. .P JOURNAL ARTICLE. .W The functional role of calcitonin in teleost fish is in question. Data on the role of calcitonin in calcium regulation are inconsistent, and while a participation in some aspects of sexual maturation has been strongly indicated, the exact function is not known. To establish if there exists a functional relationship between 17 beta-estradiol (E2) and calcitonin in salmonid species, rainbow trout (Oncorhynchus mykiss), Atlantic salmon (Salmo salar), and coho salmon (Oncorhynchus kisutch) were injected ip with a single or repeated doses of E2. It is concluded that E2 treatment increases plasma calcitonin levels directly or indirectly, and that it is possible that E2 is responsible for the rise in calcitonin levels during late sexual maturation of female salmonids. In accord with earlier studies, no correlation was found between changes in calcitonin levels and free plasma calcium levels. It seems clear that changes in free plasma calcium levels are not the primary cause of the plasma calcitonin changes in teleost fish. It is possible that calcitonin is involved in mobilizing calcium or directing its mobilization by protection of certain calcium pools during vitellogenesis. However, the increase in calcitonin occurs so close to ovulation that a reproductive role other than a calcium regulatory one is likely. The possibility of transfer of calcitonin itself to the developing oocytes and a subsequent role in embryonic development must also be considered. .A Bjornsson BT; Haux C; Bern HA; Deftos LJ. .I 200983 .U 90005110 .S Endocrinology 9001; 125(4):1761-5 .M Amino Acids/AD; Animal; Colon; Comparative Study; Dogs; Duodenum; Eating; Fatty Acids/AD; Gastrointestinal Hormones; Glucose/AD; Infusion Pumps; Peptides/BL/*ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T A comparison of intraduodenally and intracolonically administered nutrients on the release of peptide-YY in the dog. .P JOURNAL ARTICLE. .W The objective of this study was to compare the effects of various nutrients (fats, proteins, amino acids, and carbohydrates), given directly into the duodenum or the colon, on the release of peptide-YY (PYY) in conscious dogs. As reported previously, this study showed that plasma levels of PYY increased significantly (P less than 0.05) within 15 min in response to an oral mixed meal. Intraduodenal (ID) administration of a fatty acid (oleic acid; 100 mmol/L; 100 ml/h) stimulated a robust release of PYY, whereas ID administration of an amino acid mixture (phenylalanine plus tryptophan; 100 mmol/L each; 100 ml/h), glucose (1 g/kg), or a liver extract (10%; 100 ml/h) failed to elevate plasma levels of PYY. ID administration of glucose at 2 g/kg caused a mild but significant elevation in plasma PYY levels. Intracolonic administration of saline, a fatty acid, an amino acid mixture, glucose, or a liver extract significantly stimulated PYY release. This study suggests that as chyme moves from the stomach to the proximal bowel, fat is the primary constituent of food that stimulates the prompt release of PYY. However, unabsorbed nutrients can release PYY by a direct contact with the PYY-containing cells lining the intestinal lumen of the terminal ileum, colon, and rectum. Both mechanisms probably participate in the release of PYY. .A Greeley GH Jr; Hashimoto T; Izukura M; Gomez G; Jeng J; Hill FL; Lluis F; Thompson JC. .I 200984 .U 90005111 .S Endocrinology 9001; 125(4):1766-73 .M Animal; Estrone/UR; Estrus/ME; Female; Gonadotropins/BL/*SE; LH/ME; Macaca/*PH; Macaca mulatta/ME/*PH; Osmolar Concentration; Ovum Implantation/*; Pregnancy/ME; Pulsatile Flow; Support, U.S. Gov't, P.H.S.. .T Absence of regular pulsatile gonadotropin secretion during implantation in the rhesus macaque. .P JOURNAL ARTICLE. .W The secretory response of the primate corpus luteum (CL) to CG after implantation suggests that gonadotropin receptors are not depleted despite increasing CG production and continuous elevated tropic stimulation. Such continuous stimulation is known to cause down-regulation of receptors in other tissues. To determine if CG secretion is intermittent during the initial stages of CL rescue, we assessed the secretory pattern of CG during the periimplantation period by collecting frequent (4/h) blood samples in two studies (for 4 h on 3 separate days between days 8-13, or for 2 separate 13-h sequences between days 10-15 postovulation) in 13 chair-adapted females. Day 0 of gestation was defined as the day of ovulation, as estimated by peak urinary estrone conjugate excretion in females mated on days 9, 11, and 13 of the menstrual cycle. Hormone concentrations were measured by either RIA [irFSH; estradiol and progesterone (P)] or Leydig cell bioassay (bioLH or bioCG). In the first study, 4 of 6 females conceived, and the mean for bioLH was not significantly elevated until days 12-13. In the second study, 5 of 7 females conceived, and the episodic secretory pattern of circulating pituitary bioLH typically observed in cycling females (2.7 +/- 0.3 peaks/13 h) was replaced by a relatively nonpulsatile, but steadily increasing profile during days 12-15 of gestation (1.5 +/- 0.4 peaks/13 h). Although occasional large fluctuations in bioLH/CG and P were noted, the bioLH/P peaks were less congruent than those in nonfertile cycles, and there was no diurnal pattern in the secretion of either hormone. In contrast, irFSH concentrations did not fluctuate and were similar in the two groups of females [2.93 +/- 0.28 vs. 2.34 +/- 1.7 ng/ml (mean +/- SEM)]. These data demonstrate that 1) a steady, gradually increasing secretory pattern of CG is associated with rescue of the CL; 2) the circulating profile of CG during the periimplantation interval is not consistently episodic and does not support the hypothesis that intermittent CG release prevents LH/CG receptor down-regulation in the CL during early pregnancy; 3) increased bioLH/CG levels during conceptive cycles in rhesus monkeys are not detected until days 12-13 after the midcycle bioLH peak; 4) irFSH patterns on pooled aliquots appear to be uninformative with regard to gonadotropin dynamics in early pregnancy; and 5) urinary estrone conjugate measurements provide a practical method for the precise timing of infrequent events, such as implantation, in the laboratory macaque. .A Monfort SL; Hess DL; Hendrickx AG; Lasley BL. .I 200985 .U 90005112 .S Endocrinology 9001; 125(4):1774-82 .M Animal; Blotting, Northern; Chromatography, Gel; Comparative Study; Immunohistochemistry; Mice; Peptides/AN; Pro-Opiomelanocortin/*GE/ME; Protein Processing, Post-Translational/*; Radioimmunoassay; Rats; Somatotropin/*SE; Support, U.S. Gov't, P.H.S.; Transfection/*; Tryptophan/DU; Tumor Cells, Cultured/ME/*PH/SE. .T Posttranslational processing of transfected mouse pro-adrenocorticotropin/endorphin in rat growth hormone-secreting tumor cells. .P JOURNAL ARTICLE. .W Pro-ACTH/endorphin (PAE; also POMC) is a hormone precursor that contains potential sites for endoproteolytic cleavage, glycosylation, phosphorylation, acetylation, sulfation, and amidation. Different sets of these sites are used in different neuroendocrine tissues. To learn more about the factors influencing the posttranslational processing of peptide hormone precursors, the cDNA for mouse PAE was cloned into a metallothionein expression vector. Two lines of rat GH-secreting tumor cells (GH3 and GC) were transfected with the resulting expression plasmid, and stable PAE-producing clones were isolated. Both GH3 and GC cells gave rise to clones in which about 75% of PAE was endoproteolytically processed. Mol wt distributions of PAE peptides were similar in cell extracts and medium, indicating that processing was not the result of extracellular proteases. The identity of immunoprecipitated molecules was confirmed by analysis of tryptic digests by reverse phase HPLC. Amidated forms of joining peptide were detected in the transfected cells by immunocytochemistry, adding evidence that GH-producing tumor cells can perform endoproteolysis, exoproteolysis, and alpha-amidation of the PAE precursor. One of the two forms of joining peptide from cell extracts was also shown to comigrate during reverse phase HPLC with authentic alpha-amidated mouse joining peptide. Comparisons of Northern analyses and peptide synthetic rates suggested that PAE mRNA was used for synthesis of PAE more efficiently in corticotropes than in the transfected GC cells. .A Cullen EI; Mains RE. .I 200986 .U 90005113 .S Endocrinology 9001; 125(4):1783-8 .M Animal; Carcinoma/ME/PA; Dose-Response Relationship, Drug; Human; Iodides/ME; Rats; Receptors, Endogenous Substances/*ME; Thyroid Gland/CY/*ME; Thyroid Neoplasms/ME/PA; Thyrotropin/PD/*PH; Tumor Cells, Cultured; Tumor Necrosis Factor/ME. .T Characterization of tumor necrosis factor-alpha receptors in human and rat thyroid cells and regulation of the receptors by thyrotropin. .P JOURNAL ARTICLE. .W Administration of recombinant human tumor necrosis factor-alpha (TNF) to rats and mice produces a model of nonthyroid illness in which there is impairment of hypothalamic-pituitary thyroid function, including reduced serum concentrations of T4 and T3, reduced thyroid radioiodine uptake, and reduced response to TSH. In this study, we tested the binding and effects of TNF on FRTL-5 cells and on four human thyroid carcinoma cell lines. The TSH-stimulated [125I]iodide uptake by FRTL-5 cells was inhibited by TNF in a dose-dependent manner. The four human thyroid carcinoma cell lines (NPA, MRO, ARO, WRO) have TSH receptors but did not respond to TSH in regard to iodide uptake and thymidine incorporation. Both human thyroid carcinoma cells and FRTL-5 cells contain specific receptors for TNF. Scatchard analysis showed that the receptor numbers and dissociation constants in human thyroid carcinoma cells and FRTL-5 cells were, respectively; 2.4 x 10(4), 5.4 nM (WRO); 8 x 10(3), 3.4 nM (MRO); 4 x 10(3), 1 nM (ARO); 7 x 10(3), 1 nM (NPA); 3 x 10(3), 1 nM (FRTL-5), and 9 x 10(3), 1 nM (FRTL-5 cells treated with TSH). The results indicate that TNF affects thyroid cell function through binding to the TNF receptor and that the number of TNF receptors is regulated by TSH. .A Pang XP; Hershman JM; Chung M; Pekary AE. .I 200987 .U 90005114 .S Endocrinology 9001; 125(4):1789-94 .M Adenosine Cyclic Monophosphate/ME; Androgens/PD/*PH; Bone and Bones/*DE/ME/PA; Culture Media; Cycloheximide/PD; Hormones/PD; Human; Neoplasm Proteins/*PD; Parathyroid Hormones/*PD; Pertussis Toxins/PD; Support, U.S. Gov't, P.H.S.; Time Factors; Tumor Cells, Cultured. .T Direct modulation by androgens of the response of human bone cells (SaOS-2) to human parathyroid hormone (PTH) and PTH-related protein. .P JOURNAL ARTICLE. .W We have reported previously that 17 beta-estradiol (E2) inhibits selectively the cAMP response to human (h) PTH and PTH-related protein (hPTHrP), but not to vasoactive intestinal peptide, in human osteoblast-like cells (SaOS-2). We have now extended these studies to investigate the actions of androgens on hPTH-stimulated accumulation of cAMP, and on the roles of new protein synthesis and pertussis toxin (PTox) substrates in the actions of steroid hormones on SaOS-2 cells. Pretreatment with testosterone (T) or 5 alpha-dihydrotestosterone (5 alpha-DHT) for 4-12 h at concentrations of 10(-12) to 10(-8) M inhibited significantly the cAMP response to hPTH by up to 50-70% of control. Like E2, the actions of T and 5 alpha-DHT were selective for hPTH or hPTHrP; there was no inhibition of the stimulatory action of vasoactive intestinal peptide. Two related steroids, 5 beta-DHT and 17 alpha-epitestosterone, did not inhibit the action of hPTH. Pretreatment of cells with cycloheximide, under conditions which inhibited protein synthesis by greater than 90%, reduced the cAMP response to hPTH but did not block the further inhibitory actions of E2, T, or 5 alpha-DHT. Pretreamtent of cells with PTox (100 ng/ml) for 24 h, enhanced the accumulation of cAMP stimulated by hPTH consistent with an action of PTox on Gi; however, the inhibitory actions of E2, T, and 5 alpha-DHT on PTH-stimulated cAMP accumulation were not attenuated by PTox. We conclude that androgens, as well as estrogens, act directly on human bone cells to modulate selectively an early effect of hPTH. The inhibitory actions of these steroid hormones do not appear to depend on new protein synthesis and may not involve a functionally active PTox substrate, presumably Gi. .A Fukayama S; Tashjian AH Jr. .I 200988 .U 90005118 .S Endocrinology 9001; 125(4):1821-8 .M Androgens/*PD; Animal; Autoradiography; Estradiol/*PD; Female; Male; Nucleic Acid Hybridization; Pituitary Gland, Anterior/*ME; Prolactin/*GE; Rats; Rats, Inbred Strains; RNA, Messenger/*AI/ME; Sex Characteristics; Support, Non-U.S. Gov't. .T Inhibitory effect of androgen on estrogen-induced prolactin messenger ribonucleic acid accumulation in the male rat anterior pituitary gland. .P JOURNAL ARTICLE. .W Estrogens are known to exert specific stimulatory effects on basal and dopamine-inhibited PRL secretion and synthesis as well as on PRL gene expression. However, dihydrotestosterone (DHT) and progesterone (P), although inactive alone, can reverse the effect of 17 beta-estradiol (E2) on PRL release both in vivo and in vitro. Using castrated male rats, we have studied the effect of E2 (0.25 micrograms), P (2 mg), or DHT (100 micrograms) administered twice daily for 14 days alone or in combination on pituitary PRL mRNA levels measured by quantitative in situ hybridization. Treatment with E2 increased the accumulation of PRL mRNA by about 2.6-fold. Administration of P or DHT alone failed to modify PRL mRNA concentrations. However, DHT could prevent by 80% the stimulatory effect of E2 on PRL mRNA levels. Similar results were obtained by dot blot hybridization assay. The effects of sex steroids on PRL mRNA were closely paralleled to pituitary PRL content measured by RIA. The present data demonstrate that the effect of sex steroids on immunodetectable PRL result from a modulation of PRL mRNA accumulation. The sexual dimorphism observed in pituitary PRL content results from a 3.5-fold greater accumulation of PRL mRNA in intact females than in male rats. These results also clearly show that quantitative in situ hybridization is a powerful tool in the investigation of the regulation of gene expression in addition to providing valuable information on the localization of specific mRNA. .A Tong Y; Simard J; Labrie C; Zhao HF; Labrie F; Pelletier G. .I 200989 .U 90005119 .S Endocrinology 9001; 125(4):1829-43 .M Animal; Hamsters; Male; Mesocricetus; Microscopy, Electron; Sertoli Cells/*CY/ME/PH; Sex Hormones/BL/*ME; Spermatogenesis/*PH; Support, U.S. Gov't, P.H.S.; Testis/*CY/ME. .T Correlative morphology and endocrinology of Sertoli cells in hamster testes in active and inactive states of spermatogenesis. .P JOURNAL ARTICLE. .W The seasonally breeding golden (Syrian) hamster, which exhibits photoperiod-dependent transitions between active and inactive states of spermatogenesis, was used as a model to study Sertoli cell structure in the two extreme phases of gonadal activity. The structural parameters of the Sertoli cell and its subcellular organelles were assessed using accepted stereological procedures during active and inactive states of spermatogenesis, and the results correlated with a battery of endocrine parameters obtained from the same animals. Short photoperiod-induced testicular involution was associated with a significant decrease in virtually all morphological parameters of the Sertoli cell, including a dramatic decrease in the volumes and surface areas of the Sertoli cells and their major subcellular organelles. Sertoli cell size and surface area were significantly and positively correlated with the testicular weight, volume of the seminiferous tubule, tubular lumena, tubule diameter, and germ cell numbers. Similar correlations were recorded between the number of germ cells and nearly all subcellular parameters of the Sertoli cell. Only those structural elements that are related to degredative processes (lysosomes and lipid) did not show significant volumetric differences between gonadally active and inactive animals. The observed changes in the structural parameters of the Sertoli cells were significantly correlated with the reduction in plasma levels of FSH, LH, and testosterone and intratesticular levels of testosterone. Exposure of hamsters to a short photoperiod was also associated with an increase in concentration (femtomoles per mg protein), but a decrease in the total content (femtomoles per testis) of testicular FSH receptors. The dissociation of changes in the content and concentration of FSH receptors appears to be related to changes in basal compartment plasma membrane surface areas of the Sertoli cells during testicular regression. The striking changes in Sertoli cell morphology between active and inactive states of spermatogenesis are structural manifestations of alterations in the function of these cells in response to the concomitant endocrine changes in the testis and indicate a virtual shut-down of Sertoli cell function during short photoperiod-induced testicular regression. .A Hikim AP; Amador AG; Klemcke HG; Bartke A; Russell LD. .I 200990 .U 90005120 .S Endocrinology 9001; 125(4):1844-56 .M Animal; Hamsters; Leydig Cells/*CY/ME/PH; Male; Mesocricetus; Microscopy, Electron; Receptors, LH/ME; Sex Hormones/*ME; Support, U.S. Gov't, P.H.S.; Testis/CY/PH. .T Structure/function relationships in active and inactive hamster Leydig cells: a correlative morphometric and endocrine study. .P JOURNAL ARTICLE. .W Spermatogenesis can be turned on or off in the seasonally breeding golden (Syrian) hamster in a laboratory setting by exposure of animals to different photoperiod regimens. The present study provides the first detailed quantitative analysis of the subcellular features of hamster Leydig cells during active and inactive phases of spermatogenesis and correlates these features with the endocrine activity of the same animals. Conventional stereological principles and accepted morphometric techniques were used to determine changes in a variety of subcellular constituents of Leydig cells at the extreme phases of gonadal activity produced by maintaining adult hamsters in a long photoperiod (16 h of light, 8 h of darkness) or by exposing them to a short photoperiod (6 h of light, 18 h of darkness) for 12-13 weeks. Compared with Leydig cells from gonadally active animals, Leydig cells obtained from the regressed testis showed a significant reduction in the absolute volume of nearly all of its organelles, including nucleolus (77.0%), mitochondria (50.0%), total endoplasmic reticulum (ER) (86.4%; cisternal ER, 87.0%; tubular ER, 85.5%), lipid (84.2%), peroxisomes (82.5%), multi-vesicular bodies (71.9%), filament-rich area (95.5%), and Golgi complex (69.4%). There was also a significant reduction in organelle surface area, namely outer (76.5%) and inner (72.7%) mitochondrial membrane, total ER (85.0%), cisternal (85.3%) and tubular (84.4%) forms of ER, and Golgi complex (70.0%). The surface areas of the plasma membrane and nuclear membrane were also decreased by 58.3% and 33.7%, respectively. These results demonstrate that the short photoperiod-induced cellular inactivity of Leydig cells is associated with an overall diminution in the volume and surface area of all major organelles, not only those specifically associated with steroid biosynthesis. Virtually every structural parameter of the Leydig cell was significantly and positively correlated with plasma LH levels and with both plasma and testicular concentrations of testosterone. The total content of LH receptors per testis and per Leydig cell was reduced, but the concentration of receptors per unit area of the Leydig cell surface remained unchanged. Correlation of changes in hormonal status with alterations of all Leydig cell organelles suggests a general shut-down of cellular activity in the gonadally regressed animals, rather than a specific effect of pituitary hormones on selected cellular constituents. .A Hikim AP; Amador AG; Bartke A; Russell LD. .I 200991 .U 90005121 .S Endocrinology 9001; 125(4):1857-62 .M Animal; Cell Separation; Cell Survival; Female; Follicular Phase; Graafian Follicle/CY/*DE/ME; Inhibin/BI/*PD; Oocytes/PH; Proteins/*PD; Rats; Rats, Inbred Strains; Steroids/ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tissue Culture; Transforming Growth Factors/*PD. .T Effects of transforming growth factors and inhibin-related proteins on rat preovulatory graafian follicles in vitro. .P JOURNAL ARTICLE. .W In view of recent reports on ovarian production and action of transforming growth factors (TGFs) and inhibin-related proteins (inhibin, activin, and follistatin), we have examined the effects of these hormones on the function of preovulatory follicles in vitro. Individual preovulatory follicles were obtained from PMSG-treated rats and incubated with these hormones in the absence or presence of LH. Oocyte maturation and progesterone production were monitored. Treatment with TGF alpha alone, but not with TGF beta or inhibin-related proteins, mimicked the action of LH on oocyte maturation by inducing the resumption of meiosis in follicle-enclosed oocytes (56.6% and 80.6% oocytes resumed meiosis in the presence of 0.5 and 1.0 microgram/ml TGF alpha, respectively). In follicle cultures treated with LH to induce oocyte maturation, cotreatment with inhibin and TGF beta (30-50 ng/ml), but not other related hormones, partially inhibited LH-induced meiosis in follicle-enclosed oocytes (from 82% mature ova in the presence of LH to 51% and 55% mature ova with TGF beta and inhibin, respectively). In contrast to follicle cultures, none of the hormones tested significantly affected the spontaneous maturation of rat oocytes explanted from their follicles and cultured within their cumulus mass for 4 h. Treatment with TGF alpha, but not with TGF beta, inhibin, activin, or follistatin, stimulated progesterone production. The present study demonstrated that TGF alpha, like LH, induces oocyte maturation and progesterone production in preovulatory rat follicles. Furthermore, inhibin and TGF beta suppressed LH-induced resumption of meiosis in follicle-enclosed oocytes. Because these growth factors and inhibin-related proteins are synthesized by follicle cells, they may play important roles in regulating follicular development and activity. .A Tsafriri A; Vale W; Hsueh AJ. .I 200992 .U 90005122 .S Endocrinology 9001; 125(4):1863-9 .M p-Chlorophenylalanine/PD; Animal; Dose-Response Relationship, Drug; Ergolines/PD; Female; Fentanyl/*PD; Ketanserin/PD; Prolactin/AI/*ME/SE; Rats; Receptors, Endorphin/*PH; Serotonin/*ME/PD; Serotonin Antagonists/PD; Support, Non-U.S. Gov't. .T Fentanyl stimulates prolactin release through mu-opiate receptors, but not the serotonergic system. .P JOURNAL ARTICLE. .W Both serotonin (5-HT) and opiates exert a stimulatory effect on PRL secretion. Some evidence suggests that the action of opiates may be elicited through serotonergic neurons. We tested this hypothesis in the present study by evaluating the effect of perturbation of the serotonergic system on PRL secretion induced by fentanyl, a potent morphine-like analgesic. Female Sprague-Dawley rats ovariectomized for 3 weeks and given polyestradiol phosphate (0.1 mg/rat) for 1 week were used in the study. Fentanyl, at a dose of 20 micrograms/rat, induced significant PRL secretion that peaked at 10 min and lasted for more than 30 min. Pretreatment with naloxone (0.5 mg/kg BW, ip) did not block the acute phase of PRL secretion, but significantly lowered the PRL level at 30 min. Fentanyl at a smaller dose (5 micrograms/rat, iv) still induced significant PRL release 10, but not 30, min after injection. This effect was significantly blocked by pretreatment with the same dose of naloxone. On the other hand, whereas animals pretreated with ketanserin or LY53857 (both at a dose of 5 mg/kg BW, ip), two specific 5-HT2 receptor antagonists, had no effect on fentanyl-induced PRL secretion, the same treatment significantly blocked 5-HT-induced PRL secretion. Likewise, pretreatment with p-chlorophenylalanine (250 mg/kg BW, ip), a 5-HT synthesis inhibitor, for 2 days had no effect on the action of fentanyl, while 5-HT-induced PRL secretion was significantly augmented. We conclude that fentanyl acts through mu-opiate receptors to stimulate PRL secretion in a process that does not involve the serotonergic system. .A Pan JT; Teo KL. .I 200993 .U 90005123 .S Endocrinology 9001; 125(4):1870-6 .M Animal; Bone and Bones/*DE; Calcitriol/PD; Cartilage/CY/ME; Cells, Cultured; Drug Resistance; Estradiol/*PD; Male; Rats; Rats, Inbred Strains; Skull/CY/ME; Support, Non-U.S. Gov't; Testosterone/*PD; Vitamin D/*ME; Vitamin D Deficiency/PP. .T Modulation by vitamin D status of the responsiveness of rat bone to gonadal steroids. .P JOURNAL ARTICLE. .W We have previously demonstrated that gonadal steroids stimulate [3H]thymidine incorporation and creatine kinase specific activity in skeletal tissues. In the present study we report that in 20-day-old vitamin D-deficient Wistar-derived rats, 17 beta-estradiol (E2; 5 micrograms/rat) or testosterone (50 micrograms/rat) failed to stimulate [3H]thymidine incorporation into diaphyses of long bones and that the response to these hormones in terms of increased creatine kinase specific activity was less than half the value in normally fed rats. Two daily ip injections of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3; 0.5 ng/g BW], but not 24,25-(OH)2D3 (5 ng/g BW), partially restored the biological responses to E2 in bone of 21-day-old vitamin D-deficient female rats. Vitamin D deficiency did not impair the responsiveness to gonadal steroids in the epiphysis of long bones, uterus, or prostate, in contrast to its effect on diaphysis. In 21-day-old normally fed female rats, neither vitamin D metabolite enhanced the response to E2. When cultures of rat epiphyseal cells were treated daily for 5 days with either 1,25-(OH)2D3 (1 nM) or 24,25-(OH)2D3 (10 nM), followed by E2 (30 nM) for 24 h, creatine kinase activity was significantly higher than in cultures treated daily for 5 days with vehicle alone, and then with E2. The same treatment of rat embryo calvaria bone cells showed that 1,25-(OH)2D3, but not 24,25-(OH)2D3, significantly increased the creatine kinase activity response to E2. These findings suggest that vitamin D metabolites selectively affect the biological responses of skeletal tissues to gonadal steroids. .A Somjen D; Kaye AM; Harell A; Weisman Y. .I 200994 .U 90005124 .S Endocrinology 9001; 125(4):1877-88 .M Animal; Brain/*ME; Chromatography, Affinity; Corticotropin-Releasing Hormone/ME; Cross-Linking Reagents/PD; Glycoside Hydrolases/PD; Glycosylation; Lectins/DU; Male; Peptide Mapping; Pituitary Gland/*ME; Rats; Rats, Inbred Strains; Receptors, Neurohumor/*ME. .T Heterogeneity between brain and pituitary corticotropin-releasing factor receptors is due to differential glycosylation. .P JOURNAL ARTICLE. .W Chemical affinity cross-linking studies have identified brain and pituitary CRF receptors with similar pharmacological characteristics but different mol wts (anterior pituitary, 75,000; brain, 58,000). In order to determine whether the heterogeneous nature of CRF receptors was inherent in the protein, we examined the glycoprotein nature of both types of CRF receptors using lectin affinity chromatography and treatments with exo- and endoglycosidases. CRF receptors in both the cerebral cortex and anterior pituitary adsorbed to and specifically eluted from Concanavalin-A- and wheat germ agglutinin-immobilized lectin affinity columns, indicating that both forms of the receptor are glycoproteins containing complex and high-mannose carbohydrate moieties. Cerebral cortical CRF receptors were sensitive to both neuraminidase and alpha-mannosidase treatment while pituitary CRF receptors were only affected by neuraminidase treatment, suggesting that CRF receptors in brain and pituitary differed slightly in the nature of their glycosylation units. After treatment of cerebral cortical or anterior pituitary CRF receptors with the endoglycosidase, N-glycanase, the mol wts were markedly decreased; the mol wt of the anterior pituitary CRF receptor was decreased from 75,000 to approximately 40,000-45,000 while in a corresponding manner, the cortical receptor was decreased from 58,000 to approximately 40,000-45,000. Limited proteolysis after deglycosylation with N-glycanase using the proteinases Staphylococcus aureus V8 (S. aureus V8) or papain, generated virtually identical peptide fragments from anterior pituitary- or cerebral cortex- labeled CRF receptor proteins. In summary, these data support the hypothesis that the ligand binding subunit of the CRF receptor in both brain and pituitary resides on a polypeptide of 40,000-45,000 and appears to be identical in both tissues. Differences observed in the mobility of the two proteins were found to be due to differences in the posttranslational modification of the proteins in the two tissues. .A Grigoriadis DE; De Souza EB. .I 200995 .U 90005125 .S Endocrinology 9001; 125(4):1889-97 .M Adenosine Triphosphate/*PD; Animal; Calcium/*ME; Calcium Channel Blockers/PD; Carbachol/*PD; Cell Line; Cells, Cultured; Dogs; Enzyme Activation; Intracellular Membranes/*ME; Osmolar Concentration; Protein Kinase C/ME; Support, U.S. Gov't, P.H.S.; Thyroid Gland/CY/*ME; Thyrotropin/*PD. .T Intracellular Ca2+ mobilization by thyrotropin, carbachol, and adenosine triphosphate in dog thyroid cells. .P JOURNAL ARTICLE. .W The effect of TSH, carbachol (CC), and ATP on intracellular calcium concentration ([Ca2+]i) in primary cultures of dog thyroid cells was examined using the fluorescent Ca2+ indicator fura-2. TSH caused an increase in [Ca2+]i at 37 C, but not 22 C, while it increased cAMP formation in these cells at both 22 and 37 C. CC and ATP increased [Ca2+]i at both 22 and 37 C. The CC-induced increase in [Ca2+]i was under muscarinic receptor control, and it was biphasic, with an initial spike followed by a sustained increase at a lower level. TSH and ATP were weaker agonists compared to CC, since maximal doses of TSH (100-500 mU/ml) and ATP (100-500 microM) increased [Ca2+]i by 40-70% over basal levels, compared to a 2- to 4-fold increase in [Ca2+] induced by maximal doses of CC (10-50 microM). The TSH-induced increase in [Ca2+]i was transient, returning to basal levels within 1-2 min after application of the agonist. All three agents were able to transiently increase [Ca2+]i to be internal stores. In the presence of the inorganic Ca2+ channel blockers La3+, Ni2+, and Co2+, the peak [Ca2+]i change was little affected, while the persistent response to CC and ATP was blocked, indicating dependence of this phase on influx of Ca2+. Paradoxically, these channel blockers abolished the effect of TSH on [Ca2+]i. TSH stimulation of cAMP formation was also inhibited 80-90% by these blockers, but not in Ca2+-free/EGTA buffer. These results suggest that the Ca2+ channel blockers may have actions in addition to inhibition of Ca2+ entry in these cells. TMB-8 [8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate HCl] specifically blocked both the initial and sustained increase induced by CC, while having no effect on ATP or TSH-induced [Ca2+]i, suggesting that TMB-8 may not be a general antagonist of Ca2+ mobilization. Activators of protein kinase-C, such as phorbol esters or an analog of diacylglycerol, inhibited the [Ca2+]i rise induced by all the three agonists used, indicating a regulatory role of protein kinase-C activation on [Ca2+]i in these cells. In FRTL-5 cells, [Ca2+]i was also increased by TSH and ATP, but not by CC. ATP, however, was a more effective agonist than in dog thyroid cells, while TSH increased [Ca2+]i by a similar magnitude in both cell types. The results of the present study demonstrate that TSH, albeit of lesser potency than CC, increases [Ca2+]i by causing intracellular Ca2+ mobilization in cultured dog thyroid cells.(ABSTRACT TRUNCATED AT 400 WORDS) .A Rani CS; Schilling WP; Field JB. .I 200996 .U 90005126 .S Endocrinology 9001; 125(4):1899-903 .M Animal; Cattle; Cell Count/DE; Culture Media; Female; Follicular Fluid/PH; Hamsters; Inhibin/ME/*PD; Injections; Injections, Intraperitoneal; Male; Mesocricetus; Mice; Mice, Inbred Strains; Molecular Weight; Sertoli Cells/CY/ME; Spermatogonia/*CY; Spermatozoa; Testis/*CY. .T Inhibin reduces spermatogonial numbers in testes of adult mice and Chinese hamsters. .P JOURNAL ARTICLE. .W Bovine follicular fluid (bFF) injected ip in mice during 2 days (65,000 U inhibin/day, 1 U inhibin the activity in 1 micrograms bFF protein) caused a significant decrease in the numbers of A4, intermediate (In), and B spermatogonia to 91%, 74%, and 67% of the control values, respectively. The numbers of undifferentiated spermatogonia remained unchanged. These injections suppressed peripheral FSH levels to 6% of the control values, suggesting that FSH might be the modulator of the effects on spermatogenesis. However, in the Chinese hamster, intratesticular injections of bFF during 4 days (6500 U inhibin/day into one testis) also caused a significant decrease in the numbers of A3. In, B1, and B2 spermatogonia to 86%, 61%, 55%, and 94% of the control values, respectively. Similarly, treatment with a partially purified inhibin preparation from rat Sertoli cell-conditioned medium (rSCCM) during 4 days (Mono Q fraction; 1512 U inhibin/day; 37.8 micrograms protein) caused a significant decrease in the numbers of A3, In, B1, and B2 spermatogonia to 90%, 87%, 66%, and 93% of the control values, respectively. Treatment with a highly purified inhibin preparation from rSCCM during 4 days (30K inhibin; 750 U inhibin/day; 100 ng protein) significantly decreased the numbers of In and B1 spermatogonia to, respectively, 87% and 91% of the control values. These effects were limited to the testis into which the material was injected; the contralateral testis or testes injected with control fluid always showed normal numbers of spermatogonia. This implies that the effects on the seminiferous epithelium are not FSH mediated. Intratesticular injections of bFF or pure inhibin did not affect the number of undifferentiated spermatogonia. However, the Mono Q fraction caused a significant increase in the numbers of undifferentiated spermatogonia in stages IV-VII of the cycle, suggesting the presence of a mitogenic factor for undifferentiated spermatogonia in rSCCM which is not present or is counteracted in bFF. The results suggest that inhibin may have a role in the regulation of spermatogonial development in the adult animal. .A van Dissel-Emiliani FM; Grootenhuis AJ; de Jong FH; de Rooij DG. .I 200997 .U 90005129 .S Endocrinology 9001; 125(4):1921-31 .M Adrenocorticotropic Hormone/*SE; Angiotensin II/*PD; Animal; Argipressin/*PD; Drug Interactions; Kinetics; Osmolar Concentration; Oxytocin/*PD; Perfusion/MT; Pituitary Gland, Anterior/CY/*SE; Rats; Receptors, Angiotensin; Support, U.S. Gov't, P.H.S.. .T Kinetic actions and interactions of arginine vasopressin, angiotensin-II, and oxytocin on adrenocorticotropin secretion by rat anterior pituitary cells in the microperifusion system. .P JOURNAL ARTICLE. .W We have examined the actions and interactions of arginine vasopressin (AVP), angiotensin-II (AII), and oxytocin (OT) on the ACTH secretory response of dispersed rat anterior pituitary cells in a microperifusion system. There was a dose-dependent ACTH secretory response to a 3-min perifusion of AII which reached its maximum 10 sec after the cells were exposed to AII and fell rapidly to baseline within 2 min, despite continued infusion of AII. This brief spike type of pattern is similar to that produced by AVP, but different from the sustained plateau response induced by CRF. The threshold stimulating concentration of AII was about 10(-9) M; the maximally stimulating concentration was not defined, but was 10(-6) M or more. The initial ACTH response to OT was similar, but fell to a plateau 2 min after the cells were exposed to OT and remained constant until perifusion with OT was stopped, after which it fell rapidly to baseline. The threshold stimulating concentration of OT was 10(-8) M; the maximally stimulating concentration was not defined, but was 10(-6) M or more. The ACTH secretory response to 10(-8) M AII was greatly diminished when cells were exposed to 10(-6) AVP or 10(-6) M OT before AII infusion. However, prior exposure to AII had no effect on the magnitude of the ACTH secretory response to either AVP or OT. The effects of simultaneous perifusion of AII and AVP and of AII and OT were additive. When AVP and OT were perifused sequentially, the ACTH secretory response to the peptide that was infused second was completely abolished. Furthermore, the combination of AVP and OT stimulated no greater response than either agent alone. When cells were perifused with the combination of 10(-7) M OT and 10(-7)- to 10(-5)-M concentrations of two potent AVP V1 receptor antagonists, [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-(O-methyl)tyrosine]-Arg8-vasopressin and [1-deaminopenicillamine-2-(O-methyl)tyrosine]-Arg8-vasopressin, both phases of the response to OT were progressively and almost completely inhibited. The initial spike phase was inhibited at lower antagonist concentrations than the sustained plateau phase.(ABSTRACT TRUNCATED AT 400 WORDS) .A Watanabe T; Oki Y; Orth DN. .I 200998 .U 90005130 .S Endocrinology 9001; 125(4):1932-40 .M Albuminuria/CO; Angiotensin II/*ME; Animal; Body Weight; Diabetic Nephropathies/CO/*ME/PA; Dogs; DNA/ME; Enalapril/PD; In Vitro; Kidney/PA; Kidney Glomerulus/ME; Male; Nephrectomy; Organ Weight; Proteins/ME; Rats; Rats, Inbred Strains; Reference Values; Support, Non-U.S. Gov't. .T The role of angiotensin-II in progressive diabetic glomerulopathy in the rat. .P JOURNAL ARTICLE. .W The potential pathogenic role of angiotensin-II (AII) in early progressive diabetic and renal ablation-induced glomerulosclerosis was explored and compared in the Sprague-Dawley (SD) rat and the mongrel dog. Male SD rats were divided into control and streptozotocin-treated (65 mg/kg, iv) groups. Unilateral surgical nephrectomy (Nx) was performed in half of each group. Enalapril (E; 50 mg/liter in the drinking water) was administered to half of each subgroup. Enalapril (high E; 250 mg/liter) was given to another 13 streptozotocin rats. All diabetic rats were treated with sc NPH insulin (4 U/day), and blood glucose was 520 +/- 124 mg/dl (mean +/- SD). Microalbuminuria was measured by RIA in 24-h urine collections; wet kidney weights were compared. [125I]AII binding assays were performed on isolated glomeruli. In control rats the high affinity binding dissociation constant (Kd) was 0.59 +/- 0.15 nM (n = 26; mean +/- SD) and receptor number (Ro) was 732 +/- 195 fmol/mg glomerular protein. At 3 weeks, the diabetic glomerular AII receptor Kd was 0.38 +/- 0.07 nM (n = 6; P less than 0.02 vs. control) and Ro was 784 +/- 97 fmol/mg protein (P = NS vs. control); diabetic high E Kd was 0.39 +/- 0.06 nM (n = 6; P less than 0.02 vs. control), and Ro was 873 +/- 105 fmol/mg protein (P = NS vs. diabetes without E). By 10 weeks, a Kd of 0.49 +/- 0.12 nM (n = 32; P less than 0.01 vs. control) and a Ro of 780 +/- 174 fmol/mg protein (P = NS vs. control) were observed when all of the diabetic group data were pooled. Neither Nx nor low or high dose E altered Ro. This is evidence that intraglomerular AII levels are normal or reduced after diabetes, Nx, or both. In the diabetic group, low dose E partially prevented, and high E abolished, Nx-enhanced microalbuminuria and renal hypertrophy. In nine pancreatectomized insulin-treated mongrel dogs over a 12- to 24-month period, despite moderately poor glucose control (300 +/- 75 mg/dl) and combined unilateral Nx in five dogs (12 months), elevated microalbuminuria was not observed. [125I]AII binding to isolated normal and diabetic dog glomeruli revealed the Kd to be of low affinity (1.86 +/- 0.28 to 13.80 +/- 1.88 nM), identifying the presence of type B receptors. Hence, the SD rat and mongrel dog differ in susceptibility to glomerular AII receptor type and progressive diabetic glomerulopathy.(ABSTRACT TRUNCATED AT 400 WORDS) .A Whiteside CI; Thompson J. .I 200999 .U 90005132 .S Endocrinology 9001; 125(4):1951-8 .M Androgens/*BI; Animal; Biomechanics; Cell Differentiation/DE; Cholesterol Desmolase/ME; Female; Ovary/*CY/ME; Progesterone/BI; Steroid 17-Hydroxylase/ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Theca Cells/*CY/ME; Transforming Growth Factors/*PD. .T Transforming growth factor-beta promotes differentiation of ovarian thecal-interstitial cells but inhibits androgen production. .P JOURNAL ARTICLE. .W Evidence that transforming growth factor-beta (TGF beta) is produced by thecal-interstitial cells (TIC) has suggested the hypothesis that TGF beta may be an autocrine regulator of TIC function. The purpose of these studies is to begin to test this hypothesis. In the present experiments we tested the effects of TGF beta on steroid production by TIC isolated from the ovaries of hypophysectomized immature rats by Percoll gradient centrifugation. When TIC (10(4) viable cells/well) were cultured in serum-free medium (0.2 ml in 96-well plates), low amounts of androsterone (less than 4 ng/ml) were produced at 2, 4, and 6 days. TGF beta (0.01-100 ng/ml) did not change basal androsterone production. Treatment with LH (50 ng/ml) stimulated a 100-fold increase in androsterone at 2 days and 60-fold increases at 4 and 6 days. Concomitant treatment with TGF beta (10 ng/ml) caused a 65% inhibition (ED50 = 2.3 +/- 0.7 ng/ml) of androsterone production at each time period. Analysis of key steroid metabolites demonstrated that androsterone and androstenedione were inhibited equally, while progesterone was significantly increased (ED50 = 1.2 +/- 0.2 ng/ml). Time-course studies revealed that TGF beta alone did not alter progesterone production at 2 days, but markedly increased progesterone (10-fold) above control levels at 4 and 6 days. Dose-response experiments showed that TGF beta did not alter the sensitivity of the TIC to LH stimulation, indicating that LH activation of the intracellular signaling pathway was not blocked by TGF beta. Treatment with insulin-like growth factor-I (IGF-I) together with LH caused a synergistic increase in androsterone production. The synergistic stimulation of LH action by IGF-I could be blocked by TGF beta. Interestingly, TIC were more sensitive to TGF beta in the presence of IGF-I (ED50 = 0.18 +/- 0.04 ng/ml). In contrast, TGF beta enhanced progesterone production only at the highest dose of TGF beta (10 ng/ml). To further elucidate the mechanism of TGF beta action, the effects of TGF beta on the TIC content of 17 alpha-hydroxylase/C17-20 lyase (P450(17)alpha) and cholesterol side-chain cleavage (P450scc) were analyzed by immunoblotting. TGF beta alone or in combination with LH stimulated an increase in P450scc content, but did not alter P450(17 alpha content. These results lead us to conclude that 1) the TIC are targets for TGF beta; 2) IGF-I increases the sensitivity of TIC to TGF beta action; and 3) TGF beta acts directly on TIC to stimulate progesterone while inhibiting androgen production. .A Magoffin DA; Gancedo B; Erickson GF. .I 201000 .U 90005135 .S Endocrinology 9001; 125(4):1973-82 .M Animal; Calcium Channels/*ME/PH; Cell Survival; Cells, Cultured; Chickens; Dihydropyridines/PD; Electrophysiology; Female; Granulosa Cells/*ME; Progesterone/*BI; Support, Non-U.S. Gov't. .T T- and L-calcium channels in steroid-producing chicken granulosa cells in primary culture. .P JOURNAL ARTICLE. .W Steroidogenesis and other functions in granulosa cells are calcium dependent. Using the patch-clamp technique to record single ion channel activity, we have identified for the first time two kinds of calcium channels through which the divalent ion may enter chicken granulosa cells. The cells were maintained in primary culture whose basal and hormone-stimulated progesterone production was evaluated at different times in culture and at different temperatures. A small channel, with a conductance of 4-5 picosiemens (pS), had short openings and inactivated rapidly. A large channel had a conductance of 20-30 pS, a high activation threshold, and slow inactivation kinetics. The dihydropyridine compound Bay K-8644, a L-calcium channel agonist, significantly increased the activity of the large channel, and nifedipine, a dihydropyridine calcium channel blocker, inhibited it completely. Both types of channels were seen in functionally competent signal-responsive granulosa cells cultured for up to 48 h. Whether these channels are involved in steroidogenesis, protein production, and/or secretion remains to be established. .A Schwartz JL; Asem EK; Mealing GA; Tsang BK; Rousseau EC; Whitfield JF; Payet MD. .I 201001 .U 90005140 .S Endocrinology 9001; 125(4):2015-21 .M Adenine/AA/PD; Aminoglutethimide/PD; Animal; Anticholesteremic Agents/PD; Cholesterol/BL/*ME; Corpus Luteum/CY/*ME; Female; Intracellular Membranes/*ME; Lipoproteins, HDL/*ME; Osmolar Concentration; Ovary/ME; Progesterone/BL/ME; Rats; Support, U.S. Gov't, P.H.S.; Up-Regulation (Physiology)/*. .T Regulation of rat luteal cell high density lipoprotein receptors: up-regulation in response to changes in intracellular cholesterol concentration. .P JOURNAL ARTICLE. .W High density lipoprotein (HDL)-derived cholesterol is preferentially utilized by rat luteal cells for steroid synthesis. This process is mediated, at least in part, by the HDL receptor. The regulation of the HDL receptor by intracellular cholesterol concentration in the ovary was assessed in the present study. Superovulated rats were treated with 4-aminopyrozolo [3, 4-d] pyrimidine (4-APP), which inhibits lipoprotein synthesis by the liver, to determine the effects of reduced levels of intracellular cholesterol on HDL receptor expression. Pseudopregnant rats were treated with 4-APP or the vehicle on days 3, 4, and 5 of pseudopregnancy. On day 6 rats were killed and ovarian membranes isolated for binding studies. Treatment with 4-APP resulted in almost a 50% decrease in serum cholesterol level 24 h later. A similar effect was observed on the level of ovarian esterified cholesterol. The binding of apolipoprotein E-free HDL to ovarian plasma membranes increased up to 34%. The effects of increased intracellular cholesterol on HDL receptor binding was then determined. Pseudopregnant rats received two injections of aminoglutethimide or vehicle on day 5 of pseudopregnancy at 10 h intervals for a period of 20 h. Rats were decapitated 10 h after the second injection of aminoglutethimide, and [125I] HDL binding studies were performed in ovarian plasma membranes. The treatment increased ovarian free and esterified cholesterol 27% and 70%, respectively. The number of binding sites for HDL in ovarian membranes increased up to 31% in response to the treatment. The evidence suggests that the HDL receptor may play a dual role in HDL metabolism. The receptor may increase to promote influx of cholesterol when intraovarian cholesterol stores are reduced and to promote cholesterol efflux when stores of intraovarian cholesterol are increased. Thus, HDL receptor appears to play a crucial role in the regulation of ovarian cholesterol level. .A Talavera F; Menon KM. .I 201002 .U 90005141 .S Endocrinology 9001; 125(4):2022-7 .M Animal; Bone and Bones/AH/*DE; Bone Development/DE; Femur/GD; Male; Organ Weight/DE; Parathyroid Hormones/*PD; Peptide Fragments/*PD; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Time Factors. .T Comparison of the anabolic effects of synthetic parathyroid hormone-related protein (PTHrP) 1-34 and PTH 1-34 on bone in rats. .P JOURNAL ARTICLE. .W The objective of this study was to determine whether intermittent synthetic human PTH-related protein (PTHrP 1-34) will mimic the anabolic effect of PTH and increase bone mass in rats. Dose response experiments were done on young, male Sprague-Dawley rats given sc vehicle, human (h) PTH (1-34) at 8 micrograms/100 g or PTHrP (1-34) at 1-32 micrograms/100 g daily for 12 days or 26 days. On the last day, 3 h after injections, rats were killed and serum, femurs, and tibias harvested. Trabecular and cortical bone of distal half femurs were analyzed for calcium (Ca) and hydroxyproline content and dry weight. Tibia metaphyseal bone was analyzed using conventional histomorphometry techniques. Our results showed that low doses of PTHrP (1-34) did not increase bone mass or bone forming surfaces. After 12 days, PTH, at 8 micrograms/100 g, increased trabecular Ca, dry weight, and hydroxyproline by approximately 19%, 36%, and 53%, respectively, while the bone mass of PTHrP-treated rats was comparable to vehicle-treated rats. PTHrP at a higher dose of 32 micrograms/100 g, increased trabecular bone mass by 30-37%, compared to the 43-48% increase induced by PTH at 8 micrograms/100 g after 12 days. When treatment was extended to 26 days, PTHrP, at 16 micrograms/100 g, increased trabecular bone mass by 24-36%, respectively, compared to the 43-61% increase induced by PTH at 8 micrograms/100 g. Unlike PTH, which increased cortical bone mass by 15-25%, PTHrP increased cortical bone mass only at the highest dose tested, 32 micrograms/100 g. Bone forming surfaces but not bone apposition rate were increased by PTH and PTHrP while resorption measures remained comparable to control values. Although serum Ca and Pi remained in the physiological range for all rats, the values for PTHrP-treated rats were consistently higher. In conclusion, PTHrP (1-34) was less potent and less effective than PTH (1-34) in inducing an anabolic response in bone in vivo. .A Hock JM; Fonseca J; Gunness-Hey M; Kemp BE; Martin TJ. .I 201003 .U 90005144 .S Endocrinology 9001; 125(4):2041-8 .M Animal; Female; Molecular Conformation; Molecular Weight; Phosphorylation; Pituitary Gland/ME/UL; Prolactin/*BI/ME; Rats; Rats, Inbred Strains; RNA, Messenger/GE/ME; Subcellular Fractions/ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Translation, Genetic; Tumor Cells, Cultured/ME. .T Biosynthesis of the secreted 24 K isoforms of prolactin. .P JOURNAL ARTICLE. .W PRL exists within the mammotroph population in a number of different molecular forms. Several of these forms are best described as isoforms, as they have the same mol wt (24 K), but differ in their net charges. In this study we have used in vitro translation assays to ascertain the number of 24 K translation products of normal pituitary messenger RNA (mRNA), and, finding only one, have used both in vitro translation assays and subcellular fractionation to determine the intracellular site of the posttranslational modification of this single translation product. Translation of mRNA from normal pituitary tissue or GH3 cells resulted in the apparent production of a number of pre-PRLs, but in only a single rough microsome-processed form of PRL, 24 K isoform 2. Longer term translation assays utilizing a variety of isotopes failed to show any evidence for rough microsomal posttranslational modification of isoform 2. Subcellular fractionation, using a discontinuous sucrose gradient, however, produced a membrane-bound large secretory granule fraction which, when isolated, contained essentially only isoform 2, and which had the capacity to convert isoform 2 to isoforms 3 and 3' by posttranslational phosphorylation. .A Greenan JR; Balden E; Ho TW; Walker AM. .I 201004 .U 90005148 .S Endocrinology 9001; 125(4):2075-82 .M Animal; Bone Resorption/*PP; Cell Separation; Culture Media; Cycloheximide/PD; Osteoblasts/*ME/PH; Osteoclasts/PH; Parathyroid Hormones/*PD; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured. .T Partial characterization of a parathyroid hormone-stimulated resorption factor(s) from osteoblast-like cells. .P JOURNAL ARTICLE. .W PTH stimulates osteoblast-like cells to produce a product(s) capable of increasing cellular bone resorption. We have investigated this phenomenon using primary cultures of osteoblasts and the clonal osteoblast-like cell line ROS 17/2. Conditioned medium from PTH-stimulated populations of either culture increases bone resorption compared to conditioned medium measured in three independent assay systems; the isolated osteoclast assay system, elicited macrophages, and the fetal bone rudiment system. Characterization of the factor(s) of PTH-stimulated osteoblast-like cell (ROS 17/2) suggests that the compound(s) is not prostaglandin (no inhibition by indomethacin; not extractable in diethylacetate). Rather, it is heat and protease sensitive. In addition, secretion of the product is sensitive to cycloheximide. These findings lead us to the conclusion that the factor(s) is protein. Further work demonstrates the necessity for a divalent cation for retention of factor activity. Finally, we have estimated the molecular radius of the factor as about 110,000 daltons and perhaps a second at about 70,000 daltons using a sizing column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of [35S]methionine-labeled PTH-stimulated ROS culture supernatants reveals relatively increased secretion of proteins with these approximate molecular radii. .A Perry HM 3d; Skogen W; Chappel J; Kahn AJ; Wilner G; Teitelbaum SL. .I 201005 .U 90005149 .S Endocrinology 9001; 125(4):2083-91 .M Animal; Cells, Cultured; Cholesterol/BI; Mevalonic Acid/ME; Neuroglia/*ME; Phosphorus/ME; Pregnenolone/AA/*BI; Progesterone/*BI; Rats; Support, Non-U.S. Gov't. .T Neurosteroids: biosynthesis of pregnenolone and progesterone in primary cultures of rat glial cells. .P JOURNAL ARTICLE. .W Cells dissociated from newborn rat forebrains were established in long term primary cultures. The cultures were made up almost exclusively of oligodendrocytes and astrocytes, as confirmed by indirect immunofluorescence staining with monoclonal antibodies to galactocerebroside and glial fibrillary acidic protein, respectively. After 3 weeks of culture, the oligodendrocytes were also highly immunoreactive to monospecific polyclonal antibodies against cytochrome P450scc, an enzyme involved in the conversion of cholesterol to pregnenolone (P). Biosynthesis of [3H]cholesterol, [3H]P, and [3H]Pregn-5-ene-3 beta, 20 alpha-diol was demonstrated in these primary cultures by incubating cells with [3H]mevalonolactone in the presence of mevinolin and trilostane. The activity of the 2',3'-cyclic nucleotide 3'-phosphodiesterase enzyme, a documented indicator of oligodendrocyte differentiation, increased rapidly after day 10 of culture, together with the onset of steroid biosynthetic activity. Both reached a maximum at 3 weeks of culture and remained stable up to 6.5 weeks. In the absence of trilostane, [3H]P was converted by glial cell cultures to [3H]progesterone, [3H]5 alpha-pregnane-3,20-dione, and [3H]3 alpha-hydroxy-5 alpha-pregnan-20-one. The demonstration of P, pregn-5-ene-3 beta,20 alpha-diol, and progesterone synthesis by normal rat glial cells, once oligodendrocytes have undergone their differentiation process, brings additional support to the concept of "neurosteroids." .A Jung-Testas I; Hu ZY; Baulieu EE; Robel P. .I 201006 .U 90005151 .S Endocrinology 9001; 125(4):2103-10 .M Adenyl Cyclase/ME; Alkaline Phosphatase/ME; Animal; Cartilage/*CY/ME; Cell Differentiation/DE; Cholecalciferols/*PD; Clone Cells; Dexamethasone/*PD; Dinoprostone/PD; Parathyroid Hormones/PD; Time Factors. .T Effects of dexamethasone and vitamin D3 on cartilage differentiation in a clonal chondrogenic cell population. .P JOURNAL ARTICLE. .W We have investigated the regulation of chondroblast/chondrocyte differentiation using a unique clonal cell population, designated RCJ 3.1C5 (C5), which differentiates into discrete three-dimensional cartilage nodules when grown in the presence of 15% fetal calf serum. Histologically, the nodules resembled hyaline cartilage; they contained large rounded chondrocytes surrounded by a refractile matrix which stained intensely with Alcian blue, exhibited metachromasia after Toluidine blue staining, and stained with an antibody against type II collagen. The cartilage nodules that formed did not mineralize, despite the presence of organic phosphate in the culture medium. The synthetic glucocorticoid dexamethasone (DEX) increased the number of cartilage nodules formed in a dose-dependent manner (ED50, approximately 10(-9) M), with a maximal stimulatory dose of 10(-8) M. DEX had no effect on the population doubling time and saturation density. The effects of DEX on the number of cartilage nodules were similar whether it was added from the beginning of the culture period (starting during exponential growth) or at confluence. In contrast, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] inhibited cartilage nodule formation in a dose-dependent manner (IC50, approximately 5 x 10(-10) M), with maximum inhibition at 10(-7) M. In addition, 1,25-(OH)2D3 decreased cell proliferation and saturation density. Equimolar doses of the vitamin D3 metabolites 24,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 had no effect. C5 cells treated with 1,25-(OH)2D3 in the absence of DEX during the exponential growth phase exhibited a reduced capacity to form cartilage nodules upon subsequent exposure to DEX. At confluence, before cartilage nodules had formed, C5 cells responded to PTH and prostaglandin-E2 with increases in intracellular cAMP of about 10- and 95-fold respectively. After cartilage nodules were present, prostaglandin-E2 responsiveness decreased to about 25-fold, whereas there was no significant change in PTH responsiveness. DEX decreased the population alkaline phosphatase levels at all times measured, whereas 1,25-(OH)2D3 had a biphasic effect: an increase at 5 days in culture, followed by a decrease at later times in culture. These data indicate that the clonal cell line RCJ 3.1C5 is a useful model system in which to investigate cartilage differentiation. .A Grigoriadis AE; Aubin JE; Heersche JN. .I 201007 .U 90005152 .S Endocrinology 9001; 125(4):2111-7 .M Animal; Estradiol/*PD; Female; Follicular Phase/*; LH/*ME; Neurotensin/*GE; Peptide Fragments/*GE; Preoptic Area/*ME; Rats; RNA, Messenger/*ME; Support, U.S. Gov't, P.H.S.; Time Factors; Tissue Distribution. .T Estrogen induces neurotensin/neuromedin N messenger ribonucleic acid in a preoptic nucleus essential for the preovulatory surge of luteinizing hormone in the rat. .P JOURNAL ARTICLE. .W Ovarian steroids act on unidentified neurons to trigger preovulatory secretion of GnRH. In the rat, important steroid target cells reside in the anterior medial preoptic nucleus (AMPN), a sexually dimorphic structure essential for stimulatory effects of ovarian steroids on LH secretion. The AMPN contains neurotensin (NT)-immunoreactive neurons, and immunoneutralization of NT in the preoptic region markedly attenuates steroid-induced LH surges. Using probes derived from the rat gene that encodes NT and neuromedin N (NT/N), we investigated the ability of estrogen to influence NT/N mRNA levels in the AMPN. Ovariectomized rats were treated for 14 days with sham capsules or capsules that produce supraphysiological serum levels of 17 beta-estradiol (250 +/- 20 pg/ml). As determined by in situ hybridization, estradiol markedly altered the distribution of NT/N mRNA in the medial preoptic region, causing a striking increase in NT/N mRNA abundance specifically in the AMPN and adjacent medial preoptic nucleus (MPN). In contrast, estradiol caused no obvious changes in labeling in the lateral septum, diagonal band of Broca, bed nucleus of the stria terminalis, and lateral preoptic area. The distribution of NT/N mRNA in the AMPN of normal male rats closely resembled that in ovariectomized rats, where labeled cells were rarely observed. Microdissection and S1 nuclease protection analysis were used to quantitate the effect of estradiol on NT/N mRNA levels. Supraphysiological estradiol treatment for 14 days caused a 3.4-fold increase (P less than 0.0002) in NT/N mRNA levels in the combined AMPN/MPN, whereas levels in the central amygdaloid nucleus remained constant, providing further evidence of regional specificity. Forty-eight hours of estradiol treatment, at concentrations (60 +/- 1 pg/ml) similar to those observed on the morning of proestrus, caused a 1.8-fold increase (P less than 0.001) in NT/N mRNA levels in the AMPN/MPN, indicating that the time course of NT/N mRNA induction by estrogen is compatible with events of the normal estrous cycle. Together with previous findings, our results strongly suggest that NT neurons mediate, directly or indirectly, stimulatory effects of ovarian steroids on GnRH secretion. .A Alexander MJ; Dobner PR; Miller MA; Bullock BP; Dorsa DM; Leeman SE. .I 201008 .U 90005153 .S Endocrinology 9001; 125(4):2118-26 .M Animal; Autoradiography; Cells, Cultured; Collagen/*BI; Dose-Response Relationship, Drug; DNA/*BI; Fibroblast Growth Factor/*PD; Heparin/PD; Parietal Bone/CY/*ME; Procollagen/CL/GE; Proline/ME; Proteins/BI; Rats; Support, U.S. Gov't, P.H.S.; Thymidine/ME. .T Effects of fibroblast growth factors on deoxyribonucleic acid and collagen synthesis in rat parietal bone cells. .P JOURNAL ARTICLE. .W Acidic fibroblast growth factor (aFGF) and basic FGF (bFGF) are related molecules that are extractable from bone matrix and may be important in the maintenance of normal bone physiology. The influence of each agent on DNA and protein synthesis was studied using bone-derived primary cell cultures. Both forms of FGF were relatively more mitogenic for bone cell populations with fewer osteoblastic (Ob) characteristics than for Ob-enriched cultures. However, in the Ob cultures, bFGF was intrinsically 10-fold more stimulatory than aFGF, whereas heparin enhanced the mitotic response only to aFGF. An optimal dose of either aFGF or bFGF (100 ng/ml) decreased alkaline phosphatase activity and increased the rate of noncollagen and collagen protein synthesis in Ob cultures. The stimulatory effect was relatively greater on noncollagen than on collagen synthesis, which resulted in a decrease in percent collagen synthesis. Neither factor altered the rate of collagen degradation. Furthermore, hydroxyurea diminished, but did not prevent, the stimulatory effect of each factor on rates of protein synthesis. In contrast, polyacrylamide gel analysis of newly synthesized protein and Northern blot analysis of steady state alpha 1 type I procollagen mRNA indicated differential effects by each agent on procollagen synthesis and processing. These studies suggest that the FGFs may produce their effects on Ob cells through both shared and disparate mechanisms, with the net result being a decrease in the expression of the osteoblastic phenotype. .A McCarthy TL; Centrella M; Canalis E. .I 201009 .U 90005155 .S Endocrinology 9001; 125(4):2134-40 .M Adenosine Cyclic Monophosphate/BI; Animal; Cells, Cultured; Dose-Response Relationship, Drug; Forskolin/PD; Gonadotropins, Chorionic/PD; Inhibin/*PD; Leydig Cells/DE/ME/*PH; Male; Pregnenolone/ME; Progesterone/ME; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Testosterone/AI/BI/ME; 8-Bromo Cyclic Adenosine Monophosphate/PD. .T Regulation of Leydig cell function in primary culture by inhibin and activin. .P JOURNAL ARTICLE. .W Inhibin and activin are gonadal glycoproteins that selectively inhibit and stimulate FSH release, respectively. Previously we have reported that transforming growth factor-beta inhibited hCG-stimulated testosterone formation in mature Leydig cells. In the present study we evaluated the effects of other members of the transforming growth factor-beta family, inhibin and activin, on Leydig cell function. We found that activin (0.1-10 ng/ml) had no effect on basal testosterone formation, but inhibited hCG-stimulated testosterone formation in a dose-dependent manner. Activin (10 ng/ml) inhibited hCG-stimulated testosterone formation by 42%. Activin also inhibited hCG-stimulated cAMP formation. In the presence of activin (5 ng/ml), forskolin (10 microM)- and 8-bromo-cAMP (0.1 mM)-induced testosterone formation were reduced about one third. Conversions of pregnenolone and progesterone to testosterone were also blocked by activin. Interestingly, [125I]hCG binding to Leydig cells and forskolin-induced cAMP formation were not affected by the addition of activin. In contrast to activin, inhibin (0.1-10 ng/ml) had no effect on hCG-induced testosterone formation at any concentration used. However, the inhibitory effects of activin on Leydig cell function were reversed by the concomitant addition of inhibin. Our results suggest that activin inhibits testosterone formation by the Leydig cells derived from normal mature rats. Multiple steps of the steroidogenic pathway are affected by testosterone. Inhibin alone has no effect, but reverses the inhibitory action of activin. .A Lin T; Calkins JK; Morris PL; Vale W; Bardin CW. .I 201010 .U 90005156 .S Endocrinology 9001; 125(4):2141-9 .M Animal; Cattle; Chromatography, Gel; Chromatography, High Pressure Liquid; Electrophoresis, Polyacrylamide Gel; Female; Follicular Fluid/*AN; Fractionation/MT; Inhibin/*; Molecular Weight; Protein Precursors/*IP; Radioimmunoassay; Support, Non-U.S. Gov't. .T Isolation of inhibin alpha-subunit precursor proteins from bovine follicular fluid. .P JOURNAL ARTICLE. .W Two proteins with structural characteristics similar to peptide sequences identified in the inhibin alpha-subunit precursor sequence have been isolated from bovine follicular fluid. A side-fraction from the purification of bovine follicular fluid inhibin with high levels of inhibin immunoactivity relative to its inhibin bioactivity was fractionated through a sequence of procedures which included triazine dye affinity and phenyl-Sepharose chromatography, gel permeation chromatography on Sephadex G-100, reverse phase HPLC, and preparative polyacrylamide gel electrophoresis. The first of the two proteins identified had a molecular mass of 25-26K under reducing and nonreducing conditions and a NH2-terminal sequence identical to that of 43K inhibin alpha-subunit and showed minimal activity (less than 2% activity) compared with bovine 31K inhibin in either the inhibin in vitro bioassay or the RIA. These data suggest that this protein is the alpha 1-166 sequence of the bovine inhibin alpha-subunit (designated alpha N-subunit), most likely released after processing of either the inhibin alpha-subunit precursor or the 43K alpha-subunit involved in the conversion of 58K to 31K inhibin. The other protein identified (designated pro-alpha C-subunit) has a molecular mass of 27K under nonreducing conditions and 20K and 6K under reducing conditions. It is inactive in the in vitro bioassay, although highly reactive in the inhibin RIA, and has NH2-termini identical to the pro sequence of the inhibin alpha-subunit precursor and the 20K alpha-subunit sequence. These results suggest that pro-alpha C is a disulfide-linked structure and may represent an intermediate in the dimerisation of alpha- and beta-subunits to form inhibin while the alpha N-subunit is probably a proteolytic product of either the alpha-subunit precursor or 58K inhibin. .A Robertson DM; Giacometti M; Foulds LM; Lahnstein J; Goss NH; Hearn MT; de Kretser DM. .I 201011 .U 90005157 .S Endocrinology 9001; 125(4):2150-7 .M Adenosine/AI/*PD/PH; Adenosine Cyclic Monophosphate/*ME; Adenosine Triphosphate/ME; Animal; Extracellular Space/ME; Guanosine Cyclic Monophosphate/*ME; Neural Transmission/*; Osmolar Concentration; Pineal Body/CY/*ME/PH; Rats; Support, U.S. Gov't, P.H.S.; Time Factors. .T Adenosine stimulates adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate accumulation in rat pinealocytes: evidence for a role for adenosine in pineal neurotransmission. .P JOURNAL ARTICLE. .W Adenosine produces a concentration-dependent increase in pinealocyte cAMP (EC50, approximately 0.3 nM) and cGMP accumulation (EC50, approximately 0.7 nM). Maximal increases in both nucleotides are evident 10 min after treatment; 1 h later values return to pretreatment levels. Concentration-dependent effects on cAMP are also observed with N6-(L-2-phenylisopropyl)adenosine (EC50, approximately 0.75 nM), 5'-N-ethylcarboxy aminoadenosine (EC50, approximately 0.75 nM), and 2-chloroadenosine (EC50, approximately 2.0 nM); the EC50 values for stimulation of cGMP with these agents are higher by a factor of 2-10. In the case of 5'-N-ethylcarboxy amidoadenosine, the concentration-response curve is biphasic, with a significant effect evident within the range of 1-100 pM. The stimulatory nature of this response and the relative potency of the agonists tested are consistent with the involvement of an A2-like adenosine receptor. Comparison of adenosine and the selective beta-adrenergic agonist isoproterenol indicated that their maximal EC50 values were generally similar. Studies with antagonists revealed that both 8-(p-sulfophenyl)theophylline (1 microM) and the xanthine amine congener (8-[4-[[[(2-aminoethyl)carbonyl]methyl]oxy]phenyl]1,3- dipropylxanthine (1 microM) inhibited the effects of adenosine (1 nM to 1 microM), but xanthine amine congener was more potent; the latter was markedly effective at 0.1 nM, whereas 8-(p-sulfophenyl)theophylline was nearly ineffective at this concentration. It was also determined that pineal cells generate extracellular adenosine from extracellular ATP. ATP is thought to be released along with catecholamines during neurotransmission. Hence, these studies support the view that adenosine could participate in the transsynaptic regulation of pineal function. .A Nikodijevic O; Klein DC. .I 201012 .U 90005158 .S Endocrinology 9001; 125(4):2158-66 .M Animal; Epidermal Growth Factor-Urogastrone/*ME; Female; Hypophysectomy; Liver/*ME; Male; Nucleic Acid Hybridization; Rats; Rats, Inbred Strains; Receptors, Epidermal Growth Factor-Urogastrone/*GE; RNA Probes; RNA, Messenger/*ME; Sex Characteristics; Somatotropin/*BL/PD; Support, Non-U.S. Gov't. .T Plasma growth hormone pattern regulates epidermal growth factor (EGF) receptor messenger ribonucleic acid levels and EGF binding in the rat liver. .P JOURNAL ARTICLE. .W It has recently been shown that GH increases the number of available hepatic receptors for epidermal growth factor (EGF). In the present study the effects of the sexually dimorphic plasma GH pattern (higher pulsatility in male rats) on hepatic EGF binding and EGF receptor mRNA concentration were investigated. The specific binding of [125I]EGF to purified liver membranes was about 2-fold higher in male rats than in females on days 35, 50, and 80 of life. EGF receptor mRNA levels, as determined by an RNase protection solution hybridization assay, were higher in males only on days 47-50. Hypophysectomy on day 50 reduced the EGF receptor mRNA concentration to a level that did not differ between male and female rats. In hypophysectomized rats of both sexes, intermittent GH treatment (sc injections every 12 h for 7 days) enhanced hepatic EGF receptor mRNA concentrations to normal male levels, while continuous GH administration was less effective. Northern blot analysis indicated that transcripts with apparent sizes of 9.5 and 6.6 kilobases were dependent on the plasma GH pattern. Intermittent iv GH replacement therapy for 5 days given at 3-h intervals by an automatic iv infusion system increased the hepatic EGF receptor mRNA concentration as well as specific EGF binding, whereas continuous iv GH infusion was ineffective. These results show that a pulsatile plasma GH pattern, similar to that of male rodents, is markedly more effective in enhancing hepatic EGF receptor mRNA levels and EGF binding than a continuous feminine GH pattern. These results are consistent with a pretranslatory stimulation of EGF receptor synthesis by pulsatile GH. .A Ekberg S; Carlsson L; Carlsson B; Billig H; Jansson JO. .I 201013 .U 90005160 .S Endocrinology 9001; 125(4):2175-86 .M Animal; Bile/*ME; Chromatography, High Pressure Liquid; Glucuronates/*ME; Propylthiouracil/*PD; Rats; Support, Non-U.S. Gov't; Thyroxine/BL/*ME; Triiodothyronine/ME. .T Effects of propylthiouracil on the biliary clearance of thyroxine (T4) in rats: decreased excretion of 3,5,3'-triiodothyronine glucuronide and increased excretion of 3,3',5'-triiodothyronine glucuronide and T4 sulfate. .P JOURNAL ARTICLE. .W The liver metabolizes T4 by deiodination and conjugation to T4 glucuronide (T4G), but little information exists about the formation of T4 sulfate (T4S) in vivo. We have examined the excretion of T4G, T4S, T3 and rT3 glucuronide (T3G and rT3G) in bile, collected under pentobarbital anesthesia 0-8 h or 17-18 h after iv [125I]T4 injection to control and 6-propyl-2-thiouracil (PTU)-treated rats. Radioactivity in bile, plasma, feces, and urine was analyzed by Sephadex LH-20 chromatography and HPLC. PTU induced a 2-fold increase in the biliary excretion of total radioactivity (26.6% vs. 15.0% dose between 0-8 h; 2.0% vs. 1.0% dose between 17-18 h). Biliary metabolites, 17-18 h after T4 injection, in control vs. PTU rats amounted to (percent dose): T4G, 0.44 vs. 0.75; T3G, 0.19 vs. 0.07; rT3G, 0.02 vs. 0.15; and T4S, 0.06 vs. 0.32. Similar results were obtained for control rats when bile was collected between 7-8 h after iv T4. The excretion rate of T3G was lower and that of rT3G higher when bile was continuously collected for 8 h immediately after T4 administration, probably due to prolonged experimental stress. However, regardless of the period of bile collection, PTU induced a more than 24-fold decrease in the T3G/rT3G ratio and a 5-fold increase in T4S excretion. In the animals killed 18 h after T4 injection, PTU treatment increased plasma T4 retention by 50%, reduced urinary I- excretion by 74%, and increased fecal radioactivity by 47%. No conjugates were detected in feces, and the distribution of fecal T4:T3:rT3 was 70:18:2 in control and 68:7:6 in PTU-treated rats. The results indicate that 1) the glucuronidative clearance of T4 is not affected by PTU; 2) the T3G/rT3G ratio in bile is a sensitive indicator of type I deiodinase inhibition; 3) T4 undergoes significant sulfation in rats in vivo, and 4) biliary excretion of T4S is enhanced if its type I deiodination is inhibited. .A Rutgers M; Pigmans IG; Bonthuis F; Docter R; Visser TJ. .I 201014 .U 90005161 .S Endocrinology 9001; 125(4):2187-97 .M Animal; Chromatography; Chromatography, High Pressure Liquid; Diiodothyronines/PD; Galactosamine/PD; Liver/CY/*ME; Microsomes, Liver/ME; Nitrophenols/PD; Osmolar Concentration; Pentachlorophenol/PD; Radioimmunoassay; Rats; Salicylamides/PD; Sulfates/PD; Support, Non-U.S. Gov't; Triiodothyronine/*ME/PD. .T Metabolism of triiodothyronine in rat hepatocytes. .P JOURNAL ARTICLE. .W The metabolism of T3 by isolated rat hepatocytes was analyzed by Sephadex LH-20 chromatography, HPLC, and RIA for T3 sulfate (T3S) and 3,3'-diiodothyronine (3,3'-T2). Type I iodothyronine deiodinase activity was inhibited with propylthiouracil (PTU), and phenol sulfotransferase activity by SO4(2-) depletion or with competitive substrates or inhibitors. Under normal conditions, labeled T3 glucuronide and I- were the main products of [3'-125I]T3 metabolism. Iodide production was decreased by inhibition (PTU) or saturation (greater than 100 nM T3) of type I deiodinase, which was accompanied by the accumulation of T3S and 3,3'-T2S. Inhibition of phenol sulfotransferase resulted in decreased iodide production, which was associated with an accumulation of 3,3'-T2 and 3,3'-T2 glucuronide, independent of PTU. Formation of 3,3'-T2 and its conjugates was only observed at T3 substrate concentrations below 10 nM. Thus, T3 is metabolized in rat liver cells by three quantitatively important pathways: glucuronidation, sulfation, and direct inner ring deiodination. Whereas T3 glucuronide is not further metabolized in the cultures, T3S is rapidly deiodinated by the type I enzyme. As confirmed by incubations with isolated rat liver microsomes, direct inner ring deiodination of T3 is largely mediated by a low Km, PTU-insensitive, type III-like iodothyronine deiodinase, and production of 3,3'-T2 is only observed if its rapid sulfation is prevented. .A Rooda SJ; Otten MH; van Loon MA; Kaptein E; Visser TJ. .I 201015 .U 90005164 .S Endocrinology 9001; 125(4):2212-4 .M Animal; Dose-Response Relationship, Drug; Gonadotropins, Chorionic/PD; Hamsters; Histamine/*PD; Light; Male; Mesocricetus; Periodicity; Progesterone/BI; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Testis/*ME; Testosterone/*BI. .T Histamine affects testicular steroid production in the golden hamster. .P JOURNAL ARTICLE. .W Localization of mast cells in the testis and ability of histamine (HA) to stimulate testicular testosterone (T) production in vitro were examined in gonadally active adult golden hamsters, kept under a long daily photoperiod (LD) and in gonadally regressed adult golden hamsters exposed to an inhibitory short photoperiod (SD). In both groups mast cells were present in the capsule of the testes and occasionally in vicinity of intratesticular blood vessels. Histamine stimulated T production in a dose dependent manner in incubations of regressed testes of SD animals, but had no stimulatory effect in the active testes of LD animals. In the incubations of SD testes, the effects of HA were abolished by the H-1 antagonist pyrilamine, but unaffected by the H-2 antagonist cimetidine. In both groups, HA enhanced the stimulatory effects of hCG. These results indicate that HA has steroidogenic activity in the testis and may be a factor involved in the regulation of Leydig cell function. .A Mayerhofer A; Bartke A; Amador AG; Began T. .I 201016 .U 90005165 .S Endocrinology 9001; 125(4):2215-7 .M Base Sequence/*; Binding, Competitive; Cell Line; Neoplasm Proteins/*GE; Parathyroid Hormones/*GE; Peptide Fragments/GE/*ME; Radioligand Assay; Receptors, Endogenous Substances/*ME; Sequence Homology, Nucleic Acid/*. .T Non-homologous sequences of parathyroid hormone and the parathyroid hormone related peptide bind to a common receptor on ROS 17/2.8 cells. .P JOURNAL ARTICLE. .W We and others have recently shown that amino terminal sequences of parathyroid hormone (PTH) and parathyroid hormone related peptide (PTHrP), which share a 62% homology within the first 13 residues, bind to the same receptor on ROS 17/2.8 cells. The remaining PTHrP sequence is markedly different from PTH, suggesting that receptor binding may be dependent on the first 13 amino acids of either peptide. However, since the amino acid residues 14-34 have previously been recognized as an important binding domain for PTH, conformational similarity within this portion's secondary structure of both peptides could contribute to their capacity to bind to the same receptor. To test this hypothesis, we synthesized [Tyr36,Cys38]PTHrP-(14-38) and [Tyr34]bPTH(14-34)NH2, and studied binding of both peptides to the common PTH/PTHrP receptor on ROS 17/2.8 cells. Radioiodinated, HPLC-purified [Nle8,18, Tyr34]bPTH(1-34)NH2 (NlePTH) and [Tyr36]PTHrP-(1-36)NH2 were used to functionally define receptor binding requirements. [Tyr36,Cys38]PTHrP(14-38) and [Tyr34]bPTH(14-34)NH2 competed with 125I-NlePTH for binding sites on ROS 17/2.8 cells with apparent Kds of 10 microM and 50 microM respectively. Both peptides also competed with 125I-[Tyr36]PTHrP(1-36)NH2 with apparent Kds of 30 microM and 10 microM respectively. In the same assay system, NlePTH and [Tyr36,Cys38]PTHrP(1-38)inhibited binding of either radioiodinated ligand with apparent Kds of 0.3 and 1.0 nM. These studies indicate that although [Tyr34]bPTH(14-34)NH2 and [Tyr36,Cys38]PTHrP(14-38) share virtually no sequence homology, their secondary structures must be sufficiently similar to permit binding to a common PTH/PTHrP receptor. .A Abou-Samra AB; Uneno S; Jueppner H; Keutmann H; Potts JT Jr; Segre GV; Nussbaum SR. .I 201017 .U 90005166 .S Endocrinology 9001; 125(4):2218-20 .M Animal; Cell Differentiation; Cell Nucleus/EN; Corpus Luteum/CY/*EN; DNA/ME; Electrophoresis, Agar Gel; Endodeoxyribonucleases/*ME; Female; Gonadotropins/BL/PD; Gonadotropins, Chorionic/PD; Granulosa Cells/*EN; Horses/BL; Pseudopregnancy/EN; Rats; Rats, Inbred Strains; Support, U.S. Gov't, P.H.S.. .T Developmental expression of Ca++/Mg++-dependent endonuclease activity in rat granulosa and luteal cells. .P JOURNAL ARTICLE. .W A Ca++/Mg++-sensitive endonuclease has been associated with programmed cell death in a variety of endocrine and non-endocrine dependent tissues. In view of the remarkable similarity of the process of the regression of the corpus luteum and other models of programmed cell death, we studied the occurrance of this endonuclease activity in granulosa cells at different developmental states and the corpus luteum. Our results show that while undifferentiated granulosa cells do not express this endonuclease activity, treatment with pregnant mares serum gonadotropin results in a rapid increase in endonuclease activity that is maintained following ovulation and luteinization of granulosa cells. .A Zeleznik AJ; Ihrig LL; Bassett SG. .I 201018 .U 90005167 .S Endocrinology 9001; 125(4):2221-3 .M Animal; Male; Nucleic Acid Hybridization; Pituitary Gland, Anterior/*ME; Rats; Rats, Inbred Strains; RNA, Messenger/*ME; Support, U.S. Gov't, P.H.S.; Thyroid Hormones/*PH; Thyrotropin/BL; Thyroxine/PD; Vasoactive Intestinal Peptide/*GE. .T Thyroid hormone regulates vasoactive intestinal peptide (VIP) mRNA levels in the rat anterior pituitary gland. .P JOURNAL ARTICLE. .W Vasoactive intestinal peptide (VIP) is a secretagogue for pituitary prolactin, but the importance of this peptide in the normal control of prolactin secretion is unclear. Recent studies suggest VIP synthesis within the rat anterior pituitary. We have shown (Endocrinology 124:1077) that the content of rat pituitary VIP increases in hypothyroidism. To confirm in situ pituitary synthesis of VIP and determine whether thyroid hormone effects on pituitary VIP relate to changes in VIP mRNA, Northern and in situ hybridization analyses of VIP mRNA in rat pituitaries were performed. Northern hybridization demonstrated an RNA species from rat pituitary consistent with rat VIP mRNA. Hypothyroidism increased the content of pituitary VIP mRNA, and replacement with 1-thyroxine prevented this increase. In situ hybridization showed multiple, widely-distributed hybridizing cells in pituitaries from hypothyroid animals. A distinct population of VIP-producing pituitary cells exists which may serve to modulate prolactin secretion in a paracrine or autocrine fashion. .A Segerson TP; Lam KS; Cacicedo L; Minamitani N; Fink JS; Lechan RM; Reichlin S. .I 201019 .U 90005168 .S Endocrinology 9001; 125(4):2224-6 .M Aldosterone/*ME; Animal; Binding Sites; Blood Vessels/EN/ME; Hydroxysteroid Dehydrogenases/ME; Male; Mineralocorticoids/ME; Rats; Rats, Inbred Strains; Receptors, Steroid/*ME; Splanchnic Circulation/*; Support, Non-U.S. Gov't. .T Vascular type I aldosterone binding sites are physiological mineralocorticoid receptors. .P JOURNAL ARTICLE. .W In vitro, Type I receptors have high and equivalent affinity for aldosterone, corticosterone and cortisol: in vivo, physiological mineralocorticoid target tissues (kidney, colon, parotid) are highly aldosterone-selective, in contrast with hippocampus and heart. In the present study we show that the mesenteric vascular arcade is similarly highly aldosterone-selective in vivo, and in vitro shows considerable levels of 11 beta OH steroid dehydrogenase activity, previously postulated as the mechanism whereby glucocorticoids are excluded from physiological mineralocorticoid receptors. .A Funder JW; Pearce PT; Smith R; Campbell J. .I 201020 .U 90005169 .S Endocrinology 9001; 125(4):2227-9 .M Aldosterone/BL/SE; Aldosterone Antagonists/*PD; Animal; Calcitonin Gene-Related Peptide/*PD; Cells, Cultured; Dogs; Female; Male; Osmolar Concentration; Rabbits; Support, Non-U.S. Gov't; Zona Glomerulosa/CY/SE. .T Calcitonin gene-related peptide is an inhibitor of aldosterone secretion. .P JOURNAL ARTICLE. .W This study examined the effects of calcitonin gene-related peptide (CGRP) on aldosterone secretion both in vivo and in vitro. Intravenous administration of CGRP (0.01 micrograms/kg) in 6 conscious dogs produced a significant decrease in plasma aldosterone concentration from 68 +/- 12 pg/ml to 28 +/- 11 pg/ml (p less than 0.05) despite a mild but significant elevation of plasma renin activity. In an in vitro study using isolated rabbit adrenal glomerulosa cells CGRP reduced the basal aldosterone secretion in a dose-related manner and furthermore 10(-9) M CGRP inhibited the aldosterone secretion stimulated by 10(-8) M angiotensin II. From these results it is suggested that CGRP has an inhibitory effect on aldosterone secretion. .A Murakami M; Suzuki H; Nakajima S; Nakamoto H; Kageyama Y; Saruta T. .I 201021 .U 90005172 .S Endocrinology 9001; 125(5):2253-7 .M Animal; Female; Litter Size; Mice; Placenta/AN; Placental Lactogen/AN/*BL; Pregnancy; Pregnancy, Animal/*BL; Radioimmunoassay/MT; Recombinant Proteins/AN; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Mouse placental lactogen-I: RIA and gestational profile in maternal serum. .P JOURNAL ARTICLE. .W A RIA for mouse placental lactogen-I (mPL-I) was developed using recombinant mPL-I as the standard, radioligand, and antigen for antiserum production. Displacement curves for dilutions of serum and placental extracts from pregnant mice were parallel to the recombinant mPL-I standard curve. Serum from male and nonpregnant female mice and high concentrations of mouse PRL, GH, PL-II, proliferin, and proliferin-related protein did not cross-react in the assay. mPL-I appeared in maternal serum on day 6 of pregnancy. Its concentration remained low until day 8 and them increased to a very large peak on days 9-11 (maximum concentration, approximately 8 micrograms/ml). The mPL-I concentration declined after day 11, but the hormone could be detected at low concentration in maternal serum until the end of pregnancy. On day 10 of pregnancy, the mPL-I concentration of maternal serum was correlated with litter size. Fractionation of serum from 10-day pregnant mice by size exclusion chromatography indicated the absence of high mol wt forms of mPL-I in the circulation. .A Ogren L; Southard JN; Colosi P; Linzer DI; Talamantes F. .I 201022 .U 90005173 .S Endocrinology 9001; 125(5):2258-66 .M Animal; Binding, Competitive; Cell Line; Cricetulus; Female; Hamsters; Intracellular Membranes/ME; Kinetics; Magnesium Chloride/PD; Mice; Microsomes/*ME; Microsomes, Liver/ME; Molecular Weight; Ovary/*ME; Placental Lactogen/*ME; Pregnancy; Receptors, Endogenous Substances/IP/*ME; Recombinant Proteins/ME; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Recombinant mouse placental lactogen-I binds to lactogen receptors in mouse liver and ovary: partial characterization of the ovarian receptor. .P JOURNAL ARTICLE. .W The binding of recombinant mouse placental lactogen-I (mPL-Ir) to liver and ovarian membranes was investigated in virgin and pregnant mice. Competitive binding assays demonstrated that mPL-Ir, mouse placental lactogen-II (mPL-II), and mouse PRL (mPRL) bind to the same receptors in ovarian membranes. The relative abilities of the three hormones to displace [125I]iodo-mPL-Ir from the ovarian lactogen receptors was mPL-II greater than mPL-Ir much greater than mPRL. Scatchard analysis of mPL-Ir binding to ovarian membranes from day 10 pregnant mice showed a Ka of 2.0 x 10(9) M-1 and a binding capacity of 3.2 x 10(-14) mol/mg membrane protein. The specific binding of [125I]iodo-mPL-Ir to ovarian membrane preparations was significantly higher on day 17 than on day 10 of gestation. Dissociation of endogenous hormones with 4 M MgCl2 increased the binding of [125I]iodo-mPL-Ir to ovarian membranes but not to liver membranes. Affinity cross-linking of [125I]iodo-mPL-Ir to liver and ovarian membranes resulted in the specific labeling of proteins with receptor mol wt (Mr) of 44K and 40K (nonreduced) and 50K and 42K (reduced), as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The lactogen receptors from liver and ovary appeared structurally homologous, producing fragments with similar Mr when treated with proteolytic enzymes and undergoing similar reductions in Mr when treated with glycolytic enzymes. The ability of mPLs to bind specifically and with high affinity to receptors in mouse ovarian membranes suggests that these hormones may regulate ovarian function during gestation. .A MacLeod KR; Smith WC; Ogren L; Talamantes F. .I 201023 .U 90005174 .S Endocrinology 9001; 125(5):2267-72 .M Carbohydrate Conformation; Carbohydrate Sequence; Carbohydrates/*AN; Chromatography, High Pressure Liquid; Female; Gonadotropins, Chorionic/*; Human; Molecular Sequence Data; Peptide Fragments/*; Pregnancy; Sialic Acids/AN. .T Carbohydrate composition of beta-core. .P JOURNAL ARTICLE. .W beta-Core is a major component of the hCG-related molecules found in pregnancy urine. We previously have purified the beta-core molecule and have deduced portions of its carbohydrate structure based on lectin binding data. In the present study we used recently developed technology to determine the carbohydrate composition of beta-core and hCG beta (CR119). For direct compositional analysis, parallel samples were hydrolyzed in trifluoroacetic acid and analyzed for sialic acid and neutral sugars without prior derivatization. Separation of the monosaccharides was achieved by HPLC on a Dionex CarboPac column eluted at high pH, and the resolved monosaccharides were quantified by pulsed amperometric detection. The amounts of sugar that were found relative to peptide indicated the presence of two N-linked oligosaccharides per molecule on both beta-core and hCG beta. hCG beta contained additional sugars consistent with the presence of four O-linked oligosaccharides. Compared to hCG beta, beta-core contained negligible sialic acid, galactose, or N-acetylgalactosamine. The compositional data suggest that beta-core does not contain N-acetylglucosamine at the nonreducing end of the molecule, whereas the trimannosyl-chitobiose core is apparently intact at both glycosylation sites, consistent with the ability of the molecule to bind to Concanavalin-A. Comparable fucose contents and abilities of beta-core and hCG beta to bind to Lens culinaris indicate a similar extent of fucosylation on the internal N-acetylglucosamine in both molecules. We propose that the N-linked oligosaccharides on beta-core closely resemble the underlying N-linked structures of hCG beta with the antennary sialic acid, galactose, and N-acetylglucosamine removed. .A Blithe DL; Wehmann RE; Nisula BC. .I 201024 .U 90005176 .S Endocrinology 9001; 125(5):2279-88 .M Adenosine Cyclic Monophosphate/PH; Amine Oxidoreductases/*BI/GE; Animal; Cell Line; Cells, Cultured; Cycloheximide/PD; Dexamethasone/PD; Dibutyryl Cyclic AMP/PD; Gene Expression Regulation/*/DE; Genes, Structural/DE; Heart Atrium/EN; Mice; Myocardium/EN; Organ Specificity; Pituitary Neoplasms; Rats; Rats, Inbred Strains; RNA/IP; RNA, Messenger/GE/IP; Support, U.S. Gov't, P.H.S.; Transcription, Genetic. .T Tissue-specific regulation of peptidyl-glycine alpha-amidating monooxygenase expression. .P JOURNAL ARTICLE. .W Peptidyl-glycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) is present in a variety of tissues, where it plays a vital role in the processing of numerous peptide substrates, often conferring bioactivity. PAM is present in high amounts in heart atrial myocytes and the pituitary gland, where activity is present in both soluble and membrane forms. We used AtT-20 cells, a mouse corticotrope tumor cell line, and primary heart atrial cultures to establish the occurrence of tissue-specific regulation of PAM expression. In the AtT-20 cells, PAM expression is regulated in parallel with the source of its peptide substrate, pro-ACTH/endorphin. PAM mRNA levels are increased to 132 +/- 5% of control values by treatment with (Bu)2-cAMP and decreased to 55 +/- 7% of control values by treatment with dexamethasone. Treatment with (Bu)2cAMP decreases PAM specific activity in the AtT-20 cells to 68 +/- 4% of the control value, presumably due to secretion of enzyme from the cells; dexamethasone treatment decreases PAM specific activity to 57 +/- 1% of the control value. In contrast, in heart atrial cultures, dexamethasone stimulates PAM expression. In atrial cultures exposed to dexamethasone for 48 h, PAM mRNA and PAM specific activity are elevated to 230 +/- 50% and 220 +/- 20% of control values, respectively; secretion of PAM activity is increased to 230% of the control value. As for AtT-20 cells, treatment of atrial cultures with (Bu)2cAMP increases PAM mRNA levels. Thus, PAM expression is regulated in a tissue-specific manner by dexamethasone in the two tissues examined. In AtT-20 cells, time-course studies and studies with cycloheximide indicate that dexamethasone exerts its effects on PAM mRNA levels by an indirect mechanism involving protein synthesis. .A Thiele EA; Marek KL; Eipper BA. .I 201025 .U 90005178 .S Endocrinology 9001; 125(5):2297-311 .M Androgens, Synthetic/ME; Animal; Binding, Competitive; Centrifugation, Density Gradient; Comparative Study; Cytosol/ME; Kinetics; Male; Microsomes/*ME; Nandrolone/AA/ME; Prostate/*ME; Rats; Rats, Inbred Strains; Receptors, Androgen/IP/*ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Relative binding properties of microsomal and cytosolic androgen receptor species of the ventral prostate. .P JOURNAL ARTICLE. .W A comparison between a microsomal and a cytosolic source of receptor-like androgen-binding activity was made in the rat ventral prostate. Microsomal binders remain in solution at 90% saturation with (NH4)2SO4 and display equal affinity for 5 alpha-dihydrotestosterone (DHT) and mibolerone. They have a half-life of dissociation of steroid-receptor complexes of 96 +/- 11 h and a 5S sedimentation coefficient for the untransformed moiety, with the appearance of a 3.5S species after incubation at 24 C for 30 min. They do not acquire DNA-binding capability after heat- or salt-attempted activation. Cytosol binders precipitate upon 90% saturation with (NH4)SO4 and have higher affinity for DHT than mibolerone. The half-life for dissociation of complexes is 85 +/- 14 h, and the complex sediments as an 8S moiety which is able to transform to a 4.4S form after heat activation correlated with increased DNA-binding ability of these species. Unactivated cytosol steroid-receptor complexes are also able to bind to DNA in the presence of molybdate. Salt-induced activation of cytosol moieties only occurred in the absence of molybdate. Microsomal androgen receptor is more stable than cytosol androgen receptor independently of the presence of hormone or partial purification of the moieties; the inactivation rates of the two forms of complexes differ 3-fold. Results indicate that androgen-binding sites associated with the microsomal and cytosolic fractions of the prostate are distinct entities. .A Steinsapir J; Bryhan M; Muldoon TG. .I 201026 .U 90005179 .S Endocrinology 9001; 125(5):2312-9 .M Alkaline Phosphatase/BL; Animal; Antlers/*GD; Bone Development/*; Calcifediol/*ME; Calcitriol/*BI/BL; Calcium/BL; Cells, Cultured; Deer; Horns/*GD; Male; Periodicity; Phosphates/BL; Seasons. .T Evidence for extrarenal production of 1,25-dihydroxyvitamin during physiological bone growth: in vivo and in vitro production by deer antler cells. .P JOURNAL ARTICLE. .W The development of deer antler follows a pattern similar to that described for mammalian endochondral ossification and has been proposed as a suitable model for studies of bone growth. We investigated seasonal changes in the plasma concentrations of 1,25-dihydroxyvitamin D [1,25-(OH)2D] and calcium and the activity of alkaline phosphatase in relation to the antler cycle during 1 yr in 4 captive roe deer and measured these biological parameters in 27 wild roe deer during their antler cycle. A significant elevation of 1,25-(OH)2D in peripheral plasma, with no parallel increase in the concentration of its precursor 25-hydroxyvitamin D, was observed to accompany the rapid growth phase of the antler cycle in captive (P less than 0.001) and wild (P less than 0.025) deer. During the same phase there was a gradient in levels of 1,25-(OH)2D in antler vs. jugular blood (P less than 0.01). In addition, velvet cells in culture proved to have the ability to convert 25-hydroxyvitamin D3 into a more polar derivative, which was indistinguishable from true 1,25-(OH)2D3 with regard to its chromatographic properties, its UV absorbance at 254 nm, and its ability to bind to the 1,25-(OH)2D3 receptors present in chick intestinal cytosol. These in vivo and in vitro results strongly suggest that local production of 1,25-(OH)2D by the antler cells does occur in vivo and may contribute to the increase in plasma 1,25-(OH)2D during bone growth. .A Sempere AJ; Grimberg R; Silve C; Tau C; Garabedian M. .I 201027 .U 90005180 .S Endocrinology 9001; 125(5):2320-7 .M Animal; Autoradiography; Brain/*EM/ME; Chick Embryo; Chickens; Insulin-Like Growth Factor I/*ME; Iodine Radioisotopes; Kinetics; Organ Specificity; Receptors, Endogenous Substances/*ME; Receptors, Insulin/*ME; Retina/EM/ME; Somatomedins/*ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Thermodynamics. .T Development of receptors for insulin and insulin-like growth factor-I in head and brain of chick embryos: autoradiographic localization. .P JOURNAL ARTICLE. .W In whole brain of chick embryos insulin receptors are highest at the end of embryonic development, while insulin-like growth factor-I (IGF-I) receptors dominate in the early stages. These studies provided evidence for developmental regulation of both types of receptors, but they did not provide information on possible differences between brain regions at each developmental stage or within one region at different embryonic ages. We have now localized the specific binding of [125I]insulin and [125I]IGF-I in sections of head and brain using autoradiography and computer-assisted densitometric analysis. Embryos have been studied from the latter part of organogenesis (days 6 and 12) through late development (day 18, i.e. 3 days before hatching), and the binding patterns have been compared with those in the adult brain. At all ages the binding of both ligands was to discrete anatomical regions. Interestingly, while in late embryos and adult brain the patterns of [125I]insulin and [125I] IGF-I binding were quite distinct, in young embryos both ligands showed very similar localization of binding. In young embryos the retina and lateral wall of the growing encephalic vesicles had the highest binding of both [125I]insulin and [125I]IGF-I. In older embryos, as in the adult brain, insulin binding was high in the paleostriatum augmentatum and molecular layer of the cerebellum, while IGF-I binding was prominent in the hippocampus and neostriatum. The mapping of receptors in a vertebrate embryo model from early prenatal development until adulthood predicts great overlap in any possible function of insulin and IGF-I in brain development, while it anticipates differential localized actions of the peptides in the mature brain. .A Bassas L; Girbau M; Lesniak MA; Roth J; de Pablo F. .I 201028 .U 90005182 .S Endocrinology 9001; 125(5):2335-40 .M Animal; Male; Neurons/DE/*PH; Nucleic Acid Hybridization; Orchiectomy; Rats; Rats, Inbred Strains; Reference Values; RNA, Messenger/*AN/GE; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Testosterone/BL/*PD; Thalamic Nuclei/DE/*PH; Vasopressins/*GE/PH. .T Steroid dependency of vasopressin neurons in the bed nucleus of the stria terminalis by in situ hybridization. .P JOURNAL ARTICLE. .W Recent immunocytochemical studies have suggested that vasopressin (VP) neurons in the bed nucleus of the stria terminalis (BNST) of the rat are gonadal steroid sensitive. In this paper we have used in situ hybridization and quantitative autoradiography to determine whether testosterone (T) and/or its metabolites modulate the biosynthetic capacity of VP neurons in the BNST of adult male rats. In Exp 1 the number of labeled cells and the average number of grains per cell were compared in sections sampled through the BNST of intact, castrated, and castrated male rats treated with physiological levels of T (1.6 +/- 0.1 ng/ml plasma). Castration dramatically reduced the number of labeled cells (P less than 0.01) and the intensity of labeling (P less than 0.05) of cells in the BNST. T, treatment of castrated animals reversed the effect of castration on both cell number and grains per cell. In Exp 2 treatment of castrated rats with supraphysiological levels of T (7.6 +/- 0.7 ng/ml plasma) increased the number of labeled BNST cells (P less than 0.05) and the intensity of labeling (P less than 0.05) over those in castrates treated with physiological levels of T or intact rats. These results indicate that T and/or its metabolites modulate expression of the VP gene by neurons in the BNST of adult male rats. .A Miller MA; Urban JH; Dorsa DM. .I 201029 .U 90005185 .S Endocrinology 9001; 125(5):2360-7 .M Adipose Tissue/*CY/ME; Animal; Cell Differentiation/*DE; Cells, Cultured; DNA/*BI/DE; Fibroblasts/CY/DE; Kinetics; Mice; Proteins/*BI; RNA/*BI/DE; RNA, Ribosomal/BI; Somatotropin/*PD; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Growth hormone-dependent events in the adipose differentiation of 3T3-F442A fibroblasts: modulation of macromolecular synthesis. .P JOURNAL ARTICLE. .W GH is necessary but not sufficient to induce adipose differentiation of 3T3-F442A fibroblasts in serum-free medium. Human (h) GH (2 nM) treatment of 3T3-F442A cells in serum-free medium caused a time-dependent (maximal at 48-72 h) and dose-dependent (EC50, approximately 0.2 nM) decrease (40-60%) in de nova protein synthesis. Insulin-like growth factor-I (IGF-I; 17 nM), PRL (2 nM), and glucagon (20 nM) did not decrease de novo protein synthesis, whereas bovine GH was equipotent with hGH. The half-lives of 35S-labeled proteins of 3T3-F442A cells were 21 and 57 h for cells maintained in serum-free medium for 3 days without or with hGH (2 nM), respectively. The total protein content of cells maintained in hGH (2 nM) for 1-4 days was unaffected compared to cells in serum-free medium alone. IGF-I (17 nM) treatment of cells for 4 days doubled the protein content of cells compared to control values in serum-free medium. hGH (2 nM) pretreatment of cells for 1-4 days had no effect on total RNA synthesis. hGH (2 nM) but not IGF-I (17 nM) treatment (3 days) resulted in a 7-fold decrease in cytoplasmic 18S rRNA content (as measured by DNA-RNA hybridization) of cells compared to that of control cells maintained in serum-free medium. When 3T3-F442A cells were transferred to serum-free medium there was a progressive decrease in DNA synthesis. The presence of hGH enhanced the rate at which DNA synthesis decreased for 3T3-F442A cells. IGF-I (17 nM) increased DNA synthesis by 6- and 8-fold after 2 and 3 days of IGF-I exposure. 3T3-F442A cells maintained in serum-free medium for 3 days responded to the addition of platelet-derived growth factor (2 U/ml) and insulin (1.6 microM) with a 56-fold increase in DNA synthesis, assayed 24 h later. 3T3-F442A cells treated with hGH (2 nM) for 3 days before platelet-derived growth factor and insulin addition exhibited a diminished DNA synthetic response, demonstrating that GH-exposed cells were partially refractory to mitogenic stimulation. GH had no effect on any aspect of macromolecular synthesis in 3T3-C2 cells, which have a low frequency of adipogenesis. Based upon these results a cell cycle model for the role of GH in the adipose differentiation of 3T3-F442A cells was proposed. .A Guller S; Sonenberg M; Wu KY; Szabo P; Corin RE. .I 201030 .U 90005187 .S Endocrinology 9001; 125(5):2375-84 .M Adenosine Cyclic Monophosphate/AA/*ME/PD; Adrenergic Alpha Receptor Agonists/*PD; Amino Acid Sequence; Animal; Cells, Cultured; Chickens; Forskolin/PD; Kinetics; Melatonin/*SE; Molecular Sequence Data; Pineal Body/DE/ME/*SE; Quinoxalines/*PD; Radioimmunoassay; Sequence Homology, Nucleic Acid; Structure-Activity Relationship; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Vasoactive Intestinal Peptide/*PD; 1-Methyl-3-Isobutylxanthine/PD; 8-Bromo Cyclic Adenosine Monophosphate/PD. .T Vasoactive intestinal polypeptide and alpha 2-adrenoceptor agonists regulate adenosine 3',5'-monophosphate accumulation and melatonin release in chick pineal cell cultures. .P JOURNAL ARTICLE. .W Vasoactive intestinal polypeptide (VIP) has been shown to stimulate melatonin synthesis in mammalian pineal; however, a regulatory role for VIP in the avian pineal has not been explored. Immunocytochemical and physiological response experiments were performed to investigate whether 1) immunoreactive VIP fibers innervated the avian pineal gland; 2) VIP had a specific effect on melatonin release that was mediated by cAMP stimulation; and 3) alpha 2-adrenergic signal transduction was associated with a reduction in cAMP levels. Immunocytochemical experiments demonstrated the presence of both tyrosine hydroxylase- and VIP-immunoreactive fibers in the avian pineal gland. Treatment of dispersed chick pineal cell cultures with VIP stimulated melatonin release (maximum 6-fold increase; EC50 = 1.8 nM) when administered during the 12-h light period of a 12-h light, 12-h dark cycle. Of the other four peptides tested [porcine VIP-(10-28), porcine peptide histidine isoleucine, porcine secretin, and human glucagon), only peptide histidine isoleucine stimulated melatonin release (EC50 = 30 nM). The effect of VIP was mediated by a time- and dose-dependent increase in cAMP accumulation (maximum 4-fold increase). The specific alpha 2-agonist UK-14,304 reduced cAMP accumulation (maximum 43% reduction) and inhibited melatonin release (EC50 = 19 nM) in the presence of 3 X 10(-8) M VIP. Norepinephrine-induced inhibition of nocturnal melatonin release was blocked by the elevation of cAMP achieved through the administration of forskolin (EC50 = 0.2 microM), isobutylmethylxanthine (EC50 = 112 microM), or 8-bromo-cAMP (EC50 = 166 microM). Collectively, these results demonstrate the presence and functional significance of VIP in the avian pineal gland, and the interaction of VIP and norepinephrine at the level of cAMP in the regulation of melatonin biosynthesis. .A Pratt BL; Takahashi JS. .I 201031 .U 90005188 .S Endocrinology 9001; 125(5):2385-91 .M Animal; Cell Line; Gene Expression/*DE; Genes, Structural/*DE; Insulin-Like Growth Factor I/*GE; Nucleic Acid Hybridization; Pituitary Neoplasms/*ME; Radioimmunoassay; Ribonucleases; RNA, Messenger/DE/GE; Somatomedins/*GE; Somatotropin/*PD; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Transcription, Genetic/DE; Translation, Genetic; Triiodothyronine/*PD. .T Pituitary insulin-like growth factor-I gene expression: regulation by triiodothyronine and growth hormone. .P JOURNAL ARTICLE. .W Most of the growth-promoting effects of GH are mediated through insulin-like growth factor-I (IGF-I). Pituitary GH gene expression is, in turn, inhibited by IGF-I. Since rat pituitary tissue and GH3 pituitary tumor cells express both the GH and the IGF-I genes, we have attempted to clarify their potential interactions in the somatotroph by examining hormonal factors involved in the regulation of pituitary IGF-I gene expression. IGF-I mRNA was measured in GH3 cells by a solution hybridization/RNase protection assay, using riboprobes to differentially protect the IGF-I variant mRNAs arising by alternative splicing at both the 5' untranslated (UT) and 3' ends of the primary transcript. GH3 cells contained both class A and class C 5' UT variant mRNAs, with a relative abundance similar to that found in the liver. Sixty-five percent of the total IGF-I mRNA in GH3 cells was processed at the 3' end to IGF-Ia, and 35% to IGF-Ib mRNAs, whereas in the liver the proportions were 85% and 15%, respectively. GH3 cells grown in thyroid hormone-depleted medium for 4 days contained low levels of IGF-I mRNA. T3 and human (h) GH induced total IGF-I mRNA content in thyroid hormone-depleted cells, with both 5' and 3' alternative transcripts regulated coordinately, an effect that was maximal at 48-72 h. T3 stimulation of GH3 IGF-I mRNA over 48 h was dose dependent (0.01-5 nM). Similarly, hGH (0.5-10 micrograms/ml) evoked a dose-dependent induction of IGF-I mRNA in the thyroid hormone-deficient GH3 cells. The effects of T3 (5 nM) and hGH (10 micrograms/ml) on IGF-I mRNA were not additive. Furthermore, the effects of both T3 and hGH were selective for IGF-I mRNA, as neither of these treatments stimulated PRL mRNA, and treatment with hGH decreased GH3 cell GH mRNA content. This model does not discriminate whether T3 has an independent effect on IGF-I gene expression or if its action is mediated solely through induction of GH. In conclusion, IGF-I mRNA transcripts are present in GH3 cells and are modulated by T3 and GH. Local paracrine or autocrine interactions may, therefore, be involved in the feedback control of GH secretion. .A Fagin JA; Fernandez-Mejia C; Melmed S. .I 201032 .U 90005191 .S Endocrinology 9001; 125(5):2407-13 .M Animal; Autoradiography; Cattle; Insulin-Like Growth Factor I/*ME; Insulin-Like Growth Factor II/*ME; Intracellular Membranes/ME; Iodine Radioisotopes; Male; Microsomes/ME; Molecular Weight; Rats; Rats, Inbred Strains; Receptors, Endogenous Substances/*AN/IP/ME; Retina/*ME; Somatomedins/*ME; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Localization and structural characterization of insulin-like growth factor receptors in mammalian retina. .P JOURNAL ARTICLE. .W Insulin-like growth factors (IGFs) are peptide mitogens, structurally related to insulin, whose biological actions in the CNS are incompletely known. The retina is largely uncharacterized with respect to IGF receptors. We, therefore, studied IGF receptors in bovine and murine retinal tissues by immunohistochemistry, autoradiographic localization, and affinity labeling. Notable IGF-II receptor immunoreactivity was found in retinal pigment epithelium (RPE), with intermediate levels in choroid, low levels in the inner and outer plexiform layers and outer nuclear layer, and very low levels in other regions. Autoradiographic localization using [125I]IGF-II confirmed the IGF-II receptor immunohistochemistry. Autoradiographic localization using [125I]IGF-I labeled the nuclear layers and the photoreceptor region. Affinity labeling disclosed differences in the apparent mol wt of IGF-I and IGF-II receptors from bovine eye tissues and those from liver and brain. IGF-I receptor alpha-subunits (the IGF-binding subunit) migrated at: liver, 139,000; brain, 125,000; RPE, 125,000 and 135,000 (two sizes); and retina, 125,000 and 135,000. IGF-II receptors migrated at: liver, 245,000; brain, 235,000; RPE, 240,000; and retina, 230,000. We conclude that mammalian retina contains both IGF-I and -II receptors, which differ from those found in other tissues and have a characteristic spatial distribution within the retina. .A Ocrant I; Valentino KL; King MG; Wimpy TH; Rosenfeld RG; Baskin DG. .I 201033 .U 90005192 .S Endocrinology 9001; 125(5):2414-20 .M Adenosine Cyclic Monophosphate/*BI; Animal; Cells, Cultured; Cholera Toxin/PD; Corpus Luteum/DE/*ME; Female; Forskolin/PD; Granulosa Cells/DE/*ME; Kinetics; LH/PD; Pertussis Toxins/PD; Protein Kinase C/*ME; Second Messenger Systems/*/DE; Support, U.S. Gov't, P.H.S.; Swine; Tetradecanoylphorbol Acetate/PD. .T Facilitative actions of the protein kinase-C effector system on hormonally stimulated adenosine 3',5'-monophosphate production by swine luteal cells. .P JOURNAL ARTICLE. .W The exact nature of the interaction(s) between cAMP and calcium-sensitive phospholipid-dependent protein kinase-C effector pathways is not well understood in many tissues, including the ovary. In the present work we have evaluated the ability of protein kinase-C to modulate receptor-and nonreceptor-mediated cAMP generation in acute suspension cultures of swine luteal cells. Cells were exposed to LH (1 micrograms/ml), forskolin (100 microM), cholera toxin (1 microgram/ml), pertussis toxin (100 ng/ml), and/or phorbol ester [12-O-tetradecanoylphorbol-13-acetate (TPA)] for 0-90 min. TPA had no effect on basal cAMP accumulation, but increased (P less than 0.05) LH-, forskolin-, and cholera toxin-activated cAMP formation, with maximal facilitation at 30, 45, and 60 min, respectively. This facilitative effect was robust, as it could be demonstrated in both the presence and absence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.5 mM). TPA increased dose-dependent LH (0.1-1 microgram/ml)-, forskolin (3-300 microM-, and cholera toxin (0.3-10 microgram/ml)-stimulated cAMP accumulation. TPA induced a dose-dependent (0.3-30 ng/ml) increase in cAMP accumulation when incubated with the half-maximally effective (ED50) and maximally effective doses of LH (0.8 and 1 microgram/ml, respectively), forskolin (10 and 300 microM), and cholera toxin (0.2 and 3 micrograms/ml). TPA had an ED50 for this functional activation of 6.1 (67% confidence interval, 4.4-9.7) nM. The stimulatory effect of TPA could be mimicked by two synthetic diacylglycerols, 1,2-Dioctanoylglycerol and 1-oleoyl-2-acetylglycerol, but not by inactive phorbol esters. In addition, TPA augmented the stimulatory effect of pertussis toxin when combined with maximally effective doses of LH, forskolin, and cholera toxin. The stimulatory action of TPA on cAMP production was limited to endogenous cellular adenylyl cyclase. Bacterially derived adenylyl cyclase toxin isolated from Bordetella pertussis resulted in a dose-dependent increase in cAMP formation over 60 min, which was not facilitated by phorbol ester. We conclude that stimulatory coupling exists between the calcium-dependent protein kinase-C and cAMP-generating systems in swine luteal cells. This stimulatory coupling is enacted in part at the levels of both the guanine binding and the catalytic subunits of adenylyl cyclase. .A Wheeler MB; Veldhuis JD. .I 201034 .U 90005193 .S Endocrinology 9001; 125(5):2421-33 .M Animal; Argipressin/PD; Calcium/*ME; Cells, Cultured; Diabetes Mellitus, Experimental/*ME; Epinephrine/*PD; Glucagon/PD; Glycogen Phosphorylase/ME; Inositol 1,4,5-Trisphosphate/ME/PD; Kinetics; Liver/DE/*ME; Male; Phentolamine/PD; Prazosin/ME; Rats; Rats, Inbred Strains; Receptors, Adrenergic, Alpha/DE/ME; Reference Values; Support, Non-U.S. Gov't. .T Effect of diabetes on hormone-stimulated and basal hepatocyte calcium metabolism. .P JOURNAL ARTICLE. .W The effects of diabetes on basal calcium metabolism and the response to endocrine stimulation were studied in hepatocytes from acute and long term diabetic rats. Hepatocyte calcium sequestration and turnover were increased in both acute and chronic diabetes. Cytosolic free calcium (Cai2+) was significantly increased in the chronic diabetics, but the rise in Cai2+ evoked by epinephrine, angiotensin, vasopressin, and glucagon was depressed. The blunted stimulation of phosphorylase-alpha activity in the diabetics was influenced by a 50-60% decrease in total cell activity of glycogen phosphorylase and the decreased rise in cytosolic free calcium. Insulin replacement corrected both basal and stimulated changes in the acute diabetes model. Depressed [3H]inositol trisphosphate formation in response to epinephrine or vasopressin and increased intracellular organelle calcium buffering were observed in hepatocytes from diabetic animals; both may effect the diminished rise in Cai2+. Several possible causes for the depressed rise in Cai2+ after stimulation in chronic diabetic animals were eliminated: 1) the number and affinity of alpha 1-adrenergic receptors for epinephrine were normal; 2) the initial rise in calcium influx evoked by epinephrine or vasopressin was not depressed; and 3) the ability of inositol trisphosphate to release calcium from intracellular organelles was not changed. The results suggest that the diabetic changes in calcium-mediated endocrine regulation of hepatic carbohydrate metabolism contribute to the general pathology of the disease. .A Studer RK; Ganas L. .I 201035 .U 90005194 .S Endocrinology 9001; 125(5):2434-8 .M Androstenes/*PD; Animal; Azasteroids/*PD; Male; Organ Specificity; Rats; Rats, Inbred Strains; Reference Values; Sex Maturation/*DE; Spermatogenesis/DE; Stanolone/*BL; Steroids, Heterocyclic/*PD; Support, U.S. Gov't, P.H.S.; Testis/DE/GD/*PH; Testosterone/BL/*SE; Testosterone 5-alpha-Reductase/*AI. .T The effect of a 5 alpha-reductase inhibitor on androgen physiology in the immature male rat. .P JOURNAL ARTICLE. .W To provide insight into the role of 5 alpha-dihydrotestosterone (DHT) in postnatal androgen physiology, we administered the 5 alpha-reductase inhibitor finasteride to male rats from birth through the onset of puberty. In 4-week-old control rats serum testosterone levels averaged 0.21 ng/ml, and DHT levels averaged 0.64 ng/ml. By 7 weeks of age, testosterone levels increased more than 7-fold to 1.57 ng/ml, while the circulating DHT level declined to 0.26 ng/ml. In both the 4- and 7-week-old inhibitor-treated animals, circulating DHT levels were 25-50% of control values, and circulating testosterone levels were higher than control values. In 7-week-old inhibitor-treated rats, the weights of prostate, penis, seminal vesicles, and epididymal tissues were only 30-50% those of the controls. However, DHT formation is apparently not critical for postnatal development of the preputial glands or the androgen-dependent perineal muscles, since the weights of these tissues were not affected by treatment with inhibitor. Treatment with the 5 alpha-reductase inhibitor had no apparent effect on testicular histology or daily sperm production despite the fact that testicular DHT content was lower (70%) and testosterone content was higher (250%) than those in controls. We conclude that DHT formation is important for the normal postnatal growth of the prostate, seminal vesicles, epididymis, and penis and may be important for normal feedback control of testosterone production in rats, but that its formation is not critical for the onset of spermatogenesis or the development of the preputial glands or the androgen-dependent perineal muscles. .A George FW; Johnson L; Wilson JD. .I 201036 .U 90005195 .S Endocrinology 9001; 125(5):2439-44 .M Animal; Brain Chemistry/*; Chromatography, Affinity/MT; Comparative Study; Concanavalin A; Electrophoresis, Polyacrylamide Gel; Hypophysectomy; Male; Molecular Weight; Organ Specificity; Peptide Mapping; Pituitary Gland/*AN; Prolactin/*AN/IP; Rats; Support, U.S. Gov't, P.H.S.. .T Comparison of brain and pituitary immunoreactive prolactin by peptide mapping and lectin affinity chromatography. .P JOURNAL ARTICLE. .W Immunoreactive PRL (IR-PRL) has been identified in many areas of the rat brain. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analyses we have recently shown that the primary IR-PRL protein in the rat brain has an apparent mol wt (Mr) of 24,000, which was identical to that of pituitary PRL. In these studies, brain and pituitary 24,000 Mr PRL were compared by peptide mapping and lectin chromatography. PRL-enriched fractions were prepared from the pituitary, hypothalamus, hippocampus, and pons-medulla and labeled with 125I. This material was further purified by immunoprecipitation, and immunopurified 24,000 Mr PRL was isolated by sodium dodecyl sulfate-gel electrophoresis. Cleavage of 125I-labeled 24,000 Mr IR-PRL prepared from the pituitary and the three brain regions with chymotrypsin resulted in identical peptide maps with two primary labeled peptide fragments (5,500 and 6,000 Mr), and approximately five less intense fragments. Similarly, trypsin cleavage of brain and pituitary 24,000 Mr IR-PRL resulted in the production of two major fragments (6,200, and 5,200 Mr), and three less intense fragments. Cleavage of the 24,000 Mr IR-PRL with Staphylococcus V8 protease resulted in identical fragment patterns with two primary peptide fragments (14,000 and 6,200 Mr). When the pituitary and brain 24,000 Mr PRL were applied to Concanavalin-A-Sepharose columns no 24,000 Mr PRL was absorbed. The similarity of the peptide fragments obtained from the cleavage of the 24,000 Mr IR-PRL from the brain and pituitary clearly indicate that the IR-PRL found in the brain has an amino acid sequence that shares a high degree of structural homology with pituitary PRL. .A DeVito WJ. .I 201037 .U 90005196 .S Endocrinology 9001; 125(5):2445-53 .M Adrenal Cortex/DE/SE; Adrenocorticotropic Hormone/BL/*SE; Animal; Arecoline/*PD; Cells, Cultured; Corticosterone/BL/*SE; Corticotropin-Releasing Hormone/PD/*SE; Hypothalamo-Hypophyseal System/*DE/PH; Hypothalamus/DE/SE; Male; Organ Culture; Pituitary Gland, Anterior/DE/SE; Pituitary-Adrenal System/*DE/PH; Rats; Rats, Inbred Strains; Reference Values. .T The muscarinic cholinergic agonist arecoline stimulates the rat hypothalamic-pituitary-adrenal axis through a centrally-mediated corticotropin-releasing hormone-dependent mechanism. .P JOURNAL ARTICLE. .W Several lines of experimental evidence suggest that acetylcholine and other cholinergic agonists are excitatory to the hypothalamic-pituitary-adrenal (HPA) axis. To examine the site on the HPA axis that is stimulated by cholinergic agents, we evaluated the in vivo and in vitro effects of the muscarinic cholinergic agonist arecoline in intact and pituitary stalk-transected rats as well as on isolated rat hypothalami, dispersed anterior pituicytes, and adrenocortical cells in culture. Arecoline, injected iv to catheterized, freely moving male Sprague-Dawley rats, stimulated plasma ACTH and corticosterone release in a dose-dependent fashion. The muscarinic cholinergic antagonist atropine significantly blunted the ACTH response to arecoline. Pituitary stalk transection led to diminished plasma ACTH and corticosterone responses to arecoline. Similarly, previous administration of anti-CRH serum significantly blunted these responses. These findings suggest that arecoline stimulates the HPA axis centrally, mainly via secretion of CRH. This hypothesis was confirmed by the dose-dependent ability of arecoline to cause hypothalamic CRH secretion in vitro, an effect antagonized by atropine, and its failure to elicit ACTH and corticosterone secretion by dispersed anterior pituicytes and adrenocortical cells in culture, respectively. These data suggest that the muscarinic cholinergic agonist arecoline stimulates the HPA axis in the rat and that this effect is mediated mainly by the release of endogenous CRH. Arecoline, therefore, appears to be a compound suitable to selectively evaluate the responsiveness of the central component of the HPA axis. .A Calogero AE; Kamilaris TC; Gomez MT; Johnson EO; Tartaglia ME; Gold PW; Chrousos GP. .I 201038 .U 90005198 .S Endocrinology 9001; 125(5):2463-9 .M Aldosterone/*SE; Angiotensin II/*PD; Animal; Calcium/*ME; Cattle; Cells, Cultured; Comparative Study; Cytosol/DE/ME; Kinetics; Nitrendipine/PD; Potassium/*PD; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Zona Glomerulosa/DE/ME/*SE. .T Evidence that angiotensin-II and potassium collaborate to increase cytosolic calcium and stimulate the secretion of aldosterone. .P JOURNAL ARTICLE. .W Angiotensin-II (AII) and potassium (K+) as stimuli of aldosterone secretion enhance each other's stimulatory potential. In the present study we looked for evidence that AII and K+ act through a common mechanism of signal transduction to affect secretion. Bovine adrenal glomerulosa cells were loaded with the calcium (Ca2+) probe aequorin to permit detection over prolonged time periods of the changes in cytosolic Ca2+ that occur in response to AII and K+. Perfusion fractions were collected for simultaneous measurement of aldosterone production rates. AII (10(-7) M) produced an immediate and transient increase in Ca2+, followed by a Ca2+ plateau that remained above baseline for as long as AII was present. An increase in K+ concentration (from 5 to 12 mM) produced a slow and eventually sustained increase in cytosolic Ca2+, which resembled the plateau produced by AII. Nitrendipine (10(-5) M) completely inhibited the secretory response to AII and K+ (during 60-min incubations) and inhibited the typical K+-induced increase in Ca2+. The sustained increase in Ca2+ with AII (the plateau) required extracellular Ca2+ and was proportional to the prevailing extracellular K+ concentration. When glomerulosa cells were incubated with AII, the aldosterone secretory response to K+ was substantially enhanced (P less than 0.001). In summary, stimulation by both AII and K+ resulted in a sustained increase in Ca2+ influx. AII-induced Ca2+ influx was dependent on the ambient K+ concentration. These results indicate that AII and K+ act together to determine the optimal rate of Ca2+ entry, which may then lead to the appropriate secretory rate of aldosterone. .A Pratt JH; Rothrock JK; Dominguez JH. .I 201039 .U 90005199 .S Endocrinology 9001; 125(5):2470-4 .M Adenyl Cyclase/*ME; Adenylyl Imidodiphosphate/PD; Animal; Cell Membrane/EN; Female; Graafian Follicle/*EN; Guanosine Triphosphate/ME/PD/*PH; Guanylyl Imidodiphosphate/PD; Kinetics; LH/*PD; Ribonucleotides/*PD; Support, U.S. Gov't, P.H.S.; Swine. .T Guanosine triphosphate fulfills a complete and specific nucleotide requirement for luteinizing hormone-induced desensitization of pig ovarian adenylyl cyclase. .P JOURNAL ARTICLE. .W Homologous desensitization of the ovarian LH-sensitive adenylyl cyclase in cell-free systems is known to be dependent on micromolar concentrations of GTP. In this study, we sought to determine whether the nucleotide requirement of GTP for desensitization is complete and specific. LH-dependent desensitization of the adenylyl cyclase of pig ovarian follicular membranes was examined without adding adenyl-5'-yl imidodiphosphate [AMP-P(NH)P] to prevent the degradation of nucleotide triphosphates. GTP at 0.1 mM or higher [in the absence of AMP-P(NH)P] was able to support the same amount of desensitization (30-35%) that occurs with 1 mM AMP-P(NH)P and micromolar concentrations of GTP. ATP, UTP, and CTP also supported maximal desensitization, but were 5-30 times less potent than GTP. The ED50 value for GTP (14 microM) was about 100 times higher than when the reaction was performed in the presence of 1 mM AMP-P(NH)P; the ED50 values for UTP (70 microM) and CTP and ATP (400 microM) were only 2-5 times higher than when AMP-P(NH)P was included. Incubation of [alpha-32P]GTP with pig follicular membranes demonstrated that 1 mM GTP was stable, whereas 10 microM or less was rapidly degraded unless 1 mM AMP-P(NH)P was included. The specificity of GTP for supporting desensitization was also demonstrated in experiments where guanyl-5'-yl imidodiphosphate, the nonhydrolyzable GTP analog, inhibited LH-induced desensitization which otherwise would have occurred in the presence of ATP, CTP, or UTP. These studies establish the complete and specific requirement of GTP for supporting desensitization of ovarian LH-responsive adenylyl cyclase. .A Ekstrom RC; Hunzicker-Dunn M. .I 201040 .U 90005200 .S Endocrinology 9001; 125(5):2475-85 .M Animal; Clonidine/*PD; Comparative Study; Feedback; Female; Immune Sera; Male; Ovariectomy; Rats; Rats, Inbred Strains; Reference Values; Sex Factors; Sex Maturation/*; Somatostatin/IM/PH; Somatotropin/BL/PD/*SE; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Sexually dimorphic characteristics of clonidine-induced growth hormone release and autofeedback. .P JOURNAL ARTICLE. .W The mechanism underlying the sexually dimorphic pattern of GH secretion in the rat has not been clearly elucidated. In this study differences in the regulation of GH secretion in males and females were analyzed by examining their sensitivity to alpha 2-adrenergic (alpha 2) stimulation and GH autofeedback. The model used in testing this system was the capacity of ovine (o) GH, injected into the third ventricle, to suppress the endogenous GH surge induced by clonidine (CLON), an alpha 2-agonist. In morning experiments, CLON (30 micrograms/kg BW, iv) was injected between 1000-1100 h in males. oGH (20 micrograms in 2 microliters vehicle) injected 3 h earlier inhibited the GH surge, which peaked 15 min after CLON injection in control animals receiving CLON alone. In females there was both no change in plasma GH levels and no difference between treatment groups in animals receiving 30, 50, 100, or 150 micrograms/kg CLON and saline controls. Preinjection of 20 micrograms oGH in proestrous or diestrous animals or 30 micrograms oGH in diestrous animals 3 h before CLON treatment did not depress plasma GH levels below those found in animals receiving CLON alone. Further, neither reducing the preinjection time to 2 h nor injecting 7, 13, or 20 micrograms oGH at this preinjection period suppressed basal or CLON-induced GH release. To facilitate comparisons in subsequent experiments the male protocol was followed. In evening experiments, CLON (injected between 2210-2240 h) stimulated a significant GH surge in diestrous females. However, preinjected oGH lowered basal GH levels but failed to suppress the CLON-induced GH surge. In somatostatin (SRIF) antiserum (anti-SRIF; 0.5 ml, iv)-treated adult diestrous animals, CLON induced a significant GH surge that was suppressed by oGH preinjection. In normal sheep serum-treated animals there was no significant response to either CLON alone or in combination with oGH. To determine the influence of ovarian hormones on GH release females were ovariectomized (OVXed) either pre- or postpubertally. After adult OVX, CLON induced an increase in GH release that was not suppressed by oGH pretreatment. In prepubertally OVXed animals CLON induced a substantial GH surge that was suppressed in animals preinjected with oGH. In prepubertally OVXed animals implanted with testosterone capsules the response to CLON and oGH was not significantly different from that after prepubertal OVX alone. Sham-operated animals responded to treatment in a manner similar to unoperated cycling females.(ABSTRACT TRUNCATED AT 400 WORDS) .A Conway S; Moherek R; Mauceri H; Richardson L. .I 201041 .U 90005201 .S Endocrinology 9001; 125(5):2486-93 .M Animal; Autoradiography; Female; Granulosa Cells/ME; Insulin-Like Growth Factor I/*ME; Iodine Radioisotopes; Kinetics; Ovary/*ME; Receptors, Endogenous Substances/AN/*ME; Recombinant Proteins/ME; Sheep; Somatomedins/*ME; Theca Cells/ME. .T Localization, characterization, and quantification of insulin-like growth factor-I-binding sites in the ewe ovary. .P JOURNAL ARTICLE. .W To assess a potential role of insulin-like growth factor-I (IGF-I) in the ewe ovary, the presence of IGF-I receptors and IGF-I-binding proteins was studied by binding assays performed on granulosa cell suspensions, in follicular fluid, and on ovarian sections. On the ovarian sections, labeling was quantified after autoradiography by microphotometry. Competition studies with IGF-I and insulin allowed us to estimate the relative proportions of binding proteins and type I receptors in the different compartments of the ewe ovary. Our results clearly show that saturable, specific, and high affinity IGF-I receptors are present on the ovine granulosa cells. At equilibrium for both granulosa cell suspensions and frozen sections, the Kd value was close to 2 nM. IGF-I binding proteins were also present in follicular fluid and stroma, thecal, and granulosa cells. At equilibrium for follicular fluid, the Kd value was 0.91 +/- 0.27 nM (mean +/- SE). Moreover, on frozen sections, it was shown that atresia of small follicles (less than 2 mm) was accompanied by a decrease in the number of IGF-I receptors and an increase in the number of IGF-I-binding proteins on granulosa cells. By contrast, this phenomenon was not observed in large follicles. These data indicate that granulosa cells of ewe ovary possess type I receptors, and IGF-I-binding proteins may modulate IGF-I action in the process of follicular growth and atresia. .A Monget P; Monniaux D; Durand P. .I 201042 .U 90005202 .S Endocrinology 9001; 125(5):2494-501 .M Amino Acid Sequence; Animal; Antibodies; Antigen-Antibody Complex/AN; Chickens; Comparative Study; Cytosol/ME; DNA/*ME; Female; Heat-Shock Proteins/*ME; Human; Molecular Sequence Data; Oviducts/ME; Peptide Fragments/IM/ME; Protein Binding; Rabbits; Rats; Receptors, Progesterone/IM/*ME; Sequence Homology, Nucleic Acid; Support, U.S. Gov't, P.H.S.. .T Antibodies to chicken progesterone receptor peptide 523-536 recognize a site exposed in receptor-deoxyribonucleic acid complexes but not in receptor-heat shock protein-90 complexes. .P JOURNAL ARTICLE. .W We have prepared monospecific polyclonal rabbit antibodies to the peptide sequence 523-536 of the chicken progesterone receptor. This region, located between the DNA-binding and hormone-binding domains, is predicted by hydropathic analyses to be on the surface of the protein. The synthetic peptide was coupled to keyhole limpet hemocyanin and injected into rabbits. Three rabbits produced antibodies; all three are specific for progesterone receptors, recognize both native and denatured receptor, and do not interfere with either hormone binding or receptor recognition of its DNA response element in gel retardation assays. However, the antibodies do not interact with cytosolic 8S receptor complexes which contain the heat shock protein hsp90, suggesting that this site is occluded in the 8S complex. In contrast, the antibodies recognize a type of receptor dimer which forms on the DNA response element. Thus, these antibodies are a unique tool for studying receptor protein-protein interactions. .A Weigel NL; Schrader WT; O'Malley BW. .I 201043 .U 90005203 .S Endocrinology 9001; 125(5):2502-9 .M Adenosine Cyclic Monophosphate/ME; Adrenergic Alpha Receptor Agonists/*PD; Adrenergic Beta Receptor Agonists/*PD; Alprenolol/PD; Animal; Brown Fat/DE/*EN/ME; Cells, Cultured; Dibutyryl Cyclic AMP/PD; Drug Synergism; Enzyme Activation; Forskolin/PD; Imidazoles/PD; Iodide Peroxidase/*ME; Isoproterenol/PD; Male; Norepinephrine/PD; Phenylephrine/PD; Prazosin/PD; Rats; Rats, Inbred Strains; Support, U.S. Gov't, P.H.S.; Yohimbine/PD. .T Alpha 1- and beta-adrenergic agents cause synergistic stimulation of the iodothyronine deiodinase in rat brown adipocytes. .P JOURNAL ARTICLE. .W Previous studies have shown that norepinephrine causes a marked increase in the iodothyronine 5'-deiodinase activity in dispersed brown adipocytes. This stimulation required mRNA and protein synthesis and was 3- to 4-fold greater in cells from hypothyroid than in those from euthyroid rats. To investigate the cause of this differential response, we incubated dispersed brown adipocytes with catecholamines, a specific alpha 1-agonist, forskolin, and (Bu)2cAMP alone and in combination. Our results show a synergistic effect of alpha 1- and beta-adrenergic catecholamines to increase the deiodinase, which leads to 2-fold (euthyroid) to 4-fold (hypothyroid) higher enzyme activities in the presence of both agonists than can be accounted for by additive effects of the two agents. Since alpha 1-agonists cause minimal stimulation alone, this response is due to an enhancement of the cAMP effect. The alpha 1 effect is mimicked by the calcium ionophore A23187, but not by phorbol ester alone. After 2-h exposure to beta-adrenergic agents or forskolin, hypothyroid cells had a reduced cAMP response, but alpha 1-agonists did not reverse this. These results demonstrate a complex interrelationship between alpha 1- and beta-adrenergic agonists and thyroid status in the regulation of deiodinase in the brown adipocyte. The increase in intracellular calcium due to an alpha 1-agonist markedly enhances the effects of cAMP on deiodinase activation, permitting a beta-adrenergic effect despite the impaired cAMP generation characteristic of hypothyroid adipocytes. This unexpected enhancement of the beta-adrenergic pathway in the hypothyroid state may be especially relevant for maintaining maximum T3 production, which is required for the normal thermogenic function of this tissue. .A Raasmaja A; Larsen PR. .I 201044 .U 90005208 .S Endocrinology 9001; 125(5):2540-9 .M Adrenocorticotropic Hormone/SE; Animal; Argipressin/PD; Cell Division; Cell Separation/MT; Cells, Cultured; Corticosterone/PD; Corticotropin-Releasing Hormone/PD; Culture Media; Kinetics; Male; Pituitary Gland/*CY/DE/SE; Pituitary Gland, Anterior/*CY/SE; Rats; Rats, Inbred Strains; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Growth and secretory responses of enriched populations of corticotropes. .P JOURNAL ARTICLE. .W The purpose of this study was to learn whether enriched populations of corticotropes could be grown without the other pituitary cell types. Corticotropes populations were enriched to 80-90% by counterflow centrifugation in an elutriator with the Sanderson chamber. After initial separation into small, medium, and large fractions, the cells were stimulated for 3 h with 0.5 nM corticotropin-releasing hormone (CRH) and then re-eluted to remove the enlarged corticotropes. More ACTH (6- to 10-fold) was released in media with 10% fetal bovine serum (FBS) than was released in media with no serum. The effects of FBS could not be mimicked by 0.3% BSA. Corticotropes grew in serum-containing media as long as they were plated at a density of at least 2500 cells per well. The corticotropes expanded in size and assumed two major morphological subtypes. Both stored ACTH and beta-endorphin. One subtype was flattened and pleomorphic. The other subtype was stellate with multiple processes. Cell counts showed a 2.5- to 3.8-fold increase in the number of labeled corticotropes during the first 21 days of culture. Then the numbers of cells declined rapidly. Basal secretion of ACTH rose 1.6-fold during the first week, plateaued after 14 days and then declined to less than 30% of first week levels. CRH stimulation produced dose-dependent increases in media ACTH. In 7 day cultures, both basal and stimulated levels of ACTH were similar to those in 7 day cultures of mixed pituitary cells (containing equivalent numbers of corticotropes). Stimulatory effects of CRH were evident for up to 42 days of culture. Arginine vasopressin enhanced CRH-mediated secretion in most cultures in the first week. Pretreatment with glucocorticoids (100 nM corticosterone) for 15 h blocked CRH-mediated secretion in all cultures. The studies showed that corticotropes do not need the other pituitary cell types for basic plating and basal and CRH-mediated secretory responses. Further tests of specific growth factors are needed to learn whether they will maintain function for longer periods. .A Childs GV; Lloyd J; Unabia G; Rougeau D. .I 201045 .U 90005212 .S Endocrinology 9001; 125(5):2573-9 .M Adrenal Glands/*AN/DE/SE; Aminoglutethimide/PD; Animal; Blood Proteins/*AN/PD/SE; Cattle; Cells, Cultured; Chromatography, High Pressure Liquid; Comparative Study; Digoxin/AN; Dogs; Erythrocyte Membrane/DE/ME; Ether, Ethyl/PD; Female; Human; Male; Ouabain/ME; Radioimmunoassay; Rats; Rats, Inbred Strains; Species Specificity; Support, Non-U.S. Gov't. .T An endogenous digitalis-like factor derived from the adrenal gland: studies of adrenal tissue from various sources. .P JOURNAL ARTICLE. .W We have previously reported that the adrenal gland is the probable origin of the digitalis-like immunoreactive material (DLI) present in the plasma of rats and other species which have never received cardiac glycoside drugs. The present study demonstrates that adrenal glands removed from rats and then chopped release an immunoreactive digitalis-like material into a serum-free minimal incubation medium. HPLC studies indicated that this immunoreactivity was not homogeneous. Since such material may be a mammalian steroidal ligand for the glycoside receptor on the sodium pump, we investigated whether release of this material could be inhibited by antagonizing the conversion of cholesterol to pregnenolone through the addition of aminoglutethimide (AG) to the incubation medium. Our observations indicate that this manipulation successfully inhibited pregnenolone production during both of our 2-h serial incubation periods. However, in neither incubation period was AG able to inhibit the release of DLI into the medium; rather, during the first 2-h period, the release of this material was increased in the presence of AG compared to that in controls. We attempted to determine whether DLI was of adrenocortical or medullary origin. Extracts of whole beef adrenal gland, beef cortex, whole rat adrenal gland, and whole dog adrenal gland diluted in parallel in RIA, suggesting that the assay detected the same or similar material in each tissue sample. Medullary and cortical tissue samples were dissected from slices of fresh beef adrenals and extracted for assay. These data indicated that the cortex was the primary source of endogenous digitalis-like material. Efforts to enhance release of this material from the cortex of intact rats was performed by exposing animals to ether stress. After ether stress, the plasma concentration of digitalis-like material was lower than that in controls. Finally, extracts of incubation medium from chopped adrenal glands indicate that this medium possesses the ability to inhibit the binding of radiolabeled ouabain to human erythrocytes, suggesting that adrenal glands release material that has the ability to be recognized by both antidigoxin antibodies and the ouabain-binding site of erythrocyte membrane Na+,K+-ATPase. .A Doris PA; Stocco DM. .I 201046 .U 90005213 .S Endocrinology 9001; 125(5):2580-6 .M Adrenal Cortex Neoplasms/*SE; Aminoglutethimide/PD; Animal; Blood Proteins/AN/PD/*SE; Cell Line; Digoxin/AN; Erythrocyte Membrane/DE/ME; Human; Kinetics; Mice; Ouabain/ME; Pregnenolone/SE; Radioimmunoassay; Support, Non-U.S. Gov't. .T An endogenous digitalis-factor derived from the adrenal gland: studies of adrenocortical tumor cells. .P JOURNAL ARTICLE. .W The present studies demonstrate that the murine adrenocortical tumor cell line Y-1 releases a digoxin-like immunoreactive material into both serum-supplemented nutrient medium and minimal Krebs-Ringer bicarbonate medium. Release of pregnenolone into minimal medium from these cells was consistently inhibited by addition of the cholesterol side-chain cleavage inhibitor aminoglutethimide. However, release of digoxin-like immunoreactivity (DLI) was not similarly affected. To exclude the possibility that DLI could be accounted for by cross-reaction with another known adrenal steroid, aminoglutethimide inhibition was accompanied by inhibition of 17 alpha-hydroxylase with SU-10603 and inhibition of 3 beta-hydroxysteroid dehydrogenase with cyanoketone. Once again, pregnenolone release was effectively inhibited, but no similar pattern of inhibition of DLI release was observed. Increasing the time of the incubation periods from 1 to 2 h did not change the pattern of secretion of pregnenolone or DLI. HPLC analysis of DLI released over prolonged culture periods into serum-supplemented nutrient medium showed high levels of DLI in a single major and several adjacent peaks. Analysis of the ability of extracts of Y-1-conditioned medium to compete with tritiated ouabain for binding to erythrocytes indicates that conditioned medium contained highly enriched levels of ouabain-like activity. On HPLC analysis, the distribution of this activity showed partial correlation with the distribution of DLI. These observations indicate that Y-1 cells produce and release significant quantities of a material with cardiac glycoside-like properties reflected in the cross-reactivity with antidigoxin antibodies and the ability to compete with ouabain for binding to erythrocytes. In substantiation of previous findings in chopped adrenal cultures, the cardiac glycoside-like activity does not appear to result from cholesterol side-chain cleavage or pregnenolone production, since inhibition of side-chain cleavage as well as subsequent 17 alpha-hydroxylation and 3 beta-dehydrogenation did not result in consistent inhibition of DLI release. .A Doris PA; Kilgore MW; Durham D; Alberts D; Stocco DM. .I 201047 .U 90005214 .S Endocrinology 9001; 125(5):2587-93 .M Animal; Cell Nucleus/ME; Cells, Cultured; Cytosol/EN; Female; Gene Expression/*; Genes, Structural/*; Intestine, Small/*EN; Isoenzymes/*GE; Kinetics; Lactation/*ME; Liver/*EN; Phosphoenolpyruvate Carboxykinases/BI/*GE; Pregnancy; Rats; Rats, Inbred Strains; RNA, Messenger/*GE; Support, Non-U.S. Gov't; Transcription, Genetic. .T Regulation of expression of the messenger ribonucleic acid encoding the cytosolic form of phosphoenolpyruvate carboxykinase in liver and small intestine of lactating rats. .P JOURNAL ARTICLE. .W The content of P-enolpyruvate carboxykinase enzyme mRNA (mRNA(PEPCK)) in the liver and small intestine changes in a coordinate way at various stages of pregnancy, lactation, and weaning periods of rats. On the ninth day of lactation, the accumulation of mRNA(PEPCK) in the liver and small intestine was 82% and 152%, respectively, compared with that in starved control rats. After 18 h of induced weaning, both tissues presented residual levels of mRNA(PEPCK). However, after 60 h of induced weaning, the accumulation of mRNA(PEPCK) increased to 60% in the liver and 76% in the small intestine compared with that in starved control rats. Adrenalectomy and bromocriptine-induced hypoprolactinemia decreased the content of this mRNA in the liver of lactating rats, while diabetes increased it. PEPCK gene transcription, determined in isolated nuclei, was 2.4-fold higher in the liver of lactating rats than in hypoprolactinemic animals, but 3.7-fold lower than that in starved animals. These results suggest that the mRNA(PEPCK) accumulation observed in the liver of lactating rats must be due to an increase in both transcription rate and messenger stabilization. PRL added to primary culture of hepatocytes obtained from lactating rats caused a dose-dependent increase in the level of mRNA(PEPCK) and mRNAc-myc. Therefore, the high PEPCK activity reported during lactation is due to increased amounts of mRNA(PEPCK), which, in turn, is due to a coordinated response at transcriptional and posttranscriptional levels, where PRL seems to play an important role. .A Zabala MT; Garcia-Ruiz JP. .I 201048 .U 90005219 .S Endocrinology 9001; 125(5):2621-7 .M Aging/*BL; Animal; Animals, Newborn; Blotting, Western; Carrier Proteins/*ME; Electrophoresis, Polyacrylamide Gel; Insulin-Like Growth Factor I/*AN; Insulin-Like Growth Factor II/*AN; Molecular Weight; Rats; Rats, Inbred Strains; Somatomedins/*AN; Support, U.S. Gov't, P.H.S.. .T Ontogeny of serum insulin-like growth factor binding proteins in the rat. .P JOURNAL ARTICLE. .W Insulin-like growth factors (IGF-I and -II) are peptide growth factors that may be important for neonatal development. Specific high affinity IGF binding proteins (BPs) have been characterized in serum and extracellular fluids. The major serum binding complex in the adult has an apparent Mr of 150 K, while the predominant BP in the neonate is approximately 30 K. In the rat, the transition from the neonatal BP to the adult form occurs during the third postnatal week, concomitant with an increase in serum IGF-I and a decrease in serum IGF-II concentrations. Using specific RIAs and Western ligand blot analyses we have characterized the changes in serum IGF and IGF BPs, respectively, during the early postnatal period. Seven BPs were identified in serum with apparent Mr values of 42, 41, 40, 38, 28, 26, and 22 K. After deglycosylation, the 42, 41, 40, and 38 K BPs were reduced to two bands with apparent Mr values of 35 and 32 K, while the 28, 26, and 22 K BP were unchanged. In the neonate, the 28, 26, and 22 K BPs were present, with the 28 K BP in highest concentration. With increasing age, the 28 K BP decreased and the 42, 41, 40, and 38 K BPs appeared at approximately 19 days of age. Comparison of Western ligand blots of neonatal serum, BRL-3A conditioned media, rat amniotic fluid, and rat cerebrospinal fluid (CSF) demonstrated that all contained a prominent 28 K BP. A polyclonal antibody (alpha Hec 1) developed against the 31 K human IGF-BP (hBP-31) immunoprecipitated the 28 K BP from neonatal rat serum, BRL-3A media, rat amniotic fluid, and rat CSF, but did not react with adult rat serum. These findings suggest that, in the rat, the predominant neonatal serum BP is structurally and immunologically similar to the major BRL-3A, amniotic fluid, and CSF BPs, but distinct from the predominant adult serum BP. .A Donovan SM; Oh Y; Pham H; Rosenfeld RG. .I 201049 .U 90005220 .S Endocrinology 9001; 125(5):2628-35 .M Affinity Labels/*ME; Animal; Cells, Cultured; Fibroblasts/ME; Human; Kinetics; Leydig Cells/ME; Male; Organ Specificity; Rats; Receptors, Androgen/*AN/ME; Sertoli Cells/ME; Skin/ME; Stanolone/*AA/CS/ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Testis/CY/*ME. .T Analysis of the androgen receptor in isolated testicular cell types with a microassay that uses an affinity ligand. .P JOURNAL ARTICLE. .W A microassay for the androgen receptor was developed to investigate the cellular distribution of receptor in freshly isolated testicular cell types. The microassay uses an androgen affinity ligand, 17 beta-dihydrotestosterone bromoacetate. Binding of this ligand by the androgen receptor is rapid and irreversible, which permits the development of a highly sensitive assay. The androgen receptor microassay is completed within 4 h and detects receptor in as little as 0.5 micrograms cellular protein. There was no detectable binding of the affinity label by albumin or Sertoli cell-secreted proteins, including androgen-binding protein. Androgen receptor was found in cellular sonicates of human foreskin fibroblast, rat ventral prostate, rat kidney, and rat liver. Although the relative distribution of receptor was similar to that obtained using a traditional equilibrium binding assay, the levels of receptor were significantly higher using the microassay. The androgen receptor microassay was subsequently used to investigate the receptor in isolated testicular cell types. Androgen receptor was detected in freshly isolated peritubular myoid cells (80 fmol/micrograms DNA), Sertoli cells (88 fmol/micrograms DNA), and Leydig cells (35 fmol/micrograms DNA). No androgen receptor was detected in a mixed population of germ cells. Hormones were not found to influence androgen receptor levels in cultured peritubular cells or Sertoli cells. Electrophoretic analysis of androgen receptor radiolabeled with the affinity ligand demonstrates a single 52-kDa form of the receptor in peritubular cells, Sertoli cells, and Leydig cells. The size of the androgen receptor species detected in the rat testicular cell types was slightly smaller than the 56-kDa protein detected in a human fibroblast cell line. The current study demonstrates the utility of the microassay and affinity ligand to investigate androgen receptor biology. Data indicate that androgen receptors are present in several testicular cell types and suggest that the control of testicular function by androgens probably involves actions on multiple cell types. .A Anthony CT; Kovacs WJ; Skinner MK. .I 201050 .U 90005222 .S Endocrinology 9001; 125(5):2645-55 .M Amino Acid Sequence; Animal; Chromatography, High Pressure Liquid; Comparative Study; Female; Immune Sera; Molecular Sequence Data; Organ Specificity; Peptide Fragments/*AN; Peptide PHI/*AN; Protein Precursors/*AN; Radioimmunoassay; Rats; Sequence Homology, Nucleic Acid; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Swine; Vasoactive Intestinal Peptide/*AN. .T Variable distribution of three molecular forms of peptide histidine isoleucinamide in rat tissues: identification of the large molecular form as peptide histidine valine-(1-42). .P JOURNAL ARTICLE. .W We previously isolated three forms of peptide histidine isoleucinamide (PHI) from rat small intestine by chromatography on Fractogel. Rat PHI-(1-27)-NH2 and rat PHI-(1-27)-Gly were identified by microsequence analysis. In the present work the third larger form was purified to homogeneity, being detected by RIA in preliminary steps and by RRA in the last steps. This form could be recognized by a PHI antiserum and an antiserum raised against the synthetic rat PHI-(22-27) fragment C-terminally extended by the connecting peptide linking PHI to vasoactive intestinal peptide (VIP) in their common PHI/VIP precursor, as postulated by the reported cDNA analysis of rat brain mRNA. Sequence analysis and C-terminal hydrolysis by carboxypeptidase-Y identified this large form as peptide histidine valine-(1-42), i.e. rat PHI-(1-27) C-terminally extended by the totality of the connecting peptide except for the terminal dibasic residues. We also documented the coexistence of the three PHI forms in rat brain, rachidian bulb, pituitary, adrenal glands, uterine horns, and stomach. Tissue distribution was highly variable. The classical PHI-(1-27)-NH2 form was best represented in rachidian bulb and somewhat less so in brain and uterine horns. PHI-(1-27)-Gly, while being particularly abundant in the small intestine, was very poorly present in rachidian bulb and uterine horns. Peptide histidine valine-(1-42) was the major form in pituitary and adrenal glands and was also well expressed in uterine horns. The three forms coexisted equally in stomach. This uneven distribution suggests a tissue-specific posttranslational processing of rat prepro-PHI/VIP. .A Cauvin A; Vandermeers A; Vandermeers-Piret MC; Robberecht P; Christophe J. .I 201051 .U 90005223 .S Endocrinology 9001; 125(5):2656-63 .M Adenyl Cyclase/*ME; Breast Neoplasms; Calcitonin/PD/*PH; Cell Line; Dinitrophenols/PD; Down-Regulation (Physiology)/*/DE; Enzyme Activation; Female; Forskolin/PD; Human; Kinetics; Lung Neoplasms; Protein Kinase C/*PH; Receptors, Endogenous Substances/*PH; Support, Non-U.S. Gov't; Tetradecanoylphorbol Acetate/*PD; Tumor Cells, Cultured/DE/*PH. .T Protein kinase-C-induced down-regulation of calcitonin receptors and calcitonin-activated adenylate cyclase in T47D and BEN cells. .P JOURNAL ARTICLE. .W T47D human breast cancer cells and BEN human lung cancer cells were preincubated with the tumor-promoting phorbol ester phorbol 12-myristate 13-acetate (PMA). In both cell lines there was a decrease in the binding of 125I-labeled salmon calcitonin ([125I]sCT) which was dependent on the dose and time of exposure to PMA. The effect on binding comprised at least two components: the apparent affinity for binding of [125I]sCT was decreased by PMA, and the rate of internalization of bound [125I]sCT was increased more than 2-fold in the presence of PMA. By using dinitrophenol to inhibit cellular metabolic energy and, therefore, receptor internalization, the PMA effects on receptor affinity were dissociated from those on endocytosis. The effects on binding were reflected in a decreased stimulation by sCT of adenylate cyclase activity. This was specific for the calcitonin receptor system, since PMA had no effect on prostaglandin-E2-stimulated adenylate cyclase in the T47D cell. Protein kinase-C (PKC) was implicated in the inhibitory effects of PMA on both binding and adenylate cyclase activation, since inhibition was reduced by simultaneous incubation with the PKC inhibitors H7 and H8. These results suggest that PKC is capable of mediating down-regulation of the CT receptor, and this is most likely by phosphorylation of the receptor itself or an associated protein. .A Findlay DM; Michelangeli VP; Robinson PJ. .I 201052 .U 90005224 .S Endocrinology 9001; 125(5):2664-9 .M Adrenal Cortex/DE/PH; Adrenal Medulla/DE/*PH; Adrenocorticotropic Hormone/BL/SE; Amphetamines/*PD; Animal; Corticosterone/BL/SE; Epinephrine/BL; Hypothalamo-Hypophyseal System/*DE; Kinetics; Male; Naphthalenes/*PD; Norepinephrine/BL; Piperazines/*PD; Pituitary-Adrenal System/*DE; Rats; Rats, Inbred Strains; Reference Values; Serotonin/*PH; Sympathetic Nervous System/DE/*PH; Tetrahydronaphthalenes/*PD. .T Serotonin agonists cause parallel activation of the sympathoadrenomedullary system and the hypothalamo-pituitary-adrenocortical axis in conscious rats. .P JOURNAL ARTICLE. .W The effects of three potent serotonin (5-HT) agonists with different structures and 5-HT receptor binding profiles on sympathoadrenomedullary and hypothalamo-pituitary-adrenocortical axis functions were assessed in conscious, freely moving male Sprague-Dawley rats. The 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), the 5-HT1C agonist, m-chlorophenylpiperazine (m-CPP), and the 5-HT2/5-HT1C agonist, 1-(2,5-dimethoxy-4-iodophenyl)2-amino-propane (DOI), all produced marked dose-dependent increases in plasma epinephrine and ACTH concentrations. Both epinephrine and ACTH responses peaked at 10 min and showed strong positive correlations across all drugs and doses studied. Corticosterone increases showed a saturable response pattern and were close to the maximum level with a relatively small (approximately 2.5-fold) increase in plasma ACTH concentrations. Norepinephrine levels showed small dose-dependent increases after 8-OH-DPAT and m-CPP and decreases after DOI treatment. These results suggest that both the sympathoadrenomedullary system and the hypothalamo-pituitary-adrenocortical axis can be activated via 5-HT1 and 5-HT2 receptors and that these two systems may have common or similar regulatory mechanisms triggered by these stimuli. .A Bagdy G; Calogero AE; Murphy DL; Szemeredi K. .I 201053 .U 90005229 .S Endocrinology 9001; 125(5):2701-9 .M Aging; Animal; Cell Nucleus/ME; Cytosol/ME; Estradiol/*PD; Estrone/*AA; Female; Hydroxyestrones/*PD; Male; Orchiectomy; Ovariectomy; Pituitary Gland/DE/GD/*PH; Posture; Preoptic Area/DE/*PH; Rats; Rats, Inbred F344; Receptors, Estrogen/DE/*PH; Sex Behavior, Animal; Support, U.S. Gov't, P.H.S.. .T Differential effects of estradiol and 16 alpha-hydroxyestrone on pituitary and preoptic estrogen receptor regulation. .P JOURNAL ARTICLE. .W 16 alpha-Hydroxyestrone (16OHE1), an endogenous metabolite of estradiol (E2), binds to the estrogen receptor (ER) with low affinity, but is estrogenic in various bioassay systems. 16OHE1 binds covalently to the ER in vitro, exhibits prolonged estrogenic bioactivity in vivo, and has been implicated in several estrogen-dependent diseases. This study examined the effects of 13 days of continuous infusion of E2 or 16OHE1 on lordotic behavior, pituitary growth, and ER regulation in the cytosolic and nuclear fractions of the pituitary and preoptic area of both sexes. Finally, simultaneous pituitary nuclear exchange assays and enzyme immunoassays were performed to search for covalent 16OHE1-ER complexes in vivo. E2 induced lordosis and pituitary growth in both sexes, while 16OHE1 was only slightly less effective. While E2 treatment increased nuclear ER concentrations 2-fold vs. control values, it decreased both cytosolic and total (cytosolic plus nuclear) ER concentrations in pituitary and preoptic area by approximately 3-fold vs. control values in both sexes by exchange assay. In contrast, 16OHE1 did not decrease total pituitary ER concentrations and only minimally decreased total preoptic ER concentrations. Simultaneous exchange assay and immunoassay of pituitary nuclear extracts demonstrated proportionate increases in ER levels in female vs. male and in E2-treated vs. 16OHE1-treated rats. The ratios of (ER enzyme immunoassay divided by ER-exchange) for each rat were similar regardless of metabolite administration. The correlation of individual measurements implied that ER localized to the nuclear fraction by either E2 or 16OHE1 retained both exchangeability and immunoassayability to similar extents, but did not support the presence of 16OHE1-ER covalent complexes. The results of this study suggest that 16OHE1 has significant estrogenic bioactivity, as manifest by its effects on lordosis and pituitary growth, but, in contrast to E2, does not decrease pituitary ER concentrations and only minimally decreases preoptic ER concentrations. This property may be important in the proposed pathogenetic action of 16OHE1 in estrogen-dependent disease. .A Lustig RH; Mobbs CV; Bradlow HL; McEwen BS; Pfaff DW. .I 201054 .U 90005231 .S Endocrinology 9001; 125(5):2719-27 .M Acid Phosphatase/AN; Animal; Cell Communication/*; Cell Division/DE; Cell Line; Cells, Cultured; Chromosome Banding; DNA Replication/DE; Epithelium/CY/DE/PH; Fibroblasts/CY/DE/PH; Karyotyping; Male; Prostate/*CY/DE/PH; Rats; Receptors, Androgen/AN; Stanolone/*PD; Steroids/PD; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Interaction between prostatic fibroblast and epithelial cells in culture: role of androgen. .P JOURNAL ARTICLE. .W We have established and characterized two cell lines from the ventral prostate gland of normal Nb rats: NbE-1 (prostatic epithelial) and NbF-1 (prostatic fibroblast) cell lines. To identify the direct mitogenic action of dihydrotestosterone (DHT), we incubated these cell lines alone and together (in the presence and absence of cell contact) with various concentrations of DHT (0.1-10,000 ng/ml) for 24-72 h and assayed for the rate of DNA synthesis and the total number of cells in tissue culture at specified time periods. Results demonstrate that the primary target for DHT mitogenic action is the prostatic fibroblasts. DHT inhibited the growth of prostatic epithelial cells by themselves, but stimulated prostatic epithelial cell growth when the epithelial cells were cocultured with prostatic fibroblasts. Furthermore, the cell-conditioned medium obtained from either the fibroblast or the epithelial cells stimulated in an autocrine or a paracrine manner the growth of prostatic cells in culture. These results are consistent with the concept that DHT stimulates the growth of prostatic epithelial cells indirectly via its direct mitogenic action on the prostatic fibroblasts. Because epithelial cells are the cell type principally responsible for converting testosterone to DHT, and the fibroblasts respond to the mitogenic action of DHT, our results support the concept that tight metabolic cooperation exists between prostatic epithelial and fibroblast cells. These data are in agreement with previous in vivo studies in which we have demonstrated that androgen receptors in the mesenchyme are obligatory for androgen-induced prostate growth and development. .A Chang SM; Chung LW. .I 201055 .U 90005233 .S Endocrinology 9001; 125(5):2735-44 .M Animal; Dithiothreitol/PD; Iodide Peroxidase/*AI; Kidney/*EN; Kinetics; Ligands; Male; Microsomes/DE/*EN; Microsomes, Liver/DE/*EN; Organ Specificity; Propylthiouracil/*PD; Rats; Rats, Inbred Strains; Reference Values; Support, U.S. Gov't, P.H.S.; Thyroxine/PD. .T Ligand-induced inactivation of type I iodothyronine 5'-deiodinase: protection by propylthiouracil in vivo and reversibility in vitro. .P JOURNAL ARTICLE. .W The inactivation of the phenolic ring deiodinases by natural substrates and iodinated contrast agents such as iopanoic acid (IOP) is a principal mechanism regulating the peripheral metabolism of thyroid hormones. The present studies were designed to investigate the cellular and biochemical mechanisms mediating this effect on type I 5'-deiodinase (5'DI) in rat liver and kidney. We reasoned that if inactivation requires the direct interaction of ligand (e.g. IOP) with 5'DI, then this effect should be blocked by a prior injection of 6n-propyl-2-thiouracil (PTU), which binds to an essential sulfhydryl group at the enzyme's active site and inhibits catalytic cycling. Experiments were performed using liver and kidney microsomes prepared from male rats injected 2.5 or 6 h earlier with various combinations of PTU, IOP, and/or vehicle. In initial studies, conditions were defined whereby active 5'DI could be regenerated in vitro from PTU-injected animals. This involved the treatment of microsomes with 50 mM dithiothreitol, pH 7.0, before assay. After this reductive treatment, 5'DI activity in both liver and kidney microsomes from rats previously injected with PTU, or the combination of PTU followed 30 min later by IOP, was equivalent to that in vehicle-injected control animals, whereas activity was decreased 60% in microsomes from animals injected with only IOP. This demonstrates that PTU protects 5'DI against ligand-induced inactivation, suggesting that this process is initiated by substrate binding to the enzyme's active site. In other experiments, liver microsomes from IOP-injected animals were pretreated with 100 mM dithiothreitol, pH 9.0, then washed, and 5'DI activity was determined. Under these stringent reducing conditions, 5'DI activity was completely recovered in microsomes from rats injected with IOP 2.5 h earlier, but only partially recovered 6 h after the IOP injection. Thus, ligand-induced inactivation of 5'DI may involve initially a reversible oxidation of the enzyme, followed by its irreversible inactivation. .A St. Germain DL; Croteau W. .I 201056 .U 90005236 .S Endocrinology 9001; 125(5):2758-65 .M Adenosine/*PD; Adenosine Deaminase/PD; Animal; Cell Line; Cholera Toxin/PD; Dibutyryl Cyclic AMP/PD; Drug Synergism; DNA/*BI/DE; DNA Replication/*DE; Forskolin/PD; Insulin-Like Growth Factor I/*PD; Kinetics; Somatomedins/*PD; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Thymidine/ME; Thyroid Gland/DE/*ME; Thyrotropin/AI/*PD; 1-Methyl-3-Isobutylxanthine/PD. .T Adenosine has divergent effects on deoxyribonucleic acid synthesis in FRTL5 cells: inhibition of thyrotropin-stimulated and potentiation of insulin-like growth factor-I-stimulated thymidine incorporation. .P JOURNAL ARTICLE. .W Adenosine inhibits TSH-stimulated [3H]thymidine incorporation into DNA in FRTL5 thyroid follicular cells by both inhibiting cAMP generation and acting at a locus beyond adenylate cyclase. On the other hand, adenosine markedly potentiates DNA synthesis in FRTL5 stimulated by insulin-like growth factor-I (IGF-I). The mechanisms of this latter effect are unknown, but require the coincubation of adenosine and IGF-I and not mediated by an increase in intracellular cAMP concentration. Adenosine increases the maximal response of FRTL5 to [3H]thymidine incorporation stimulated by IGF-I and increases the sensitivity of FRTL5 to IGF-I. These effects of adenosine are reflected by an increase in nuclear labeling as well as by an increase in [3H]thymidine incorporation into DNA. Adenosine also plays a role as an autocrine growth factor in FRTL5, since adenosine deaminase increases the response of these cells to TSH. The effects of adenosine on both TSH- and IGF-I-stimulated DNA synthesis are shared by guanosine and inosine, although with different potencies for the various guanine nucleosides. Inosine potentiates IGF-I-stimulated DNA synthesis, but inhibits TSH-stimulated DNA synthesis only weakly. Adenosine interacts with multiple receptors and with multiple postreceptor pathways in FRTL5 to produce divergent effects on the control of cell replication by two growth factors (TSH and IGF-I) that act through different postreceptor pathways. .A Moses AC; Tramontano D; Veneziani BM; Frauman AG. .I 201057 .U 90005238 .S Endocrinology 9001; 125(5):2773-9 .M Animal; Cell Nucleus/DE/*ME; Eosinophils/DE/*PH; Estradiol/*PD; Estradiol Antagonists/PD; Female; Kinetics; Peroxidases/ME; Pertussis Toxins/*PD; Rats; Rats, Inbred Strains; Receptors, Estrogen/DE/*PH; Reference Values; Support, U.S. Gov't, P.H.S.; Uterus/DE/ME/*PH. .T Estradiol-stimulated increases in uterine eosinophils and nuclear type II estrogen-binding sites are prevented by pertussis toxin. .P JOURNAL ARTICLE. .W Previous studies from several laboratories have demonstrated that estradiol treatment resulted in an increase in nuclear type II binding sites. Our previous data suggest that this increase was due to the estradiol-stimulated influx of circulating eosinophils. Therefore, we suggested that the uterine nuclear type II estrogen-binding sites were not of uterine origin. In this report we present further evidence to support this hypothesis. Treatment of immature rats with estradiol resulted in the stimulation of several uterine parameters, namely wet weight, protein synthesis, eosinophil number, peroxidase activity, nuclear type II binding sites, and the synthesis and secretion of a 180-kDa protein. The coadministration of pertussigen had no effect on the estradiol-stimulated increase in wet weight, protein synthesis, or the synthesis and secretion of the 180-kDa protein. However, pertussigen did prevent the estradiol-stimulated increase in eosinophils, peroxidase activity, and nuclear type II binding sites, demonstrating a coordinated response. Since peroxidase activity is known to be contained int he eosinophil, these data are consistent with our earlier demonstration that the type II sites are of eosinophil origin. These data also support and extend our previous findings in neonatal animals that estradiol can stimulate a growth response without a corresponding increase in the nuclear type II binding sites. These results further indicate that the estradiol-stimulated increase in eosinophils does not appear to play a key role in the control of uterine growth. .A Lyttle CR; Teuscher C; Medlock KL; Sheehan DM. .I 201058 .U 90005239 .S Endocrinology 9001; 125(5):2780-3 .M Animal; Calcium/*BL; Human; Hypocalcemia/*BL/CI; Interleukin-1/*PD; Mice; Recombinant Proteins/PD; Reference Values; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Time Factors. .T Bolus injections of recombinant human interleukin-1 cause transient hypocalcemia in normal mice. .P JOURNAL ARTICLE. .W Single daily injections of recombinant human interleukin-1 alpha (IL-1 alpha) or interleukin-1 beta (IL-1 beta) were given for 1-3 days to normal mice, and blood ionized calcium concentrations were measured before and at various times after each injection. Mean blood calcium levels fell significantly in both groups of animals 3 h after the first IL-1 injections and returned to pretreatment values at 5 h. However, at 24 and 48 h mean values were significantly higher than those in saline-heated controls. Despite this progressive underlying increase in mean blood ionized calcium concentrations, blood calcium concentrations also fell significantly 3 h after the second and third IL-1 injections. The transient decrease in blood calcium was prevented by treatment with indomethacin and, thus, appears to be prostaglandin mediated. Hypocalcemia was not observed after single bolus injections of tumor necrosis factor-alpha or -beta (lymphotoxin). These findings suggest that IL-1 is a potential mediator of the hypocalcemia that occurs in up to 40% of patients with bacteremic sepsis and severe tissue injury and is associated with an increased mortality rate. .A Boyce BF; Yates AJ; Mundy GR. .I 201059 .U 90005240 .S Endocrinology 9001; 125(5):2784-6 .M Animal; Aromatase/*GE; Blotting, Southern; Cholesterol Desmolase/*GE; Chromosome Mapping/*; DNA/GE; Genes, Structural/*; Linkage (Genetics)/*; Mice; Mice, Inbred Strains; Support, U.S. Gov't, P.H.S.. .T The structural genes encoding P450scc and P450arom are closely linked on mouse chromosome 9. .P JOURNAL ARTICLE. .W The chromosomal location of the two genes that encode the cytochrome P450 enzymes, P450SCC (cholesterol side-chain cleavage) and P450arom (aromatase), was identified in the mouse. Genomic DNA from several progenitor strains of recombinant inbred (RI) strains of mice was tested with various restriction endonucleases for restriction fragment length variations. Variation in Bam HI fragment length was detected between A/J and C57BL/6J. Genomic DNA from 43 RI strains derived from A/J and C57BL/6J was analyzed in a similar manner. Complete concordance of the strain distribution pattern for P450SCC and that of P450arom was observed for 43 RI strains. The lack of recombination indicates that the structural genes encoding P450SCC and P450arom are closely linked. The strain distribution patterns of the P450SCC and P450arom genes were compared with other markers previously mapped in these RI lines. The results demonstrate that both P450SCC and P450arom are found on mouse chromosome 9. Of the other loci on mouse chromosome 9, P450SCC and P450arom are most closely linked to the gene encoding P1450. Among 31 RI strains for which the three loci were analyzed, only one example of discordance was found. Human P450SCC, P450arom and P1450 have been mapped to human chromosome 15. However, the distance between the human P450SCC gene and other loci has not been determined. The information presented in this report, along with other studies, indicate conservation between homologous human and mouse chromosomal regions and suggest that human P450SCC will be found to be closely linked with human P450arom. .A Youngblood GL; Nesbitt MN; Payne AH. .I 201060 .U 90005243 .S Endocrinology 9001; 125(5):2793-4 .M Animal; Insulin-Like Growth Factor I/AN/*PD; Male; Mice; Mice, Inbred Strains; Somatomedins/*PD; Starvation/*PP; Support, Non-U.S. Gov't; Weight Loss/*DE. .T Insulin-like growth factor-1 (IGF-1) in mice reduces weight loss during starvation. .P JOURNAL ARTICLE. .W Plasma concentrations of IGF-1 decrease markedly during starvation secondary to a reduction in somatotropic receptors in the liver. We investigated whether IGF-1 administration during starvation in mice inhibits the catabolic state normally observed. Plasma concentrations of IGF-1 in starved mice receiving IGF-1 therapy were similar to values from non-starved mice, whereas bGH treatment failed to increase plasma IGF-1 levels. The degree of weight loss during 36 hours of starvation was reduced (p less than 0.01) by frequent treatment with subcutaneous IGF-1 but not by bGH therapy. The effect was restricted to the period 28 to 36 hours after commencement of the fast. These results suggest that a fall in circulating IGF-1 may play a role in the metabolic adaptation during malnutrition. .A O'Sullivan U; Gluckman PD; Breier BH; Woodall S; Siddiqui RA; McCutcheon SN. .I 201061 .U 90005310 .S Epilepsia 9001; 30(5):524-6 .M Case Report; Diabetes Mellitus, Insulin-Dependent; Electroencephalography; Epilepsy, Temporal Lobe/*CO; Hallucinations/*ET; Human; Illusions/*ET; Male; Middle Age; Vision Disorders/*ET. .T Prolonged spontaneous complex visual hallucinations and illusions as ictal phenomena. .P JOURNAL ARTICLE. .W A patient without a previous history of seizures had a generalized tonic-clonic seizure followed by multiple complex visual hallucinations and illusions (CVHIs) lasting weeks. The patient reported a total of 19 different CVHIs. EEGs performed revealed rhythmic right temporal activity occurring only during the CVHIs. Treatment with antiepileptic drugs (AEDs) resolved the CVHIs and normalized the EEG. An attempt at discontinuation of one AED resulted in a resurgence of the CVHIs and EEG abnormality. .A Sowa MV; Pituck S. .I 201062 .U 90005311 .S Epilepsia 9001; 30(5):527-31 .M Adult; Case Report; Electroencephalography/MT; Epilepsy, Temporal Lobe/*PP; Female; Human; Leg/*PP; Monitoring, Physiologic; Movement; Temporal Lobe/PP; Videotape Recording. .T Bicycling movements as a manifestation of complex partial seizures of temporal lobe origin. .P JOURNAL ARTICLE. .W Alternating movements of the limbs during a seizure, especially bicycling movements of the legs, are often taken as strong evidence for the psychogenic origin of seizure activity in an adult population. A recent review of pseudoseizure manifestations concluded that alternating limb movements were "highly characteristic of pseudoseizures." We report two adult patients with complex partial seizures of temporal lobe origin, confirmed by ictal video EEG recording, in whom bicycling movements were the prominent ictal manifestation. Bicycling occurred 5-30 s after ictal onset and lasted 15-30 s. Use of video EEG recording continues to increase our understanding of the wide range of behaviors which may occur in the course of an epileptic seizure, particularly complex partial seizures. Few absolute clinical criteria remain to distinguish epileptic seizures from pseudoseizures. These two cases and one other reported case clearly remove bicycling movements from that category. .A Sussman NM; Jackel RA; Kaplan LR; Harner RN. .I 201063 .U 90005312 .S Epilepsia 9001; 30(5):532-9 .M Adult; Electrodes; Electrodes, Implanted; Electroencephalography/IS/*MT; Epilepsy, Temporal Lobe/*DI/PP/SU; Female; Follow-Up Studies; Human; Male; Sphenoid Bone; Temporal Bone; Temporal Lobe/SU; Videotape Recording. .T Can sharp waves localized at the sphenoidal electrode accurately identify a mesio-temporal epileptogenic focus? .P JOURNAL ARTICLE. .W In our patient population that had undergone antero-temporal lobectomy, we found 20 patients with a unilateral sphenoidal/antero-temporal interictal focus. All patients had normal computed tomography (CT) scans. Invasive recordings with subdural electrode arrays placed over and under the temporal lobe were used in every patient. We found that the scalp interictal focus predicted for all patients that both the interictal sharp waves and ictal onset would be mesiobasal/anterotemporal in location on the subdural arrays. Seventy-five percent of these patients had an excellent outcome with temporal lobectomy. .A Morris HH 3d; Kanner A; Luders H; Murphy D; Dinner DS; Wyllie E; Kotagal P. .I 201064 .U 90005313 .S Epilepsia 9001; 30(5):540-6 .M Adult; Aged; Brain Diseases/DI/RA; Electroencephalography; Epilepsy, Temporal Lobe/*DI/RA; Female; Frontal Lobe/PA; Human; Magnetic Resonance Imaging/*; Male; Middle Age; Parietal Lobe/PA; Sclerosis; Single-Blind Method; Temporal Lobe/*PA/RA; Tomography, X-Ray Computed. .T Focal cerebral lesions found by magnetic resonance imaging in cryptogenic nonrefractory temporal lobe epilepsy patients. .P JOURNAL ARTICLE. .W Brain magnetic resonance imaging (MRI) was studied in patients with mild-to-moderate temporal lobe epilepsy (TLE), well controlled by pharmacotherapy, and with normal computed tomographic (CT) scans. Magnetic resonance imaging abnormalities were found in 19 patients; of these, nine had abnormalities in temporomesial regions and four in temporobasal regions. Six patients had white matter MRI lesions of nonspecific significance. The temporomesial MRI lesions were compatible with sclerosis of Ammonis cornu. Patients with this MRI finding had more severe and longer lasting TLE than those without MRI abnormalities. The temporobasal lesions were interpreted as potentially developing brain lesions. Correlation between EEG and MRI findings was good. We conclude that MRI is more useful than CT for diagnosis of patients with mild-to-moderate TLE. .A Franceschi M; Triulzi F; Ferini-Strambi L; Giusti MC; Minicucci F; Fazio F; Smirne S; Del Maschio A. .I 201065 .U 90005315 .S Epilepsia 9001; 30(5):559-63 .M Adult; Amygdaloid Body/SU; Brain Neoplasms/CO/*SU; Case Report; Epilepsy, Temporal Lobe/CO/*SU; Hamartoma/CO/*SU; Hippocampus/SU; Human; Male; Temporal Lobe/*SU. .T Relief of seizures from a predominantly posterior temporal tumor with anterior temporal lobectomy. .P JOURNAL ARTICLE. .W We report the relief of intractable complex partial seizures in a patient with a posteromesial temporal lobe hamartoma after anterior temporal lobectomy, despite minimal tumor removal. We suggest that the key to successful treatment is the mainly medial, or limbic, location of the tumor, which apparently requires anterior limbic structures for full clinical expression of seizures. We conclude that excision anterior to a posterior temporal lesion can result in seizure relief and that a medial tumor location may be important for successful treatment. .A Sperling MR; Cahan LD; Brown WJ. .I 201066 .U 90005317 .S Epilepsia 9001; 30(5):569-72 .M Aphasia/*ET; Aphasia, Acquired/*ET; Brain Diseases/DI/PS; Case Report; Child; Cysticercosis/*CO/DI; Electroencephalography; Epilepsy/*ET; Human; Male; Subarachnoid Space; Syndrome; Temporal Lobe/*PS. .T Acquired epileptic aphasia (the Landau-Kleffner syndrome) due to neurocysticercosis. .P JOURNAL ARTICLE. .W A healthy 7-year-old boy developed a language disorder associated with clinical seizures and a paroxysmal EEG. Computed tomography and magnetic resonance imaging revealed a small cysticercus deep in the left Sylvian fissure. We postulate a cause and effect relationship between the parasitic cyst and the clinical manifestations supported by the strategic location of the cyst and the critical age at which this lesion developed. This case provides evidence that the syndrome of acquired epileptic aphasia may be explained in terms of an unilateral structural brain lesion. .A Otero E; Cordova S; Diaz F; Garcia-Teruel I; Del Brutto OH. .I 201067 .U 90005318 .S Epilepsia 9001; 30(5):573-8 .M Amidohydrolases/BL; Autism/ET; Biotin/*TU; Brain Diseases/DT/*ET/ME; Case Report; Female; Human; Infant; Ketoglutaric Acids/UR; Myoclonus/ET; Spasms, Infantile/ET; Theta Rhythm. .T Biotin-responsive infantile encephalopathy: EEG-polygraphic study of a case. .P JOURNAL ARTICLE. .W A case of an infant suffering from progressive lethargy, sparse scalp hair, autistic-like behavior, myoclonias, and drug-resistant generalized seizures is reported. Laboratory investigations revealed, in the absence of metabolic acidosis, an increased urinary excretion of 2-ketoglutaric acid and a small peak of 3-hydroxyisovaleric acid. The serum biotinidase activity was 0.15 nmol min-1 ml-1 (normal range 5.2 +/- 0.9) in the propositus and 0.310 and 0.420 in her father and mother, respectively. The interictal EEG showed multifocal abnormalities; numerous seizures were recorded, with the pattern of true tonic-clonic fits, exceptional in infancy. Also myoclonias, auditory myoclonus, and repetitive startles were documented. Because of dramatic improvement of all symptoms and signs after starting biotin (5 mg twice daily), the authors suggest a therapeutical trial in all drug-resistant infantile seizures. .A Colamaria V; Burlina AB; Gaburro D; Pajno-Ferrara F; Saudubray JM; Merino RG; Dalla Bernardina B. .I 201068 .U 90005320 .S Epilepsia 9001; 30(5):582-9 .M Adolescence; Anticonvulsants/AD/*TU; Child; Child, Preschool; Electroencephalography; Epilepsy/CL/*DT/ET; Female; Follow-Up Studies; Human; Male; Multivariate Analysis; Probability; Prognosis; Prospective Studies; Recurrence; Risk Factors. .T Outcome after discontinuation of antiepileptic drug therapy in children with epilepsy. .P JOURNAL ARTICLE. .W We studied recurrence risks and predictive factors of relapse after antiepileptic drug (AED) discontinuation in a prospective analysis of 425 children with epilepsy who had not had a seizure for at least 2 years (follow-up after withdrawal 1.6-12 years, mean 8 years). Factors closely related by multivariate analysis to relapse were neurologic abnormalities, mental retardation, seizure type (infantile spasms, absence seizures), and appearance or persistence of EEG abnormalities during the course of the illness and before discontinuation. When multivariate analysis was performed to evaluate outcome of patients with a first relapse (isolated vs. multiple relapses), the variables closely related to a poor prognosis were etiologic factors, first relapse characterized by more than one seizure in a 24-h period, seizure-free period less than 4 years, unchanged seizure type at first relapse, more than one AED for seizure control, and abnormal EEG before the first relapse. In itself, resumption of therapy did not influence outcome. At the study cutoff point, 88% of patients with relapse were again seizure-free. We conclude that AEDs can safely be discontinued if predictive factors are considered to individualize the risk of relapse for each patient. .A Matricardi M; Brinciotti M; Benedetti P. .I 201069 .U 90005324 .S Epilepsia 9001; 30(5):607-10 .M Adrenocorticotropic Hormone/TU; Child Development; Electroencephalography; Human; Infant; Metharbital/TU; Methyltyrosines/AD/*TU; Methysergide/AD/*TU; Phenytoin/TU; Random Allocation; Recurrence; Spasms, Infantile/*DT/PP; Support, U.S. Gov't, P.H.S.; Tyrosine Hydroxylase/*AI. .T Treatment of infantile spasms with methysergide and alpha-methylparatyrosine. .P JOURNAL ARTICLE. .W Twenty-four newly diagnosed and previously untreated infantile spasm patients were treated for 3 weeks with either methysergide (12 patients) or alpha-methylparatyrosine (12 patients). Response to therapy was determined objectively with 24-h polygraphic/video monitoring techniques and was defined as cessation of spasms and disappearance of the hypsarrhythmic EEG pattern. Two (17%) of the patients treated with alpha-methylparatyrosine responded to therapy, and one (8%) of the methysergide-treated group showed a response. .A Hrachovy RA; Frost JD Jr; Glaze DG; Rose D. .I 201070 .U 90005328 .S Epilepsia 9001; 30(5):631-5 .M Animal; Anticonvulsants/*; Cats; Cerebellum/*PH; Cerebrospinal Fluid/AN/*PH; Electric Stimulation; Electroshock; Epilepsy/ET/*PC; Female; Injections, Intraventricular; Male; Pentylenetetrazole/AE; Peptides/AN/PD; Rats; Rats, Inbred Strains; Time Factors. .T Antiepileptic properties of cerebrospinal fluid after activation of the antiepileptic system of the brain. .P JOURNAL ARTICLE. .W Intraventricular injection of cerebrospinal fluid (CSF) obtained from cats with chronic electrical stimulation of cerebellar vermal cortex resulted in suppression of epileptic foci activity in cat brain cortex, an increase in time to first seizure, and weakening of generalized seizures in rats. The CSF obtained from cats after electroshock seizures induced less pronounced, although significant antiepileptic action in comparison with the CSF of cats with cerebellar stimulation on the model of generalized seizures in rats. The antiepileptic action of CSF obtained from cats with electrostimulation of cerebellar vermis and from electroshock cats is due to appearance of peptide factors in CSF. .A Kryzhanovsky GN; Shandra AA; Godlevsky LS; Karganov MY. .I 201071 .U 90005329 .S Epilepsia 9001; 30(5):636-739 .M Animal; Epilepsy/*; Human. .T AES proceedings. Annual meeting of the American Epilepsy Society. Boston, Massachusetts, December 3-6, 1989. Abstracts. .P JOURNAL ARTICLE. .I 201072 .U 90006418 .S Diabetes 9001; 38(10):1207-10 .M Aged; Analysis of Variance; Blood Glucose/AN; Body Weight/DE; Cholesterol/BL; Comparative Study; Deferoxamine/*TU; Diabetes Mellitus, Non-Insulin-Dependent/BL/*DT; Fasting; Female; Ferritin/*BL; Hemoglobin A, Glycosylated/AN; Human; Hypoglycemic Agents/TU; Male; Middle Age; Triglycerides/BL. .T Deferoxamine therapy in high-ferritin diabetes. .P JOURNAL ARTICLE. .W Serum ferritin and diabetes control were evaluated in 18 White patients with poorly controlled type II (non-insulin-dependent) diabetes who had no known causes of iron-storage disorder. Serum ferritin levels were found to be elevated with normal serum iron and total iron-binding capacity in 9 of the 18 patients studied. Because excess iron, typified by hemochromatosis, is associated with diabetes, and diabetes has been shown to improve after lowering total-body iron load through repeat venesection, I investigated whether regulating elevated ferritin levels could facilitate diabetes control. Deferoxamine (DFO), a known specific chelator of iron, was used because of its capacity to correct excess iron stores. All 9 patients in the high-ferritin diabetic group and 7 of 9 diabetic control subjects with normal serum ferritin levels were given DFO (10 mg/kg i.v.) twice weekly. Diabetic control, fasting glucose, triglyceride, cholesterol, HbA1c, and serum ferritin levels were monitored. Data show that lowering elevated ferritin levels correlated well with diabetes control and improved fasting glucose, triglyceride, and HbA1c in 8 of 9 patients with high ferritin levels. Lowering normal ferritin levels had no effect on diabetes control or on any of the other parameters in the 7 control subjects. This study shows there is a need to study iron metabolism in poorly controlled diabetes and demonstrates the value of DFO in controlling high-ferritin diabetes. .A Cutler P. .I 201073 .U 90006422 .S Diabetes 9001; 38(10):1231-7 .M Adult; Aged; Biological Markers/BL; Blood Pressure; Caucasoid Race/*; Colorado/EP; Comparative Study; Diabetes Mellitus, Non-Insulin-Dependent/*EH/PP; Diabetic Retinopathy/EH/*EP/ET; Hemoglobin A, Glycosylated/AN; Hispanic Americans/*; Human; Middle Age; Prevalence; Reference Values; Risk Factors; Support, U.S. Gov't, P.H.S.. .T Prevalence and risk factors of diabetic retinopathy in non-Hispanic whites and Hispanics with NIDDM. San Luis Valley Diabetes Study. .P JOURNAL ARTICLE. .W Diabetic retinopathy (DR) is the leading cause of blindness in adults in the United States. Because photocoagulation can reduce the incidence of blindness from severe DR by approximately 50%, it is important to identify people at increased risk for DR so that appropriate treatment can be accomplished. Use of populations at increased risk for diabetes may identify groups at increased risk for complications. A recent report from the San Antonio Heart Study showed that Mexican Americans were at greater risk for servere DR than non-Hispanic Whites. To compare the prevalence of DR between non-Hispanics and Hispanics in southern Colorado, 279 people with non-insulin-dependent diabetes mellitus (NIDDM) were identified, and retinal photographs identified the presence and severity of retinopathy. The worse eye was used to classify the severity of DR for each patient. Ninety percent of the subjects (166 Hispanics and 85 non-Hispanic Whites) were classified by retinopathy level. The duration-adjusted prevalence of any DR was 41.8% in Hispanics and 54.1% in non-Hispanic Whites. Severe DR (preproliferative and proliferative) occurred in 18.5% of the Hispanics and in 21.3% of the non-Hispanic Whites. The odds ratio for any DR, comparing Hispanics with non-Hispanic Whites adjusted for other risk factors, was 0.40 (95% confidence interval = 0.21, 0.76). Other risk factors for the presence of any retinopathy included use of exogenous insulin, increased duration of diabetes, younger age at diagnosis, increased glycosylated hemoglobin level, and increased systolic blood pressure. These data suggest that, compared with non-Hispanic Whites, Hispanics in Colorado may be at decreased risk for diabetic retinopathy. .A Hamman RF; Mayer EJ; Moo-Young GA; Hildebrandt W; Marshall JA; Baxter J. .I 201074 .U 90006424 .S Diabetes 9001; 38(10):1245-50 .M Capillaries/PA/PH/*PP; Diabetes Mellitus, Non-Insulin-Dependent/PA/*PP; Female; Human; Male; Mathematics; Middle Age; Models, Cardiovascular; Reference Values; Regression Analysis; Skin/*BS; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Relationships between microvascular function and capillary structure in diabetic and nondiabetic human skin. .P JOURNAL ARTICLE. .W Despite the commonly held view that abnormalities in capillary morphology, in particular thickening of the capillary basement membrane, are partly responsible for diabetic ischemia, few studies have correlated anatomic and hemodynamic variables in the same diabetic subjects. In a previous study of 24 type II (non-insulin-dependent) diabetic subjects and 24 age-matched control subjects, we showed that a standard finger exercise vasodilated cutaneous forearm vessels nearly equally (51%), but the postarteriolar flow responded differently between groups. Nondiabetic subjects increased flow by recruitment of capillaries, whereas diabetic subjects did so by capillary flow augmentation. Moreover, resting permeability-surface area product (PS) to pentetic acid was 85% higher in diabetic than nondiabetic subjects. In this study, these same subjects had their forearm skin biopsied and examined morphometrically by electron microscopy for capillary radius, basement membrane thickness, endothelial cell density, and a folding index of luminal membrane reduplication. All morphological variables were correlated stepwise in a saturated, analysis of covariance model with the physiological results. The correlations were sparse and specifically excluded basement membrane thickness. The highest r2 value was .432 between resting PS and a ratio of capillary density to endothelial cell number per capillary. These studies show little evidence that diabetic microvascular physiological variables are tightly connected to morphometric changes except for minor permeability changes, which rise with capillary density and decrease with endothelial cell number. Because PS to pentetic acid is increased in diabetic subjects at any level of capillary density, it seems reasonable that permeability may be increased above that of nondiabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS) .A Katz MA; McCuskey P; Beggs JL; Johnson PC; Gaines JA. .I 201075 .U 90006427 .S Diabetes 9001; 38(10):1271-4 .M Adolescence; Blood Glucose/AN; Comparative Study; Diabetes Mellitus, Insulin-Dependent/BL/*GE/IM; Family; Fasting; Female; Human; HLA Antigens/*AN; Male; Proinsulin/*BL; Reference Values. .T Elevated proinsulin in healthy siblings of IDDM patients independent of HLA identity. .P JOURNAL ARTICLE. .W Based on the recent demonstration of elevated serum proinsulin levels in cystic fibrosis patients with impaired glucose tolerance, it was hypothesized that proinsulin could be an indicator of altered beta-cell function. We therefore analyzed fasting proinsulin levels in 99 siblings of insulin-dependent diabetes mellitus (IDDM) patients, most of them discordant for diabetes for greater than 6 yr. The results from this group were compared with the results from 41 healthy age- and sex-matched control subjects with no family history of diabetes. Median (range) fasting proinsulin in siblings was 8.9 pM (1.7-58 pM) vs. 3.8 pM (less than 1.2-28 pM) in control subjects (P less than .00001). There was no difference between the groups in fasting blood glucose concentrations. Both groups had fasting insulin concentrations within the normal range with a tendency toward lower values in the siblings: 108 pM (60-237 pM) vs. 118 pM (71-175 pM) (P = .07). The 99 siblings were subdivided into groups according to HLA sharing with their diabetic proband. The concentration of proinsulin, insulin, and blood glucose among the groups of 33 HLA-identical, 40 HLA-haploidentical, and 26 nonidentical siblings did not differ significantly. The fasting proinsulin level did not correlate with fasting levels of insulin, blood glucose, age, or body weight. We conclude that fasting proinsulin is elevated in healthy siblings of IDDM patients, whereas fasting insulin is normal or slightly decreased independent of HLA identity with their diabetic sibling. Elevated proinsulin levels could represent a family trait, perhaps mirroring a beta-cell more vulnerable to destruction, or it could reflect previous beta-cell damage that does not lead to IDDM. .A Hartling SG; Lindgren F; Dahlqvist G; Persson B; Binder C. .I 201076 .U 90006429 .S Diabetes 9001; 38(10):1282-90 .M Abnormalities/*; Animal; Body Weight/DE; Diabetes Mellitus, Experimental/*PP; Diet; Female; Pregnancy; Pregnancy in Diabetes/*PP; Pregnancy, Animal/*DE; Rats; Rats, Inbred Strains; Reference Values; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Zinc/DF/ME/*PD. .T Influence of maternal dietary Zn intake on expression of diabetes-induced teratogenicity in rats. .P JOURNAL ARTICLE. .W Diabetic rat pregnancies are characterized by altered maternal and fetal Zn metabolism and a higher frequency of fetal malformations. In this study, the effect of varying maternal dietary Zn on pregnancy and fetal outcome and on maternal and fetal trace element status were investigated. Starting on day 0 of gestation, streptozocin-induced diabetic and nondiabetic control rats were fed a low-Zn diet (4.5 micrograms/g diet), an adequate-Zn diet (24.5 micrograms/g diet), or a high-Zn diet (500 micrograms/g diet) throughout gestation. Fetuses were taken by cesarean section on gestation day 20. Fetuses from diabetic dams were smaller, weighed less, and had less calcified skeletons and more malformations than fetuses from control dams. In the controls, maternal dietary Zn had a minor effect on fetal malformation frequency. In contrast, in the diabetic animals, the low-Zn diet had a strong teratogenic effect. In diabetic dams, the adequate- and high-Zn diets improved fetal length and weight more than it did in fetuses from nondiabetic dams. However, supplemental dietary Zn during diabetic pregnancy did not further improve malformation frequencies. Liver and kidney Zn, Cu, and metallothionein concentrations were higher in diabetic dams than in control dams. In contrast, liver Zn, Cu, and metallothionein concentrations in fetuses of diabetic dams were lower than in fetuses from control dams, regardless of maternal dietary Zn intake. These results show that diabetes during pregnancy can amplify the teratogenic effects of a mild maternal Zn deficiency.(ABSTRACT TRUNCATED AT 250 WORDS) .A Uriu-Hare JY; Stern JS; Keen CL. .I 201077 .U 90006431 .S Diabetes 9001; 38(10):1296-300 .M Alleles; Animal; Chromosome Mapping; Comparative Study; Diabetes Mellitus, Experimental/*PP; Diabetes Mellitus, Insulin-Dependent/*PP; Isoenzymes/AN; Kidney/EN; Leukocyte Culture Test, Mixed; Mice; Mice, Mutant Strains/*GE; Skin/BS; Skin Transplantation; Species Specificity; Support, Non-U.S. Gov't; Transplantation, Homologous. .T Comparison of high- and low-diabetes-incidence NOD mouse strains. .P JOURNAL ARTICLE. .W The nonobese diabetic (NOD) mouse is a model of insulin-dependent diabetes mellitus. These mice develop insulinopenia and hyperglycemia secondary to beta-cell destruction, which is associated with insulitis and autoantibody production. We have two strains of NOD mice: a low-incidence strain (NOD/Wehi), in which less than 10% females and less than 1% males develop diabetes by 150 days despite intense insulitis, and a high-incidence strain (NOD/Lt), in which most females and many males develop diabetes by 150 days. This phenotypic difference has been maintained for 24 mo despite identical housing in our specific pathogen-free unit. Reciprocal skin grafting and allozyme electrophoresis have not identified a difference between the strains. Mixed-lymphocyte cultures were performed with splenic T-lymphocytes cultured with equal numbers of irradiated stimulator splenocytes for 3-6 days. NOD/Wehi mice demonstrated a heightened syngeneic mixed-lymphocyte response (SMLR), averaging 19% of the allogeneic response to CBA/CaHWehi cells. The response to NOD/Lt stimulator cells was not significantly different from the syngeneic response. In contrast, NOD/Lt mice had an SMLR similar to that of BALB/cAnBradleyWehi control mice, averaging 5% of the allogeneic response. NOD/Lt cells also responded similarly to NOD/Wehi stimulator cells and briskly to allogeneic cells. The heightened SMLR in NOD/Wehi mice may reflect active generation of suppressor function, and this may account for the low incidence of diabetes. .A Baxter AG; Adams MA; Mandel TE. .I 201078 .U 90006487 .S Fam Med 9001; 21(5):325-6, 329 .M Advertising/*; Ethics, Medical/*; Family Practice; Human; Physicians/*. .T Physician advertising [letter; comment] .P COMMENT; LETTER. .A MacLean DS. .I 201079 .U 90006488 .S Fam Med 9001; 21(5):333-5 .M Family Practice/*; Female; Human; Obstetrics/*; Physician's Role; Physicians, Family/*; Pregnancy; Prenatal Care/*; Risk Factors; United States. .T Obstetrics and family practice: report of the expert panel on the content of prenatal care. .P JOURNAL ARTICLE. .A Culpepper L. .I 201080 .U 90006489 .S Fam Med 9001; 21(5):339, 341-2 .M Female; Human; Male; Physician's Role/*; Physicians, Family; Rape/PC; Role/*; Spouse Abuse/*PC; United States; Violence/*; Women. .T Violence against women: no more excuses. .P JOURNAL ARTICLE. .A Candib LM. .I 201081 .U 90006490 .S Fam Med 9001; 21(5):345-9 .M Diagnosis/*; Education, Medical; Human; Internship and Residency/*; Physicians, Family/*ED; United States. .T An enhancement of inpatient diagnosis clusters: applications to residency training. .P JOURNAL ARTICLE. .W The diagnosis cluster method has recently been used effectively to compare inpatient and outpatient clinical experiences across data sets for practicing physicians and family practice residents. This paper describes the use of the diagnosis cluster method to study the three-year experience of a class of family practice residents in one university program and three community hospital programs. A group of 10 additional clusters based on the criteria of frequency, clinical homogeneity, and educational importance were identified covering 14.3% of the diagnoses not falling within the established 52-cluster method. These residency-specific clusters require review and validation by further analysis of clinical data and peer review by faculty involved in residency education. .A Curtis P; Resnick J. .I 201082 .U 90006491 .S Fam Med 9001; 21(5):350-4 .M Career Mobility/*; Faculty, Medical/*SD; Human; Physicians, Family/*ED; United States. .T Testing a model of academic career development. .P JOURNAL ARTICLE. .W This study, based on a survey of current faculty members, confirms the previously proposed professional identity model of Knopke and Anderson. This model had predicted that personal and resident learner issues would be influential aspects of a faculty member's professional developmental needs and that during the initial years as a faculty member the influence of institutional issues would be less important. The study found that major concerns of new faculty members appeared to be: 1) acting as a role model; 2) developing teaching skills; and 3) maintaining clinical competency. New faculty were more likely to emphasize issues dealing with resident-faculty relationships if they came directly out of training programs than if they came out of practice settings. The study also demonstrated that the majority of family medicine faculty no longer came from private practice, and that a significant number now come directly from training programs. .A Swee DE; Winter RO; Hammond BL. .I 201083 .U 90006492 .S Fam Med 9001; 21(5):355-8 .M Career Mobility/*; Family Practice/*OG/TD; Forecasting; Human; Internship and Residency/*OG/TD; Medical Directors/*. .T Anticipating the future: a national survey of family practice residency directors. .P JOURNAL ARTICLE. .W The directors of family practice residencies were surveyed to measure the effect on family practice of the multitude of recent changes in medical organization and practice. The survey achieved a response rate of 80% (N = 306) and revealed that 90% of program directors were generally optimistic about the current status and future vigor of the specialty. Of the respondents, 72% expressed positive opinions regarding the effects of HMOs, and 93% perceived sufficient availability of practice opportunities. Due in large part to these perceptions, only 11% supported a proposal to combine family practice and internal medicine residencies. Teachers of family medicine are encouraged to pass along these measures of positive growth and optimism to medical students considering the specialty of family practice. .A Day TW; Hafferty FW. .I 201084 .U 90006493 .S Fam Med 9001; 21(5):359-63 .M Career Choice/*; Decision Making/*; Family Practice; Human; Specialties, Medical/*; Students, Medical/*; Support, Non-U.S. Gov't. .T Specialty career decision making of third-year medical students. .P JOURNAL ARTICLE. .W Medical Students who are deciding which specialty to enter sometimes do not choose the one they actually prefer. The purposes of this study were to compare specialty preferences of students with their choices, as well as to identify the factors on which decisions about entering family medicine are based. Of North Carolina's 429 third-year medical students, 59% responded in 1985 to a career preferences questionnaire that assessed the process of specialty decision making. Internal medicine was the most frequently chosen specialty when another was preferred. The frequency with which family practice was the career choice was affected little by differences between preferences and choices. Six factors were identified, with the curriculum as the major factor separating those who chose family practice from those who chose other primary care or non-primary care specialties. Based on these results, six suggestions are offered for medical school administrators and faculty desiring to increase the number of students selecting family practice. .A Nieman LZ; Holbert D; Bremer CC; Nieman LJ. .I 201085 .U 90006494 .S Fam Med 9001; 21(5):364-7 .M Clinical Competence/*; Comparative Study; Education, Medical/*; Educational Measurement/*; Human; United States. .T A comparison of the modified essay question and multiple choice question formats: their relationship to clinical performance. .P JOURNAL ARTICLE. .W The Department of Family Medicine at Jefferson Medical College has used the modified essay question as the final examination format for its required third-year clerkship since 1976. To compare the family medicine modified essay question format with the multiple choice question format used in the other five required junior clerkships, examination scores from 2,174 Jefferson graduates (1976-1985) were correlated with scores on the examinations of the National Board of Medical Examiners (NBME), ratings of clinical performance in the required third-year clerkships, and ratings on four global areas of postgraduate competence. Grades on the multiple choice examination in internal medicine consistently yielded the highest correlations with NBME scores and with postgraduate ratings of medical knowledge. Performance on the modified essay examination in family medicine had the lowest correlations in these areas. The family medicine scores, however, consistently yielded the highest correlations with overall third-year clinical performance and with postgraduate performance in the areas of data-gathering skills, clinical judgment, and professional attitudes. These results indicate that the modified essay question format may provide a different and important parameter in the evaluation of medical trainees. .A Rabinowitz HK; Hojat M. .I 201086 .U 90006495 .S Fam Med 9001; 21(5):368-73 .M Female; Health Services; Human; Physician's Role; Physicians, Family; Rape; Spouse Abuse/PX; Violence/*; Women/*. .T Violence against women as a health care issue. .P JOURNAL ARTICLE. .W Violence against women is prevalent and is understood to produce adverse physical and psychological consequences for its victims. Victimized women frequently visit family physicians seeking relief from their distress; yet violence against women has not been identified by medical professionals as a relevant concern. This paper discusses health issues of women who are victims of violence, and encourages family physicians, who are in a position to have a powerful effect on this social problem, to reframe this phenomenon as a pertinent issue. .A Burge SK. .I 201087 .U 90006496 .S Fam Med 9001; 21(5):374-8 .M Aptitude/*; Family Practice/*; Human; Interpersonal Relations; Research/*. .T Aptitude x treatment interactions in family medicine research. .P JOURNAL ARTICLE. .W A model for research, aptitude x treatment interactions (ATI), is presented. This model has some specific utility for family medicine research. ATI can test the interaction between individual differences (aptitudes) and experimental interventions (treatments). Thus, in an applied setting one might choose an intervention based on its suitability for a particular type of individual (as measured by some form of individual difference measure). Several studies confirm the usefulness of the approach, and examples are presented and discussed. Approaches to the study of ATI for the family medicine researcher are described with special attention to clinic based and patient education studies. .A Holloway RL; Rogers JC. .I 201088 .U 90006497 .S Fam Med 9001; 21(5):379-83 .M Human; Periodicals/*ST; Publishing/*ST; Writing/*ST. .T Medical writing and publication. .P JOURNAL ARTICLE. .W Medical writing and publication are important in developing the scholarly base of family medicine, as well as being integral to an academic career. The author must choose the best format for the topic-research report, review article, book chapter, or other. The five steps in writing for publication are: 1) conceptualization of the topic and how best to present data; 2) organization of material; 3) composition; 4) revision of drafts; and 5) manuscript preparation and submission. The author must overcome the impediments to scholarly activity, such as lack of time, and resolve to ascribe a high priority to medical writing and publication. .A Taylor RB. .I 201089 .U 90006498 .S Fam Med 9001; 21(5):384-6 .M Family Practice/*ED; Human; Internship and Residency/*; Male; United States; Vasectomy/*ED. .T A national survey of vasectomy training in family practice residency programs. .P JOURNAL ARTICLE. .W To investigate the prevalence of vasectomy training in family practice residencies, a national survey of program directors was undertaken, with a response rate of 93%. Of the respondents, 44% had specific residency programs to provide vasectomy training. Of the residencies with specific training programs, training was a requirement in 18%. A majority of programs with training (54%) had both lecture and surgery components, with the remainder having only surgery. In 45% of the programs with training, residents performed five or fewer vasectomies, and in only 22% of the programs did residents perform more than 10 vasectomies. Among the programs where training was elective, 63% of the residents took the training. Only one program reported a medicolegal problem, which resulted in an out-of-court settlement. .A Denniston GC; Eggertsen SC. .I 201090 .U 90006499 .S Fam Pract 9001; 6(3):165-7 .M Diagnosis/*; Education, Medical/*TD; Family Practice/*; Human; Referral and Consultation/*. .T The Edinburgh Declaration [editorial] .P EDITORIAL. .A Metcalfe DH. .I 201091 .U 90006500 .S Fam Pract 9001; 6(3):168-72 .M Confidentiality; Human; Motivation; Ontario; Peer Group; Personnel Management; Personnel Selection/*MT; Physicians, Family/*PX; Quality of Health Care; Random Allocation; Research Personnel/*PX; Support, Non-U.S. Gov't. .T Recruiting family physicians as participants in research. .P JOURNAL ARTICLE. .W Obtaining the voluntary participation of family physicians in quality of care research is a major problem in family practice research. An innovative approach was therefore required to recruit 120 randomly selected family physicians in southern Ontario in a quality of care study by the College of Family Physicians of Canada. A network of physician recruiters oriented to the study was organized for each district. This recruitment method resulted in an 84.5% participation rate. The relationship of these physician recruiters to the candidate and the method of approach were important factors in the enrolment process: the highest participation rate (95%) was obtained when the recruiters were friends of the candidate and when a personal meeting was arranged (91%). Recruiters were given an information package to help them in the recruitment process and rated the most useful items as follows: a policy statement about confidentiality, a description of the study and reprints of a published feasibility study. These results illustrate that cooperation in research in family physicians' offices can become a reality. .A Borgiel AE; Dunn EV; Lamont CT; MacDonald PJ; Evensen MK; Bass MJ; Spasoff RA; Williams JI. .I 201092 .U 90006501 .S Fam Pract 9001; 6(3):173-6 .M Choice Behavior; Female; Human; Male; Middle Age; Motivation/*; Physicians, Family/*PX; Primary Health Care/*; Research/*; Research Support/EC; Victoria. .T Factors affecting the level of interest and activity in primary care research among general practitioners. .P JOURNAL ARTICLE. .W This paper presents the results of a state-wide survey of general practitioners in Victoria, Australia. The survey assessed their level of interest in general practice research as well as factors influencing the decision to participate in research. The study was conducted during the formation of a general practice research network which was being linked to a new primary care research unit in the Department of Community Medicine at Monash University. Of the 3350 general practitioners surveyed 1116 responded. One third expressed a high degree of interest in general practice research. Previous research experience and barriers to general practice research were also studied. The areas in which the doctors felt most research was required were identified. The results are compared with another study of Canadian family physicians, which is the only study of a similar nature previously published. The implications of the results are discussed with reference to the future direction of research by general practitioners. .A Silagy CA; Carson NE. .I 201093 .U 90006502 .S Fam Pract 9001; 6(3):177-81 .M Adult; Family Practice/*ST; Female; Fetal Death/ET/*PC; Human; Israel; Medical Audit/*MT/ST; Medical Records/ST; Peer Review; Pregnancy; Rural Population. .T Methodological issues associated with an audit of stillbirth in a family medicine practice in Israel. .P JOURNAL ARTICLE. .W An audit of 'deficient outcome' involves the step-by-step analysis of every event preceding the occurrence of a preventable medical outcome in order to determine exactly what went wrong. This paper describes methodological problems and related issues associated with a deficient outcome audit undertaken on five stillbirths which occurred in a rural family medical practice in Israel between 1985 and 1987. Problems included initial official disinterest towards the audit, and the high levels of suspicion and antagonism which it aroused in hospital staff approached for information. The problematic aspect of such audits needs more attention. The importance of this type of audit for establishing the precise reasons for perinatal deaths, and thus for maintaining antenatal care standards is discussed. In view of the small numbers of such events likely to occur within any one family practice it is not only feasible but also desirable for more family doctors to carry out such audits routinely, despite the difficulties which are involved. .A Furst AL; Shamba E. .I 201094 .U 90006503 .S Fam Pract 9001; 6(3):182-7 .M Adaptation, Psychological/*; Ambulatory Care Facilities/*UT; Decision Making; Female; Health Status/*; Human; Israel; Male; Middle Age; Personality; Primary Health Care/*; Random Allocation; Sick Role. .T Personal and health factors associated with frequency of visits to the primary care clinic. .P JOURNAL ARTICLE. .W A random sample of 170 patients registered in two primary care clinics of the workers' sick fund in Beer Sheva was selected to investigate the impact of health factors and personal coping style on visits to the primary care physician. It was hypothesized that health state (presence or absence of long-term illness) would be directly related to the frequency of visits as well as indirectly related to frequency of visits through its impact on the number of transient symptoms reported and patterns of response to common symptoms such as headaches, fever, and body aches. It was hypothesized, also, that an individual's personal coping style (according to the degree of repression or sensitization to illness) would be indirectly related to visits in a similar manner. The hypotheses were supported for persons suffering from long-term illnesses. Among the people who did not have long-term illnesses, personal coping style as measured on the repression-sensitization scale was related to the number of symptoms reported and the pattern of response to common symptoms but neither of these were related to frequency of visits. .A Antonovsky H; Maoz B; Pilpel D; Arad T. .I 201095 .U 90006504 .S Fam Pract 9001; 6(3):188-92 .M Adult; Attitude to Health/*; Female; Human; Male; Patient Education; Physician-Patient Relations/*; Placebo Effect/*; Prognosis; Random Allocation; Sweden; Tonsillitis/*PX. .T Effect of patients' expectations on recovery from acute tonsillitis [see comments] .P JOURNAL ARTICLE. .W To investigate whether the personal attention paid to a patient can affect his or her subjective recovery from acute tonsillitis, a controlled study was performed on 100 patients consulting a doctor for this disease. At the consultation a randomly assigned experimental group (n = 50) was given more detailed information about the diagnosis, treatment and prognosis and also a more extensive physical examination than a control group (n = 50). At a follow-up interview two days later significantly more of the experimental group felt that their symptoms had improved (P less than 0.005) than the control group, significantly more felt that the treatment had helped them (P less than 0.005) and significantly more felt they had received sufficient information about their illness and treatment (P less than 0.001). A deliberate attempt to maximize the expectation effect was thus shown to influence the clinical course of acute tonsillitis, recorded as the degree of subjective improvement. .A Olsson B; Olsson B; Tibblin G. .I 201096 .U 90006505 .S Fam Pract 9001; 6(3):193-8 .M Attitude of Health Personnel/*; Diabetes Mellitus, Insulin-Dependent/CO/MO/*TH; England; Faculty, Medical/*; Human; Outcome and Process Assessment (Health Care); Physician's Practice Patterns; Physicians, Family/*PX. .T Doctors' beliefs and the management of insulin dependent diabetes: implications for sharing care. .P JOURNAL ARTICLE. .W There have been many studies of the health beliefs of patients but relatively few have considered the beliefs of doctors and the influence these have on the management of a disease. This paper reviews the evidence that such beliefs are important and reports a preliminary study examining differences in the beliefs of doctors as a function of their experience and chosen specialty. Thirty four general practitioner teachers responded to a questionnaire measuring beliefs about diabetes and its management. The results were compared with those of a previous study among hospital doctors with an interest in diabetes. In comparison with hospital doctors, general practitioner teachers had a more pessimistic outlook on diabetes, perceiving that the disease carried more risks and having less confidence that achieving goals of treatment would reduce these risks. In accord with these beliefs their approach to treatment was less rigorous than that of hospital-based doctors. These results have implications for shared care; such differences between groups of doctors are likely to be a barrier to the effective sharing of patient care. The results also add further strength to the view that doctors' beliefs about a disease and its management need to be considered alongside those of the patient to explain more of the variance in patient health outcomes. .A Kinmonth AL; Marteau TM. .I 201097 .U 90006506 .S Fam Pract 9001; 6(3):199-202 .M Education, Medical, Graduate/*; Emotions/*; Female; Human; Internship and Residency/*; Male; Physician-Patient Relations; Physician's Role; Physicians, Family/ED/*PX; Teaching/MT. .T The doctor and his feelings: a course for residents in family medicine. .P JOURNAL ARTICLE. .W A course on the doctor and his feelings was presented as part of a programme for family medicine residents. The course was led by family physicians and behavioural science professionals who taught as an integrated team. Various teaching techniques were utilized to highlight emotional aspects of the doctor-patient relationship to inexperienced residents. Pre- and post-course assessments suggested there were benefits in a short intensive course of this nature. Possible explanations for the findings are discussed. .A Rabinowitz S; Herz M; Granek M; Lehmann S; Pincus C; Maoz B. .I 201098 .U 90006507 .S Fam Pract 9001; 6(3):203-9 .M Attitude to Health; Health Promotion; Human; Life Style; New South Wales; Physician's Role/*; Physicians, Family/*; Primary Prevention/*; Public Opinion/*; Random Allocation; Role/*. .T Community views about the role of general practitioners in disease prevention. .P JOURNAL ARTICLE. .W The role of preventive medicine in reducing mortality and morbidity is now widely recognized. Although general practitioners appear to be in an excellent position to offer preventive care, there is evidence that they currently do not detect or intervene for common risk behaviours. One reason for this may be the general practitioner's perception that patients do not expect such preventive activities to be a part of the doctor's role. A postal survey of 309 people randomly selected from the community was undertaken to examine perceptions about the general practitioner's role in detection and intervention for smoking, alcohol abuse, emotional problems and hypertension. Responses to the survey from 264 usable questionnaires indicated that people in the community accepted the general practitioner's role in preventive care, with most respondents indicating that they would appreciate being asked about the risks examined, would like the offer of intervention and would try treatments in these areas offered by the doctor. Few respondents indicated that they would change doctors as a result of preventive activity. .A Slama KJ; Redman S; Cockburn J; Sanson-Fisher RW. .I 201099 .U 90006508 .S Fam Pract 9001; 6(3):210-6 .M Ambulatory Care Facilities/*UT; Child Health Services/*UT; Drug Therapy/*UT; Epidemiology; Human; Infant; Infant, Newborn; Physician's Practice Patterns; Prevalence; Sweden. .T Health complaints and drug consumption during the first 18 months of life. .P JOURNAL ARTICLE. .W Medical events of the first 18 months of life were studied in a group of 129 infants. Their medical files held at the child welfare clinic and at the surgery of the district physician as well as at the ear, nose and throat and paediatric departments were scrutinized. The parents were interviewed when their infants had reached an age of 18 months. The 129 infants were brought to the district nurse or doctor on a total of 2804 occasions. The majority of these visits were routine health checks. During the period in question, 57% needed medical attention for upper respiratory tract infection and 29% for acute otitis media. Most of the infants had been given the non-prescription remedies paracetamol and nose drops. Altogether 64% had received some form of antibiotic. A positive correlation was found between the number of visits as a patient made by the mother during her pregnancy and the number of visits on behalf of her baby during its first 18 months. .A Hakansson A. .I 201100 .U 90006509 .S Fam Pract 9001; 6(3):217-20 .M Anthropometry/*; Consanguinity/*; Female; Fetal Development/*; Gestational Age; Human; Infant, Newborn; Male; Random Allocation; Saudi Arabia; Support, Non-U.S. Gov't; Urban Population. .T Effects of consanguineous matings on anthropometric measurements of Saudi newborn infants. .P JOURNAL ARTICLE. .W The effects of parental consanguinity on gestation age and anthropometric measurements of 4497 Saudi newborn infants have been evaluated. The incidence of consanguineous matings was high, about 54.3%. For purposes of statistical analysis, marriages were classified into three groups based on degree of consanguinity. The results of the study reveal no significant effects of inbreeding on gestational age. Neither were any significant differences observed by type of marriage in weight, height or head, chest and mid-arm circumference at birth. It is suggested that inbreeding does not lead to significant effects of fetal growth among Saudi newborns. .A Saedi-Wong S; al-Frayh AR. .I 201101 .U 90006510 .S Fam Pract 9001; 6(3):221-3 .M Acetaminophen/*AD; Administration, Oral; Child; Child, Preschool; Family Practice/*; Human; Infant; Israel; Medication Errors; Self Administration; Urban Population. .T What's in a teaspoon? Underdosing with acetaminophen in family practice. .P JOURNAL ARTICLE. .W A study was made of 100 paediatric encounters in which an accompanying parent stated that the child had been given acetaminophen syrup during the preceding 24 hours. In 80% of cases a household teaspoon had been used to determine the amount of medication required. The volumes of these spoons were measured using a syringe. The range was from 1.5 to 5 cm3 with 79% containing 2 to 3 cm3. The mean volume was 2.95 cm3 (SD 0.79) and the median was 2.5 cm3. The mean dose administered was 62% of that recommended when the calculation was made according to age and 64% according to body weight. Much of the underdosing observed was due to parents' assumption that a household teaspoon contains 5 cm3 of acetaminophen syrup and also to a failure to correct for advancing age and increasing weight. .A Hyam E; Brawer M; Herman J; Zvieli S. .I 201102 .U 90006549 .S Gastroenterology 9001; 97(5):1083-9 .M Animal; Cats; Esophagogastric Junction/*PH; Female; Immune Sera/IM; Male; Muscle Relaxation/PH; Neuroregulators/PD; Peptide PHI/IM/*PH; Radioimmunoassay; Support, U.S. Gov't, P.H.S.; Vasoactive Intestinal Peptide/IM/*PH. .T Role of peptide histidine isoleucine in relaxation of cat lower esophageal sphincter. .P JOURNAL ARTICLE. .W Vasoactive intestinal peptide (VIP) is a candidate as an inhibitory neurotransmitter mediating relaxation of the lower esophageal sphincter (LES) because VIP antiserum reduces LES relaxation in response to neural stimulation. Vasoactive intestinal peptide antiserum, however, does not completely block LES relaxation. Thus it is possible that other neurotransmitters may be involved. Peptide histidine isoleucine has structural homologies with VIP, is synthesized with VIP from a common precursor protein, coexists in some nerve cells, and is coproduced with VIP in some tumors. In numerous organ systems VIP and peptide histidine isoleucine (PHI) produce similar effects, with PHI being less potent than VIP by approximately one log number. In the LES both VIP and PHI produce tetrodotoxin-resistant dose-dependent relaxation, with PHI being almost equipotent with VIP. We therefore tested the hypothesis that PHI may be a second neurotransmitter, partly responsible for relaxation of the cat LES, by using a highly specific rabbit PHI antiserum that exhibits minimal cross-binding with VIP, secretin, and glucagon. In 3 animals, LES and brain tissue were extracted in 0.1 N HCl and assayed with a PHI radioimmunoassay. The antiserum cross-reacted with cat brain and LES showing PHI concentrations greater than 100 ng/g, with the LES containing equal or greater concentrations of PHI than brain tissue. In other animals consecutive LES circular muscle strips were cut, mounted in 1-ml muscle chambers, and stimulated with 6-s square-wave trains of 0.1-, 0.2-, 0.4-, and 0.8-ms pulses at 1, 2, and 5 Hz. These parameters produced relaxation that was completely blocked by tetrodotoxin, and reduced by VIP antiserum, but not affected by adrenergic or cholinergic receptor antagonists. Some strips were incubated in 5% or 10% PHI antiserum, whereas others were incubated in the same concentration of preimmunization serum from the same animal. Incubation in normal serum did not significantly affect relaxation, whereas in the antiserum-treated strips, LES relaxation was reduced by a significant amount (20%-30%) at all parameters of stimulation tested. Incubation in antiserum however had no effect on relaxation induced by VIP (10(-8)-10(-6) M). These data suggest that PHI may play a role in LES relaxation induced by electrical stimulation. .A Biancani P; Beinfeld MC; Hillemeier C; Behar J. .I 201103 .U 90006550 .S Gastroenterology 9001; 97(5):1090-6 .M Adult; Aged; Colon/*ME; Fatty Acids, Volatile/*ME; Feces/*AN; Female; Gastrointestinal Contents/AN; Human; Intestinal Absorption; Intestines/*SU; Male; Middle Age; Postoperative Period; Support, Non-U.S. Gov't; Time Factors. .T Short-chain fatty acids in bowel contents after intestinal surgery [see comments] .P JOURNAL ARTICLE. .W Short-chain fatty acids are produced in the human colon by bacterial fermentation of dietary fibers and other saccharides escaping absorption in the small bowel. Short-chain fatty acid concentrations were determined together with production rates in 6- and 24-h incubations of intestinal outputs from 56 patients with various types of intestinal resections. Concentrations and 6- and 24-h production rates in feces from 9 healthy persons (controls; median +/- SD) were 98.9 +/- 21.4 mmol/L and 17.2 +/- 5.1 and 9.3 +/- 1.5 mmol/L.h, respectively. Colectomized patients with short bowel syndrome had extremely low concentrations (0.8 mmol/L) compared with controls (p less than 10-5), patients with ileostomy (p = 0.003), and ileal reservoirs (p less than 10-5), and showed low 6- and 24-h production rates (1.5 and 0.9 mmol/L.h, respectively; p less than 10-5 vs. controls). Short-chain fatty acids in ileostomic digesta (11.1 mmol/L) were decreased (p = 0.011) compared with outputs from ileal reservoirs (51.5 mmol/L), although production rates were in the same order of magnitude--all below control values (p less than 0.001). Patients partially colectomized and patients with small bowel bypass or short bowel syndrome with preserved colon had normal fecal concentrations with decreased production rates of short-chain fatty acids vs. controls (p less than 0.01). Only minor changes in ratios between individual acids were found. Reciprocal values of short-chain fatty acid concentrations correlated to volumes of outputs from both small intestine (r = 0.86, p less than 10-6) and colon (r = 0.79, p less than 10-6) when results were cumulated. It is concluded that partial resections of colon and the small bowel do not influence the fecal concentration level of short-chain fatty acids as long as colon is not totally resected. .A Mortensen PB; Hegnhoj J; Rannem T; Rasmussen HS; Holtug K. .I 201104 .U 90006552 .S Gastroenterology 9001; 97(5):1101-7 .M Animal; Dogs; Eating; Female; Gastric Emptying/*PH; Gastrins/*BL; Gastrointestinal Motility/*PH; Motilin/*BL; Noise/AE; Pancreatic Polypeptide/*BL; Somatostatin/*BL; Stress/*PP; Support, Non-U.S. Gov't. .T Stress-induced changes in gastric emptying, postprandial motility, and plasma gut hormone levels in dogs. .P JOURNAL ARTICLE. .W The influence of acoustic stress on postprandial gastrointestinal motility, gastric emptying, and plasma gastrin, pancreatic polypeptide, motilin, and somatostatin was evaluated in conscious dogs. Six dogs were equipped with strain-gauge transducers and were exposed from 1-3 h after the meal to prerecorded music (80-90 dB broad frequency noise), which produced a significant (p less than or equal to 0.05) lengthening of the gastric (31.2%) and jejunal (37.0%) postprandial pattern. In 4 other dogs with gastric cannula, a 2-h session of acoustic stress beginning just after eating a radiolabeled standard meal induced a slowing of gastric emptying of both liquid (45.7%) and solid (47.1%) phases of the test meal when measured 0.5 h after feeding. In contrast, when measured 2 h after feeding, similar values of gastric emptying of liquids and solids were observed in stressed and control animals. Compared with controls, the postprandial increases of plasma gastrin and pancreatic polypeptide levels were significantly enhanced in stressed animals and occurred early (15 min after the meal). Although postprandial decrease in plasma motilin was unchanged by acoustic stress, the rise in plasma somatostatin level was significantly (p less than or equal to 0.05) prolonged in stressed dogs. These results indicate that acoustic stress affects gastric and intestinal postprandial motility in dogs, delaying the recovery of the migrating motor complex pattern, inducing a transient slowing of gastric emptying, and enhancing the feeding-induced release of gastrin, pancreatic polypeptide, and somatostatin. Such hormonal changes might be due to a direct effect of stress rather than being the consequence of acoustic stress-induced slowing of gastric emptying. .A Gue M; Peeters T; Depoortere I; Vantrappen G; Bueno L. .I 201105 .U 90006553 .S Gastroenterology 9001; 97(5):1108-14 .M Animal; Antipyrine/AA; Autoradiography; Carbon Radioisotopes/DU; Gastric Mucosa/BS; Hypertension, Portal/*PP; Ligation; Male; Portal Vein/SU; Rats; Rats, Inbred Strains; Regional Blood Flow; Stomach/*BS; Support, Non-U.S. Gov't. .T Autoradiographic study of the regional distribution of gastric blood flow in portal hypertensive rats. .P JOURNAL ARTICLE. .W This study measures regional gastric blood flow in portal hypertensive rats at three separate periods after portal vein ligation using quantitative autoradiography with 14C-labeled iodoantipyrine. The level of corpus mucosal blood flow was significantly reduced in 3-day portal vein-ligated animals compared with sham-operated control animals (30.4 +/- 2.3 vs. 47.1 +/- 5.6 ml/100 g.min). There was no significant difference in corpus mucosal blood flow between portal vein-ligated and sham-operated animals at 7- and 28-day periods, although the level of perfusion was higher in the 28-day portal vein-ligated group. There was no significant difference in antral mucosal or muscle blood flow between portal hypertensive and control animals at any of the study periods. We conclude that the acute period after portal vein ligation is associated with a reduced corpus mucosal microcirculation but that this effect is not sustained in portal hypertensive animals studied at later intervals after portal vein ligation. .A Geraghty JG; Angerson WJ; Carter DC. .I 201106 .U 90006555 .S Gastroenterology 9001; 97(5):1121-9 .M Animal; Arteries/PH/SU; Gastric Mucosa/*BS/PA; Guinea Pigs; Ischemia/CO; Ligation; Necrosis; Stomach Ulcer/*ET; Support, Non-U.S. Gov't. .T Ulcers produced by ligation of individual gastric mucosal arteries in the guinea pig. .P JOURNAL ARTICLE. .W It is not known whether or not individual gastric mucosal arteries are end-arteries. We therefore occluded single mucosal guinea pig arteries, resulting in necrosis of the whole thickness of mucosa in the area supplied by the artery in 25 of 33 cases (76%). However, there were no cases of necrosis in 33 control sham ligations performed in the same animals (p less than 0.001). In another group, ligation of two or three adjacent mucosal arteries resulted in necrosis in 10 of 11 cases (p less than 0.0001), against 0 necrosis in 11 sham ligations. Killing the animals at varying intervals showed that after 1 day the mucosa was necrotic, after 2 days it was shed, and later it might perforate. We conclude that many mucosal arteries in the guinea pig may behave as functional end-arteries. How these findings may pertain to ulceration is discussed in relation to (a) the existence of atypical mucosal arteries found in the ulcer-bearing areas in humans and (b) the role of the muscularis mucosae on arterioles perforating it in both humans and other species. .A Piasecki C; Thrasivoulou C; Rahim A. .I 201107 .U 90006557 .S Gastroenterology 9001; 97(5):1135-46 .M Animal; Denervation; Gastrins/AN; Gastrointestinal Motility/*PH; Guinea Pigs; Intestine, Small/*IR; Myenteric Plexus/*PH; Nerve Regeneration/PH; Peptides/AN; Somatostatin/AN; Splanchnic Nerves/*PH; Support, Non-U.S. Gov't; Vasoactive Intestinal Peptide/AN. .T Migration of the myoelectric complex after interruption of the myenteric plexus: intestinal transection and regeneration of enteric nerves in the guinea pig. .P JOURNAL ARTICLE. .W The effects of surgical interruption of the myenteric plexus (myectomy), extrinsic denervation of a length of small intestine, or transection and reanastomosis of the intestinal wall on migration of phase III of the migrating myoelectric complex was studied in guinea pigs. In addition, the recovery of phase III migration and the regrowth of intestinal nerves and muscle across the reanastomosis was studied at various times up to 60 days after surgery. At 6-9 days after surgery, phase III did not migrate past the myectomy during 50%-60% of recorded migrating myoelectric complexes and transection and reanastomosis of the intestinal wall blocked aboral progression of phase III in 90% of cases. Extrinsic denervation did not alter phase III migration through the denervated segment. Phase III migration past the reanastomosis recovered with time after surgery; 80% recovery occurred by 60 days after surgery. Immunoreactivities for vasoactive intestinal peptide, gastrin-releasing peptide, and somatostatin were used as markers for intestinal nerves that were cut by transaction. Immunoreactivities for vasoactive intestinal peptide and gastrin-releasing peptide are contained in myenteric neurons that project in an oral to anal direction to other myenteric ganglia and to the circular muscle. Immunoreactivity for somatostatin is contained in nerve fibers projecting aborally to other myenteric ganglia. At 7-15 days after surgery, there were accumulations of immunoreactivities for vasoactive intestinal peptide, gastrin-releasing peptide, and somatostatin in nerve fibers on the oral side of the reanastomosis, but nerve fibers containing these peptides were not observed in myenteric ganglia or circular muscle close to the anal edge. At 23-28 days, immunoreactivities for vasoactive intestinal peptide, gastrin-releasing peptide, and somatostatin nerve fibers were traced across the reanastomosis and nerve terminals were detected in ganglia and muscle close to the lesion on the anal side. Nerve fibers traversed the lesion in all cases at 57-60 days and vasoactive intestinal peptide-, gastrin-releasing peptide-, and somatostatin-immunoreactive nerve terminals were detected in the first two to three rows of myenteric ganglia on the anal side. Regrowth of intestinal muscle followed a similar time-course to that observed for nerves. These data suggest that interruption of the myenteric plexus alone does not completely block phase III migration. In addition, recovery of phase III migration past a reanastomosis is associated with a restoration of both nervous and mechanical connections. .A Galligan JJ; Furness JB; Costa M. .I 201108 .U 90006558 .S Gastroenterology 9001; 97(5):1147-58 .M Animal; Aspirin/*TO; Cold/*AE; Female; Gastric Acid/*SE; Gastric Mucosa/*BS/ME; Male; Prostaglandins/*ME; Rats; Rats, Inbred Strains; Regional Blood Flow; Stomach Ulcer/*ET. .T Potentiation of aspirin-induced gastric lesions by exposure to cold in rats. Role of acid secretion, mucosal blood flow, and gastric mucosal prostanoid content. .P JOURNAL ARTICLE. .W We investigated the mechanism by which exposure to cold sensitizes rats to the formation of gastric lesions after a low dose of aspirin (50 mg/kg). Six times more lesions were produced by aspirin plus cold than by aspirin alone. Three hypotheses were studied to explain the synergism of aspirin plus cold on lesion formation: gastric acid hypersecretion, reduced gastric mucosal blood flow, and decreased prostanoid synthesis by the stomach. Cold, and cold plus aspirin, stimulated gastric acid secretion (to a similar extent), whereas aspirin had no effect. Gastric mucosal blood flow, measured by the hydrogen gas clearance method, was decreased by cold, aspirin, and aspirin plus cold, and the extent of decrease was similar. Prostanoid generation [prostaglandin E2 (PGE2), PGF2 alpha, 6-keto PGF1 alpha, and thromboxane B2] by the gastric corpus mucosa was not affected by cold, but was reduced equally (by at least 90%) in animals receiving aspirin alone or aspirin plus cold. After oral administration of aspirin, the plasma contained mostly salicylic acid (98%), whereas the gastric mucosa contained mostly aspirin (80%-85%). We conclude that the synergism of aspirin plus cold on the formation of gastric lesions probably results from the combined effects of three factors: increased secretion of acid (because of exposure to cold) that is in contact with a gastric mucosa in which blood flow is reduced (because of exposure to cold or to aspirin), and in which the synthesis of cytoprotective prostaglandins is inhibited (by aspirin). Such mucosa may be particularly vulnerable to the damaging effect of hyperacidity. .A Robert A; Leung FW; Kaiser DG; Guth PH. .I 201109 .U 90006559 .S Gastroenterology 9001; 97(5):1159-63 .M Adult; Cholecystokinin/*BI/*BL; Chromatography, Gel; Female; Food; Gastrins/*BI/*BL; Glycine/BI; Human; Male; Peptide Fragments; Protein Precursors/*BI; Protein Processing, Post-Translational/PH; Radioimmunoassay; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Glycine-extended processing intermediates of gastrin and cholecystokinin in human plasma. .P JOURNAL ARTICLE. .W The biosynthesis of biologically active gastrin and cholecystokinin (CCK) requires the formation of carboxyl-terminally amidated peptides from glycine-extended precursors of gastrin and CCK. In previous studies we and others have identified and characterized glycine-extended forms of gastrin (Ggly) and CCK (CCK-gly) in the human gastrointestinal tract. To explore the potential biologic importance of these peptides in humans, we examined their release into the circulation. Ingestion of a standard meal induced a biphasic rise in plasma G/CCK-gly concentration, but only the initial increase correlated with gastrin release. Intraduodenal lipid infusion caused a selective rise in CCK-gly immunoreactivity with no increase in gastrin or G-gly. Gel filtration chromatography revealed that the predominant molecular form of G/CCK-gly in basal plasma coeluted with CCK8-gly, but in response to meal stimulation, increases in other molecular forms were noted. Measurement of glycine-extended intermediates of progastrin and procholecystokinin posttranslational processing in plasma may aid in determining their physiologic importance in health and disease. .A DelValle J; Sugano K; Yamada T. .I 201110 .U 90006560 .S Gastroenterology 9001; 97(5):1164-70 .M Animal; Colon/PH; Epithelium/PH; Hydrogen-Ion Concentration; Ileum/PH; Intestinal Absorption/*PH; Jejunum/PH; Male; Osmolar Concentration; Perfusion; Polyethylene Glycols/*PK; Rats; Rats, Inbred F344; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Mechanisms of polyethylene glycol 400 permeability of perfused rat intestine. .P JOURNAL ARTICLE. .W Abnormal permeability to polyethylene glycol 400 (PEG 400) has been demonstrated in various disorders with defective intestinal barrier functions. To understand the basic mechanisms of PEG 400 permeability, we compared PEG 400 permeation in different segments of the intestine and studied the kinetics and influence of intraluminal factors on PEG 400 absorption in vivo in perfused intestinal segments of the rat. The permeation rate of PEG 400 was dependent on the luminal concentration (y = 12.99x + 3.5; r = 0.97), indicating that passive movement is the mechanism involved in PEG 400 absorption. Changing the perfusate pH from 6 to 7.4 or modifying the unstirred water layer resistance by changing luminal flow rate did not affect PEG 400 absorption. When luminal osmolarity was varied from 0.225 to 0.6 osmol/L, higher osmolarity decreased both water and PEG 400 absorption (p greater than 0.01). The relationship between PEG 400 and water absorption at different osmolarities was linear (y = 0.9x + 5.7; r = 0.98). At a luminal osmolarity of 0.3 osmol/L 43% of PEG 400 permeation was mediated by passive diffusion and 57% was mediated by solvent drag. Increasing water absorption by decreasing luminal osmolarity resulted in proportional increase of PEG 400 permeation through solvent drag or convection. The solvent drag reflection coefficient (sigma f) for PEG 400 permeation of the jejunum was 0.1. Taurocholic acid (10 mM) alone or with oleic acid (2.5 mM) did not affect PEG 400 absorption. Permeabilities of 1 mM PEG 400 and water were similar in jejunum and ileum but were markedly increased in the colon (p greater than 0.01). These studies demonstrate that PEG 400 is absorbed by both passive diffusion and by solvent drag, with the latter accounting for a greater fraction of the absorptive drive under normal conditions. Polyethylene glycol 400 uses aqueous pathways for its permeation across the intestinal epithelium. .A Krugliak P; Hollander D; Ma TY; Tran D; Dadufalza VD; Katz KD; Le K. .I 201111 .U 90006562 .S Gastroenterology 9001; 97(5):1181-5 .M Balloon Dilatation/*; Deglutition Disorders/*PP; Esophageal Spasm, Diffuse/PP; Esophagus/*PP; Human; Manometry; Pressure; Prospective Studies. .T Manometric responses to balloon distention in patients with nonobstructive dysphagia. .P JOURNAL ARTICLE. .W The manometric responses to graded intraesophageal balloon distention were studied in 30 patients with symptoms of intermittent dysphagia but without evidence of structural narrowing on barium swallow or endoscopy, or both. These studies were compared with those performed in 10 normal volunteers. Using a manometric catheter with a balloon of reproducible dimension, balloon distention produced a sustained pressure proximal to the distended esophageal balloon in 28 of 30 (93%) patients and 9 of 10 (90%) normal volunteers. Patients with dysphagia had the reproduction of their characteristic symptom during balloon distention in 23 of 30 (76%) cases. Atypical symptoms not characteristic of the patients' usual dysphagia developed in the other 4 patients with dysphagia and in all controls. There were no electrocardiographic changes during balloon distention and symptoms were immediately reversible with balloon deflation. Repeated simultaneous contractions consistent with spasm distal to the distending esophageal balloon occurred in 21 of 30 (70%) patients with dysphagia but in no normal volunteers (p less than 0.05). Dysphagia reproduction was associated with the finding of repeated simultaneous contractions distal to the intraesophageal balloon being found in 20 of 30 (66%) patients (p less than 0.05). Distal activity during balloon distention of the esophagus is associated with dysphagia reproduction in a significant number of patients without any other explanation for their symptom. The development of distal spasm in patients with intermittent dysphagia suggests an abnormality of neural control that may be important in the pathophysiology of dysphagia in these patients. .A Deschner WK; Maher KA; Cattau EL Jr; Benjamin SB. .I 201112 .U 90006564 .S Gastroenterology 9001; 97(5):1193-204 .M Animal; Cell Movement; Intestinal Absorption; Jejunum/*DE/UL; Male; Microscopy, Electron; Microvilli/DE; Phytohemagglutinins/*TO; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Repair of microvilli in the rat small intestine after damage with lectins contained in the red kidney bean. .P JOURNAL ARTICLE. .W That microvilli of intestinal absorptive cells in the duodenum and jejunum are disrupted by acute challenge with lectins contained in raw kidney beans (RKB) was shown nearly 10 yr ago by light microscopy. However, the precise morphologic damage produced by RKB has not been characterized, and it is not known whether microvilli, once damaged, undergo repair. We have examined these issues by challenging rats with suspensions of 300 mg of RKB, boiled beans, or standard laboratory chow by orogastric lavage. Microvillus length was measured in electron micrographs from 6 to 20 h after challenge. Epithelial cell migration was determined by autoradiography after injection of [3H]thymidine. After challenge with RKB, microvilli (a) showed extensive vesiculation along the length of villi 2-4 h after challenge; (b) were reduced significantly in length along the entire villus 6 h after challenge; and (c) were near normal in length by 20 h after challenge. Microvillus length was also reduced significantly 6 h after challenge with boiled beans. The rate of cell migration was not accelerated by treatment with RKB. These data suggest that damage to microvilli caused by 300 mg of RKB is self-limited and reversible; microvilli once damaged by RKB are repaired. Repair of microvilli is due to intrinsic reparative processes rather than accelerated replacement of damaged cells. We speculate that microvilli may be repeatedly damaged and repaired after ingestion of dietary lectins. .A Weinman MD; Allan CH; Trier JS; Hagen SJ. .I 201113 .U 90006565 .S Gastroenterology 9001; 97(5):1205-9 .M Alcohol, Ethyl/AD/BL/*PK; Comparative Study; Gastrectomy/*; Human; Intestines/ME; Liver/ME; Male; Oxidation-Reduction; Stomach/*ME; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Gastric origin of the first-pass metabolism of ethanol in humans: effect of gastrectomy. .P JOURNAL ARTICLE. .W The areas under the curve (AUCs) of blood ethanol concentrations are much smaller after oral than after intravenous administration of a small dose of ethanol. To study whether this difference is due to ethanol oxidation in the stomach, in the small intestine, or during first pass through the liver, we compared the AUCs after random administration of the same ethanol dose by the intravenous, oral, and intraduodenal routes to 5 abstaining alcoholics and via the two former routes to 10 subjects with Billroth II subtotal gastrectomy. In the nonoperated subjects, the AUCs after an ethanol dose (0.15 g/kg) given orally were 17% (p less than 0.01) of those achieved intravenously, in spite of the fact that greater than 99% of the dose had disappeared from the stomach at the completion of the AUC. By contrast, the AUCs after intraduodenal administration did not differ from those produced intravenously, indicating that neither the intestine nor the liver make a detectable contribution to this first-pass metabolism. Moreover, gastrectomy completely abolished the first-pass metabolism of ethanol. Gastric metabolism decreases the bioavailability of the ingested alcohol and thus attenuates its systemic toxicity. The abolition of this "protective barrier" in gastrectomized patients may increase their vulnerability to ethanol. .A Caballeria J; Frezza M; Hernandez-Munoz R; DiPadova C; Korsten MA; Baraona E; Lieber CS. .I 201114 .U 90006568 .S Gastroenterology 9001; 97(5):1229-35 .M Aged; Aged, 80 and over; Anesthesia, General; Cholelithiasis/*TH; Ethers/*TU; Female; Human; Lithotripsy/*; Male; Middle Age; Posture; Solvents/TU; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Time Factors. .T Extracorporeal shock-wave lithotripsy and methyl tert-butyl ether for partially calcified gallstones. .P JOURNAL ARTICLE. .W To explore the possibility that gallbladder stone fragments might be able to be safely dissolved using methyl tert-butyl ether immediately after extracorporeal shock-wave lithotripsy (ESWL), a feasibility study in 8 patients with one to four partially calcified gallbladder stones was performed. The gallstones averaged 2.2 cm in diameter (range 1.3-3 cm) and contained layered or diffuse calcium detectable by computed tomography scan only (7 patients) or plain film (1 patient). After a 5F (1.7 mm) pigtail catheter was placed percutaneously into the gallbladder, ESWL fragmentation was performed using a renal stone lithotriptor. The patients were under general anesthesia and in the prone position on a support gantry designed for gallbladder stone ESWL. Following ESWL, methyl tert-butyl ether was infused and aspirated via the gallbladder catheter until no further stone material was radiologically detectable or could be dissolved. After 8-26 h (mean = 13 h) of methyl tert-butyl ether therapy, no radiologically detectable gallstones remained in 6 of 8 patients. Shell fragments of three peripherally calcified stones in 1 patient and the densely calcified, predominantly pigment stone in a second patient were refractory to combined therapy. Both ESWL and treatment with methyl tert-butyl ether were well tolerated in all patients, although bile leakage after catheter removal occurred in 3 patients, one of whom was treated by cholecystectomy. Additional measures to prevent bile leakage may be advisable if these two modalities are to be used in tandem. We found no evidence, however, that predissolution stone fragmentation with ESWL predisposed the gallbladder to either mucosal damage by methyl tert-butyl ether or increased absorption of it. .A Peine CJ; Petersen BT; Williams HJ; Bender CE; Patterson DE; Segura JW; Nagorney DM; Warner MA; Thistle JL. .I 201115 .U 90006569 .S Gastroenterology 9001; 97(5):1236-47 .M Animal; Bile Ducts, Intrahepatic/*CY/ME; Cell Separation/MT; Epithelium/CY; Immunohistochemistry; Male; Microscopy, Electron; Microscopy, Electron, Scanning; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Isolation and morphologic characterization of bile duct epithelial cells from normal rat liver. .P JOURNAL ARTICLE. .W To study directly the functions of the cells that line the bile ducts inside the liver, we developed a new technique for isolating intrahepatic bile duct epithelial cells (IBDECs) from normal rat liver. Parenchymal and nonparenchymal cells were separated from whole liver by enzymatic digestion and mechanical disruption; subpopulations of individual nonparenchymal cells then were isolated by serial counter-flow elutriation, isopycnic centrifugation, and immunoaffinity separation with a specific monoclonal antibody against an antigen on the plasma membrane of IBDECs. Using this approach, we isolated 1.2 +/- 0.2 x 10(6) (mean +/- SE) viable (greater than 95% trypan blue exclusion) cells, greater than 95% of which were identified as IBDECs by morphologic appearance and specific cytochemical markers. The IBDECs averaged 7.4 +/- 0.16 microM in diameter and retained their in situ appearance, including morphologic polarity. They appeared as single cells or as cell doublets attached by tight junctions that excluded ruthenium red. Microvilli were abundant and were restricted to the apical (i.e., luminal) domain of the plasma membrane. Coated pits were observed on both apical and basolateral cell surfaces. Internally, IBDECs contained a well-developed system of organelles, including mitochondria, Golgi, and discrete types of vesicles, such as coated vesicles, multivesicular bodies, and lysosomes. These results indicate that a highly purified suspension of viable, morphologically intact, and polar IBDECs can be prepared from normal rat liver using a novel approach that separates liver cells on the basis of size, density, and specific membrane components. The availability of such a model will allow experimental studies to be performed directly on IBDECs, an approach that has not previously been possible. .A Ishii M; Vroman B; LaRusso NF. .I 201116 .U 90006570 .S Gastroenterology 9001; 97(5):1248-60 .M Animal; Bile Ducts, Intrahepatic/*CY/ME; Cell Separation; Cholestasis/PA; Epithelium/CY; Gamma-Glutamyltransferase/ME; Hyperplasia; Immunohistochemistry; Keratin/ME; Liver/*CY/ME; Male; Microscopy, Electron; Phenotype; Rats; Rats, Inbred Strains; Support, U.S. Gov't, P.H.S.. .T Isolation of a nonparenchymal liver cell fraction enriched in cells with biliary epithelial phenotypes. .P JOURNAL ARTICLE. .W In the present study we have isolated and purified fractions of nonparenchymal liver cells were isolated by collagenase-pronase digestion of the biliary and connective hepatic tissue, which remained undissociated after collagenase perfusion of the liver. Fractionation of the nonparenchymal fractions was then achieved by centrifugal elutriation. Both normal rats and rats with proliferated bile duct-like structures, which were induced either by a 14-day bile duct ligation or by feeding 0.1% alpha-naphthylisothiocyanate for 28 days, were used in these studies. Using a normal rat liver, the fraction richest in biliary epithelial cells was that obtained at a pump flow rate of 36-40 ml/min. In this fraction 1.8-3.8 x 10(6) cells per liver were recovered and up to 55% of them were positive for gamma-glutamyl transpeptidase and cytokeratins 7 and 19, all of which were histochemically or immunohistochemically detected solely in the biliary structures in the intact rat liver. When the nonparenchymal cells were isolated from hyperplastic livers, the number of cells recovered in such a fraction ranged from 12 to 19 x 10(6) per liver, and as many as 60%-85% of the cells expressed phenotypes of biliary epithelial cells. These results indicate that (a) by centrifugal elutriation a fraction of nonparenchymal cells enriched in cells with biliary epithelial phenotypes can be obtained from rat liver and (b) the hepatic hyperplasia induced by biliary obstruction or alpha- naphthylisothiocyanate feeding is a useful and valid strategy for improving both the yield and the purity of the isolated biliary epithelial cells. .A Alpini G; Lenzi R; Zhai WR; Liu MH; Slott PA; Paronetto F; Tavoloni N. .I 201117 .U 90006575 .S Gastroenterology 9001; 97(5):1288-93 .M Adult; Azathioprine/TU; Comparative Study; Drug Therapy, Combination; Female; Hepatitis B Surface Antigens/*AN; Hepatitis, Chronic Active/*DT; Human; Menopause/*DE; Middle Age; Prednisone/AE/*TU; Prognosis; Retrospective Studies. .T Prognosis of corticosteroid-treated hepatitis B surface antigen-negative chronic active hepatitis in postmenopausal women: a retrospective analysis. .P JOURNAL ARTICLE. .W To determine the consequences of corticosteroid treatment in postmenopausal patients with severe hepatitis B surface antigen-negative chronic active hepatitis, the findings in 43 such patients (mean age, 59 +/- 2 yr) were compared retrospectively to those in 46 premenopausal counterparts (mean age, 31 +/- 2 yr) after similar durations of initial (19 +/- 2 vs. 18 +/- 2 mo) and subsequent (48 +/- 8 vs. 63 +/- 11 mo) therapy. Postmenopausal patients entered remission as frequently as premenopausal women during initial treatment (81% vs. 83%, p = 0.9), deteriorated as commonly (7% vs. 7%), and developed drug-related complications as frequently (49% vs. 33%, p = 0.14). Postmenopausal women, however, had a higher cumulative frequency of complications (77% vs. 48%, p less than 0.01) and a greater occurrence of multiple complications (44% vs. 13%, p less than 0.01) than premenopausal counterparts during follow-up. Vertebral compression occurred more frequently (23% vs. 7%, p = 0.05), and lumbar spine densities were below the spontaneous fracture threshold more commonly (85% vs. 22%, p less than 0.002). Longer initial and cumulative durations of therapy were associated with the development of complications. We conclude that initial corticosteroid treatment is as safe and effective in postmenopausal women as in premenopausal counterparts. Postmenopausal women, however, have a higher cumulative frequency of complications long-term and a lower net benefit-risk ratio than comparably treated premenopausal women. .A Wang KK; Czaja AJ. .I 201118 .U 90006576 .S Gastroenterology 9001; 97(5):1294-9 .M Animal; Argipressin/TU; Diuresis/DE; Kidney/PH; Liver Cirrhosis, Experimental/*CO; Male; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't; Vasopressins/*AI/SE; Water-Electrolyte Imbalance/*DT/ET. .T Blockade of the hydroosmotic effect of vasopressin normalizes water excretion in cirrhotic rats. .P JOURNAL ARTICLE. .W Water retention in cirrhosis has classically been considered to be due to a low distal fluid delivery secondary to increased proximal sodium reabsorption. However, recent studies showing high plasma vasopressin levels in patients and rats with cirrhosis, ascites, and dilutional hyponatremia suggest that a nonosmotic vasopressin hypersecretion could be an alternative mechanism. To investigate the role of vasopressin in water retention in cirrhosis, the renal ability to excrete a water load (50 ml/kg body wt), as estimated by the minimum urinary osmolality and the percentage of the water load excreted during 3 h, was assessed in 10 control rats and in 20 cirrhotic rats with ascites and impaired water excretion and high urinary excretion of vasopressin. Twenty-four hours later, the same procedure was repeated in cirrhotic rats 20 min after the subcutaneous injection (30 micrograms/kg body wt) of d(CH2)5Tyr(Et) VAVP, an antagonist of the hydroosmotic effects of vasopressin (10 rats), or the vehicle (10 rats). Treatment with the vasopressin antagonist normalized water excretion in 9 of the 10 rats. No significant changes in renal water metabolism were observed in the group of rats given the vehicle. These results indicate that vasopressin hypersecretion is the predominant mechanism of the impairment in water excretion in rats with experimental cirrhosis and ascites. .A Claria J; Jimenez W; Arroyo V; Guarner F; Lopez C; La Villa G; Asbert M; Rivera F; Rodes J. .I 201119 .U 90006577 .S Gastroenterology 9001; 97(5):1300-3 .M Animal; Autoradiography; Carbon Radioisotopes/DU; Cell Hypoxia/*; Liver/*ME; Mice; Mice, Inbred Strains; Misonidazole/*PK; Oxygen/ME; Support, Non-U.S. Gov't; Tritium/DU. .T Misonidazole binding in murine liver tissue: a marker for cellular hypoxia in vivo. .P JOURNAL ARTICLE. .W The hepatic microcirculation is believed to cause variable cellular oxygenation within the organ. In this study a marker of cellular hypoxia was used to demonstrate liver oxygen tension gradients in vivo. Covalent binding of misonidazole adducts to cellular macromolecules is enhanced by hypoxia. Autoradiographs of liver from mice treated with radiolabeled misonidazole demonstrated enhanced binding of adducts within hepatocytes surrounding hepatic veins. Livers from both hypoxic and normal mice had characteristic autoradiographic grain patterns reflecting regional oxygen tension variation in vivo. Differential binding of misonidazole adducts formed in hypoxic cells could have an application in studies of liver physiology and biochemistry. .A Maxwell AP; MacManus MP; Gardiner TA. .I 201120 .U 90006579 .S Gastroenterology 9001; 97(5):1313-8 .M Case Report; Chromatography, High Pressure Liquid; Female; Human; Insulinoma/*AN/SC; Islet Cell Tumor/*AN; Liver/AN; Liver Neoplasms/AN/*SC; Middle Age; Pancreas/AN; Pancreatic Hormones; Pancreatic Neoplasms/*AN; Radioimmunoassay/MT. .T High plasma pancreastatinlike immunoreactivity in a patient with malignant insulinoma. .P JOURNAL ARTICLE. .W High levels of pancreastatinlike immunoreactivity were detected in the plasma (2.9 pmol/ml, greater than 200-fold the normal level), pancreas (2.9 nmol/g wet wt, greater than 450-fold the normal level), and liver (1.6 nmol/g wet wt) of a patient with pancreatic insulinoma with metastasis to the liver by a sensitive and specific radioimmunoassay for human pancreastatin. Antiserum was produced against the C-terminal fragment of human pancreastatin-(24-52), which was synthesized according to the sequence of human chromogranin A corresponding to that of pancreastatin. With the antiserum, intense immunocytochemical staining was detected in the tumors. Sephadex G-50 gel filtration showed that the tumors and plasma contained two molecular forms of pancreastatinlike immunoreactivity--a molecular form coeluted with synthetic human pancreastatin-52 and a larger molecular form (Mr approximately 12,000-15,000). The smaller form eluted in the same position as synthetic human pancreastatin-52 on reverse-phase high-performance liquid chromatography. .A Tateishi K; Funakoshi A; Jimi A; Funakoshi S; Tamamura H; Yajima H; Matsuoka Y. .I 201121 .U 90006583 .S Gastroenterology 9001; 97(5):1331-6 .M Adult; Caerulein/DU; Cholecystokinin/*AI; Food; Gallbladder/*DE/PH; Human; Infusions, Intravenous; Male; Proglumide/PD; Receptors, Cholecystokinin/*DE; Support, Non-U.S. Gov't. .T Effects of loxiglumide on gallbladder emptying in healthy volunteers. .P JOURNAL ARTICLE. .W This study evaluates the effects of the specific cholecystokinin receptor antagonist loxiglumide on gall-bladder emptying after a meal or after intravenous infusion of caerulein in humans. Ten healthy male volunteers were studied five times on separate days. The following five studies were performed in randomized order: (a) caerulein was intravenously infused at doses increasing from 7.5 to 120 ng/kg.h without the antagonist; (b) in addition to increasing doses of caerulein, loxiglumide was given intravenously at doses of 0.2, 1.0, or 5.0 mg/kg.h; (c) a solid-liquid 800-kcal meal was given without loxiglumide; (d) the 800-kcal meal was given with simultaneous infusion of 1 or 5 mg/kg.h loxiglumide; and (e) loxiglumide (5 mg/kg.h) was given. without caerulein or the test meal. Gallbladder volume was measured by ultrasound. Loxiglumide dose-dependently inhibited gallbladder emptying induced by caerulein or the meal. High doses of the antagonist did not only abolish meal-induced gallbladder emptying but increased gallbladder volume after administration of caerulein or the meal when compared with prior fasting values. The antagonist given alone markedly increased gallbladder volumes compared with prior fasting values. In conclusion, given alone markedly increased gallbladder volumes compared with prior fasting values. In conclusion, cholecystokinin is the hormone primarily and mainly responsible for mediation of gallbladder emptying after a regular meal. Cholecystokinin might also play a physiologic role in the regulation of the fasting tone of the gallbladder. .A Niederau C; Heintges T; Rovati L; Strohmeyer G. .I 201122 .U 90006584 .S Gastroenterology 9001; 97(5):1337-9 .M Animal; Bile Ducts, Intrahepatic/*CY; Cell Separation/MT; Epithelium/CY; Rats. .T Isolation of intrahepatic bile duct epithelial cells: clues for function. .P JOURNAL ARTICLE. .A Jones AL; Schmucker DL. .I 201123 .U 90006590 .S Gastroenterology 9001; 97(5):1345-6 .M Carbachol/*PD; Cell Line; Colon/*CY; Human; In Vitro; Mucus/SE; Receptors, Gastrointestinal Hormone/ME; Vasoactive Intestinal Peptide/*PD. .T Synergism between vasoactive intestinal polypeptide and carbachol-mediated responses in a human mucus-secreting colonic epithelial cell line. .P JOURNAL ARTICLE. .A Barrett KE; Dharmsathaphorn K. .I 201124 .U 90006591 .S Gastroenterology 9001; 97(5):1353-4 .M Gastroscopy; Human; Stomach Neoplasms/*DI. .T Radiology and endoscopy complementary in early gastric cancer [letter] .P LETTER. .A Ott DJ; Gelfand DW; Chen YM. .I 201125 .U 90006593 .S Gastroenterology 9001; 97(5):1354-6 .M Crohn Disease/*ET; Human; Mycobacterium/*IP; Mycobacterium Infections/*. .T Mycobacteria as the cause of Crohn's disease [letter; comment] .P COMMENT; LETTER. .A Graham DY; Markesich DC; Yoshimura HH. .I 201126 .U 90006594 .S Gastroenterology 9001; 97(5):1356-7 .M Animal; Colitis/*DT; Prostaglandins E, Synthetic/*TU; Rats; 16,16-Dimethylprostaglandin E2/*TU. .T Effect of prostaglandin E2 in experimental colitis [letter; comment] .P COMMENT; LETTER. .A Rhodes J; Psaila JV. .I 201127 .U 90006595 .S Gastrointest Endosc 9001; 35(5):367-71 .M Adolescence; Adult; Aged; Balloon Dilatation/*; Bile Duct Obstruction, Extrahepatic/ET/RA/*TH; Cholecystectomy/AE; Duodenoscopy; Female; Human; Male; Middle Age; Pancreatitis/CO; Postoperative Complications. .T Endoscopic therapy for benign bile duct strictures. .P JOURNAL ARTICLE. .W Endoscopic therapy was attempted in 25 patients with benign strictures of the bile duct. In 23 patients, treatment involved endoscopic balloon dilation of the stricture zone or balloon dilation plus endoprosthesis placement. In 22 of 25 patients (88%), there was benefit from the endoscopic treatment. In 20 of 23 patients, there was significant radiographic improvement (p less than 0.001) in the diameter of their stricture following endoscopic therapy. All patients with elevated liver enzymes demonstrated rapid improvement following treatment. There was no significant morbidity or mortality associated with endoscopic treatment of benign biliary tract strictures. Follow-up study (mean, 4 +/- 0.3 years) discloses no recurrence of symptoms or elevated enzymes indicative of recurrent strictures. The treatment of benign bile duct strictures by a combination therapy of balloon dilation and stent placement provides a safe and effective treatment modality and an alternative to operative intervention. .A Geenen DJ; Geenen JE; Hogan WJ; Schenck J; Venu RP; Johnson GK; Jackson A Jr. .I 201128 .U 90006596 .S Gastrointest Endosc 9001; 35(5):372-6 .M Adult; Aged; Aged, 80 and over; Ambulatory Surgery/*; Common Bile Duct Calculi/*SU; Common Bile Duct Diseases/*SU; Common Bile Duct Neoplasms/*SU; Comparative Study; Endoscopy; Female; Hospitalization; Human; Male; Middle Age; Oddi's Sphincter/*SU; Retrospective Studies; Vater's Ampulla/*SU. .T Endoscopic sphincterotomy in outpatients. .P JOURNAL ARTICLE. .W We retrospectively reviewed 137 cases of outpatient endoscopic sphincterotomy (ES) performed over a 4-year period in a single center and compared them with an equal number of inpatient ES. The indications for ES in outpatients as compared with inpatients were, respectively: choledocholithiasis, 60% and 70%; papillary stenosis, 35% and 15% (p less than 0.001); stent insertion, 3.6% and 14% (p less than 0.01); and ampullary tumor, 1.4% and 0.7%. Complications were noted within 2 to 4 hours of ES in 6.6% of outpatients, a rate similar to that of inpatients--7.3%. Outpatients with complications were immediately admitted and stayed in the hospital for a mean of 5 days. No delayed complications were noted and no deaths occurred. Thus, a policy whereby selected individuals undergo ES as outpatients, with hospitalization reserved only for those in whom a complication develops, is reasonable and safe. .A Podolsky I; Kortan P; Haber GB. .I 201129 .U 90006597 .S Gastrointest Endosc 9001; 35(5):377-80 .M Antacids/*TU; Cimetidine/*TU; Esophageal and Gastric Varices/ET/*TH; Esophageal Stenosis/ET/*PC; Esophagoscopy; Evaluation Studies; Fatty Alcohols/*TU; Human; Liver Diseases, Alcoholic/CO; Male; Middle Age; Random Allocation; Sclerotherapy/*/AE; Sodium Tetradecyl Sulfate/AE/*TU; Sucralfate/*TU. .T Prevention of stricture formation after endoscopic sclerotherapy of esophageal varices. .P JOURNAL ARTICLE. .W In order to evaluate the effectiveness of an intensive acid protection regimen in preventing sclerotherapy-associated esophageal strictures, 62 patients undergoing sclerotherapy were randomized to receive either acid protection (antacids, cimetidine, and sucralfate) or no acid protection. Of 31 patients (38.7%) in the no acid protection group, 12 developed a symptomatic stricture during the course of sclerotherapy compared with 3 patients (9.7%) in the group assigned to acid protection (p less than 0.01). Our study demonstrates that a vigorous acid protection regimen will help prevent symptomatic esophageal strictures associated with variceal sclerotherapy. .A Snady H; Rosman AS; Korsten MA. .I 201130 .U 90006598 .S Gastrointest Endosc 9001; 35(5):381-5 .M Adult; Double-Blind Method; Evaluation Studies; Female; Gastric Bubble/*/AE; Human; Male; Obesity, Morbid/*TH; Prospective Studies; Random Allocation. .T A double-blind, randomized, sham-controlled trial of the gastric bubble for obesity. .P JOURNAL ARTICLE. .W We investigated the effect of an endoscopically placed gastric balloon, the Garren-Edwards gastric bubble (GEGB), on weight loss in obese patients. Fifty-nine obese patients were entered into a prospective double-blind study and randomized into two groups. In one group (34 patients) the GEGB was inserted, and in the other group (25 patients) a sham insertion was done. All patients participated in a standard weight loss program consisting of dietary therapy, behavior modification, and physical exercise. The bubble was removed endoscopically after 3 months from both groups. Patients were followed for an additional 9 months after bubble removal and weight loss was monitored. Weight loss was the same in both groups at 3 months (18.7 lb vs. 17.2 lb). This was true whether determined by change in pounds, percentage of body weight, or body mass index. We concluded that the GEGB was of no added benefit as compared with sham insertion, when combined with a standard weight loss program. Because of the lack of proven efficacy and the relatively high cost, we recommend that such devices be restricted to controlled studies until significant benefits are proven. .A Hogan RB; Johnston JH; Long BW; Sones JQ; Hinton LA; Bunge J; Corrigan SA. .I 201131 .U 90006599 .S Gastrointest Endosc 9001; 35(5):386-8 .M Adult; Aged; Aged, 80 and over; Duodenal Ulcer/*CI; Female; Gastroscopy; Heparin/*AE; Human; Male; Middle Age; Peptic Ulcer Hemorrhage/*CI; Prospective Studies; Pulmonary Embolism/CO/*DT; Retrospective Studies; Stomach Ulcer/*CI; Thrombophlebitis/CO/*DT. .T Gastroduodenal ulcer incidence in patients with venous thromboembolism. .P JOURNAL ARTICLE. .W The presence of peptic ulcer disease implies a high risk of bleeding in patients on heparin therapy. We reviewed our experience with 166 consecutive patients admitted because of venous thromboembolism. Of these 166 patients, 29 were referred for upper gastrointestinal endoscopy in order to detect the presence of any lesion that might contraindicate heparin therapy. A gastric ulcer was found in 10 patients, a duodenal ulcer in 11, and gastric erosions with signs of bleeding in 3 patients. Given the unexpectedly high frequency of ulcer in these patients, an upper gastrointestinal endoscopy was routinely performed early in the course of admission in 50 consecutive patients with venous thromboembolism. A gastric ulcer was found in 5 patients (10%), a duodenal ulcer in 7 (14%), and erosions in 2. Five of these patients had an unsuspected ulcer. A case can be made for prophylactic antiulcer therapy for all patients placed on anticoagulants for venous thromboembolism. Upper gastrointestinal endoscopy is indicated in patients with ulcer symptoms, in those with a previous history of peptic ulcer disease, and perhaps, in patients developing occult blood in the stools while on treatment with anticoagulants. .A Monreal M; Boix J; Humbert P; Lafoz E; Aguado A; Rey-Joly C. .I 201132 .U 90006600 .S Gastrointest Endosc 9001; 35(5):389-93 .M Adolescence; Adult; Aged; Diagnosis, Differential; Fatty Liver/*DI/ET/PA; Female; Human; Indocyanine Green/AD/*DU; Injections, Intravenous; Male; Middle Age; Peritoneoscopy/*. .T Peritoneoscopic examination using intravenous administration of indocyanine green in the fatty liver. .P JOURNAL ARTICLE. .W Forty patients with fatty liver were studied by peritoneoscopic examination after intravenous administration of indocyanine green (ICG). Although diffuse or centrilobular steatosis was observed in both nonalcoholic and alcoholic fatty liver, periportal steatosis was seen only in alcoholic fatty liver. Vascular markings were more prominent in alcoholic fatty liver, especially in those with fibrosis, compared with nonalcoholic fatty liver. Fat was not stained with ICG. Unstained red patches, observed after ICG administration in both nonalcoholic and alcoholic fatty liver, were thought to be due to congestion in the former and to lobular inflammation as well as congestion in the latter. Acinar markings were indistinct in the fatty liver with fibrosis but became clearer after ICG administration. .A Mizuiri K; Mo K; Sugimoto M; Abei T. .I 201133 .U 90006601 .S Gastrointest Endosc 9001; 35(5):394-7 .M Adenocarcinoma/CO/*SU; Aged; Aged, 80 and over; Carcinoma, Squamous Cell/CO/*SU; Comparative Study; Deglutition Disorders/*ET/SU; Esophageal Neoplasms/CO/*SU; Esophagoscopy; Human; Laser Surgery/*; Middle Age; Palliative Treatment/*; Prospective Studies. .T Prospective comparison of contact with noncontact Nd:Yag laser therapy for palliation of esophageal carcinoma. .P JOURNAL ARTICLE. .W Twenty patients with dysphagia due to inoperable esophageal cancer were randomized to receive either contact or noncontact endoscopic laser treatment. Treatment groups were similar with respect to age, dysphagia score, and tumor dimensions. The median number of initial treatment sessions was two in both groups, and the median treatment times per session were 23 min (range, 12 to 55 min) in the contact group and 19 min (range, 5 to 28 min) in the noncontact group. Median dysphagia scores were also similar in both groups 1 month after laser treatment, and no difference was apparent in the duration of palliation. There were no patient complications attributable to laser therapy, but damage to the laser wave guide occurred in three contact sessions and two noncontact sessions. These data suggest no advantage for the contact method of endoscopic Nd:YAG laser palliation of esophageal carcinoma with respect to number of treatment sessions, relief of dysphagia, or occurrence of complications. .A Radford CM; Ahlquist DA; Gostout CJ; Viggiano TR; Balm RK; Zinsmeister AR. .I 201134 .U 90006602 .S Gastrointest Endosc 9001; 35(5):398-402 .M Adolescence; Adult; Aged; Aged, 80 and over; Biopsy/AE; Blood Coagulation/*; Female; Hemorrhage/*ET/PC; Human; Liver Diseases/DI/*ET; Male; Middle Age; Peritoneoscopy/*; Postoperative Complications/*PC; Surgical Instruments/*. .T The use of two new coagulation probes for control of hemorrhage in laparoscopic liver biopsy. .P JOURNAL ARTICLE. .W Two new prototype probes, BICAP and Heater, were assessed to determine their effectiveness in controlling post-biopsy bleeding during laparoscopy. A total of 88 patients with a wide spectrum of liver diseases were studied. Both probes were equally effective in stopping bleeding in all patients. We recommend the use of either of these devices in controlling post-biopsy bleeding. .A Jeffers LJ; McDonald TJ; Hyder S; Foust R; Reddy KR; Schiff ER. .I 201135 .U 90006606 .S Gastrointest Endosc 9001; 35(5):419-24 .M Animal; Disease Models, Animal; Dogs; Feasibility Studies; Gastroscopy/MT; Laser Surgery/*MT; Stomach/*IR; Vagotomy/*MT. .T Endoscopic gastric vagotomy: a feasibility study using laser in dogs. .P JOURNAL ARTICLE. .W The aim of this study was to explore the feasibility of an endoscopic approach to gastric vagotomy using the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser in dogs. Based on gross and histologic measurements, target zones for endoscopic vagotomy were defined with reference to mucosal side landmarks. Target zones containing the unbranched segments of the major intramural vagal branches were linear and symmetrically located anterior and posterior to the midline of the lesser curvature extending from the level of the esophagogastric junction to the proximal antral border. Because of minimal variability between dogs, this zone could be accessed endoscopically and reliably injured. Unfortunately, it was necessary to produce a nearly full thickness burn to interrupt the deep intramural vagal branches. Despite efforts to control dosimetry, delayed perforations occurred in three of four dogs. We conclude that endoscopic gastric vagotomy using the Nd:YAG laser is not feasible in the dog model because of difficulty controlling the depth of thermal injury. An endoscopic approach to vagotomy remains conceptually appealing because of the predictable location of and accessibility to a target zone. .A Radford CM; Ahlquist DA; Sarr MG; Wold LE; Zinsmeister AR; Gostout CJ. .I 201136 .U 90006607 .S Gastrointest Endosc 9001; 35(5):425-7 .M Animal; Colon/*BS/PP; Colonoscopy/MT; Disease Models, Animal; Dogs; Hydrogen-Ion Concentration; Intestine, Small/*BS/PP; Mesenteric Vascular Occlusion/*DI/PP; Pressure; Rectum/*BS/PP. .T Endoscopic tonometric assessment of intestinal perfusion in a canine model. .P JOURNAL ARTICLE. .W In an anesthetized canine model tonometric balloons were colonoscopically placed into the right colon, left colon, and rectum. A femoral arterial line was established for the measurement of blood pressure and arterial bicarbonate. Laparotomy was performed and additional balloons were placed, via enterotomies, into the duodenum, jejunum, and ileum. Baseline measurements of intramural pH were obtained, and then the origin of the superior mesenteric artery was occluded. Additional measurements in all areas were made for two 1-hour intervals. Results showed rapid and marked acidosis as demonstrated by significant (p less than 0.001) pH changes in the jejunum, ileum, and right colon. There were no significant changes in the pH in the duodenum, left colon, or rectum. Systemic arterial pH remained normal. These data demonstrate that tonometric balloons endoscopically placed into the right colon will reflect superior mesenteric artery occlusion at an early stage, and that similar information is likely to be gained by endoscopic placement of these balloons into the jejunum. .A Schonholz S; Pleatman M; Kasserman D; Ponsky J. .I 201137 .U 90006608 .S Gastrointest Endosc 9001; 35(5):428-30 .M Aged; Case Report; Colitis/*CI/PA; Endoscopy/AE; Enteritis/*CI/PA; Human; Hydrogen Peroxide/*AE; Male. .T Hydrogen peroxide enteritis: the "snow white" sign. .P JOURNAL ARTICLE. .W Hydrogen peroxide is a useful disinfectant that has achieved widespread utility in varied clinical settings. We report an epidemic of hydrogen peroxide enteritis that developed in seven patients in our gastrointestinal endoscopy unit during a 2-week period in early 1988. During endoscopy, using recently sterilized endoscopes that were flushed with 3% hydrogen peroxide after the glutaraldehyde cycle, instantaneous blanching (the "snow white" sign) and effervescence were noted on the mucosal surfaces when the water button was depressed. No patient subsequently suffered morbidity or mortality associated with this peroxide enteritis, and the biopsy specimens revealed nonspecific inflammation. The toxicity of hydrogen peroxide when used in enema form is reviewed, as well as the pathogenesis of peroxide enteritis. .A Bilotta JJ; Waye JD. .I 201138 .U 90006609 .S Gastrointest Endosc 9001; 35(5):431-4 .M Adolescence; Adult; Aged; Aged, 80 and over; Child; Embolization, Therapeutic; Esophageal and Gastric Varices/CO/*SU; Esophagoscopy/MT; Female; Gastrointestinal Hemorrhage/*ET/SU; Human; Ligation; Male; Middle Age; Retrospective Studies. .T Endoscopic variceal ligation: an alternative to sclerotherapy. .P JOURNAL ARTICLE. .W Endoscopic variceal ligation (EVL) consists of mechanical ligation and thrombosis of varices using elastic "O" rings. This study assessed the efficacy and safety of EVL as definitive therapy for bleeding esophageal varices. During a 16-month period, 68 consecutive patients with bleeding varices had EVL. Fourteen patients died from 3 to 125 (median = 12.5) days after initial EVL. Fifteen (88%) of those actively bleeding at index treatment had bleeding controlled during index hospitalization. Survivors of index hospitalization had a 37% incidence of recurrent bleeding. Thirty-five patients had varices eradicated or reduced to small size with a median of five EVL treatments. No significant treatment-related nonbleeding complications resulted from 265 EVL sessions. EVL appears to control active variceal bleeding and eradicates varices with repeat treatments. EVL results in few nonbleeding complications, and may be employed as a safe alternative to sclerotherapy. .A Stiegmann GV; Goff JS; Sun JH; Davis D; Bozdech J. .I 201139 .U 90006610 .S Gastrointest Endosc 9001; 35(5):435-7 .M Bile Duct Obstruction, Extrahepatic/*DI/RA; Common Bile Duct Diseases/*DI/RA; Endoscopy/MT; Human. .T Peroral cholangioscopy--an improved method in the diagnosis of common bile duct diseases. .P JOURNAL ARTICLE. .A Riemann JF; Kohler B; Harloff M; Weber J. .I 201140 .U 90006611 .S Gastrointest Endosc 9001; 35(5):437-9 .M Case Report; Catheterization/*MT; Cholangiopancreatography, Endoscopic Retrograde/*IS; Duodenoscopy/IS; Human; Infant; Infant, Newborn; Jaundice, Neonatal/*DI; Male. .T A new pediatric duodenoscope: successful cannulation without a cannula elevator. .P JOURNAL ARTICLE. .A Mauer K; Waye JD. .I 201141 .U 90006613 .S Gastrointest Endosc 9001; 35(5):442-3 .M Aged; Barrett Esophagus/*DT; Case Report; Drug Evaluation; Esophageal Diseases/*CI; Human; Male; Middle Age; Peptic Ulcer/*CI; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tretinoin/*AE. .T Esophageal ulceration associated with 13-cis-retinoic acid therapy in patients with Barrett's esophagus. .P JOURNAL ARTICLE. .A Fennerty B; Sampliner R; Garewal H. .I 201142 .U 90006614 .S Gastrointest Endosc 9001; 35(5):443-5 .M Adenocarcinoma/*CO; Aged; Case Report; Endoscopy; Human; Male; Palliative Treatment/*; Pancreatic Ducts/*SU; Pancreatic Neoplasms/*CO. .T Palliation of pancreatic cancer pain by endoscopic stent placement. .P JOURNAL ARTICLE. .A Harrison MA; Hamilton JW. .I 201143 .U 90006615 .S Gastrointest Endosc 9001; 35(5):445-7 .M Aged; Carcinoma/CO/*RA; Case Report; Cholangiopancreatography, Endoscopic Retrograde/*; Female; Human; Pancreatic Ducts/*AB/RA; Pancreatic Fistula/CO/*RA; Pancreatic Neoplasms/CO/*RA; Portal System/*AB/RA. .T Opacification of the portal system during ERCP: demonstration of an anomalous pancreatico-portal connection in a patient with pancreatic carcinoma. .P JOURNAL ARTICLE. .A Ben-Zvi JS; Siegel JH; Yatto R. .I 201144 .U 90006616 .S Gastrointest Endosc 9001; 35(5):447-9 .M Aged; Case Report; Duodenoscopy/AE; Emphysema/*ET; Female; Hepatoma/*SU; Human; Liver Neoplasms/*SU; Oddi's Sphincter/*SU; Postoperative Complications/*; Subcutaneous Emphysema/*ET; Vater's Ampulla/*SU. .T Subcutaneous emphysema as a complication of endoscopic sphincterotomy of the ampulla of Vater. .P JOURNAL ARTICLE. .A Tam F; Prindiville T; Wolfe B. .I 201145 .U 90006617 .S Gastrointest Endosc 9001; 35(5):449-51 .M Agranulocytosis/*CO; Carcinoma/*DI/RA; Case Report; Cecal Diseases/BL/*DI/RA; Cecal Neoplasms/*DI/RA; Colonoscopy; Diagnosis, Differential; Human; Inflammation/BL/DI; Male; Middle Age; Neutropenia/*CO. .T Neutropenic typhlitis simulating carcinoma of the cecum. .P JOURNAL ARTICLE. .A Musher DR; Amorosi EL; Gouge T; Megibow AJ; Press RA. .I 201146 .U 90006618 .S Gastrointest Endosc 9001; 35(5):451-3 .M Aged; Case Report; Deglutition Disorders/*ET; Esophageal Diseases/CO/RA/*SU; Esophagoscopy; Female; Human; Laser Surgery/*. .T Laser lysis of an esophageal web. .P JOURNAL ARTICLE. .A Krevsky B; Pusateri JP Jr. .I 201147 .U 90006619 .S Gastrointest Endosc 9001; 35(5):453-6 .M Aged; Appendix/*PA/RA; Case Report; Cecal Diseases/DI/RA; Colonoscopy; Female; Human; Male; Middle Age; Mucocele/*DI/RA; Sigmoidoscopy. .T The volcano sign of appendiceal mucocele. .P JOURNAL ARTICLE. .A Hamilton DL; Stormont JM. .I 201148 .U 90006620 .S Gastrointest Endosc 9001; 35(5):456-8 .M Aged; Aged, 80 and over; Bile Duct Obstruction, Extrahepatic/RA/*TH; Case Report; Common Bile Duct/*IN/RA; Endoscopy/AE; Human; Male; Prosthesis/*AE. .T Bile duct perforation: a complication of large caliber endoprosthesis. .P JOURNAL ARTICLE. .A Cohen ME; Goldberg RI; Barkin JS; Phillips RS. .I 201149 .U 90006621 .S Gastrointest Endosc 9001; 35(5):459-61 .M Case Report; Esophageal and Gastric Varices/CO/RA/*TH; Esophageal Perforation/*ET/RA; Esophagoscopy; Fatty Alcohols/*TU; Female; Gastrointestinal Hemorrhage/ET; Human; Liver Transplantation/*; Middle Age; Postoperative Complications/*ET; Sclerotherapy/*AE; Sodium Tetradecyl Sulfate/*TU. .T Delayed perforation of the esophagus after variceal sclerotherapy and hepatic transplantation. .P JOURNAL ARTICLE. .A Vickers CR; O'Connor HJ; Quintero GA; Aerts RJ; Elias E; Neuberger JM. .I 201150 .U 90006623 .S Gastrointest Endosc 9001; 35(5):464-6 .M Human; Physician Payment Review Commission; Reimbursement Mechanisms/*; Relative Value Scales/*; United States. .T Can value ever be relative? .P JOURNAL ARTICLE. .A Sivak MV Jr. .I 201151 .U 90006624 .S Gastrointest Endosc 9001; 35(5):466-7 .M Alcohol, Ethyl/*AE; Esophageal and Gastric Varices/*TH; Esophageal Diseases/*CI; Human; Polyethylene Glycols/*TU; Sclerosing Solutions/*TU; Sclerotherapy/AE. .T Absolute alcohol in variceal sclerosis [letter; comment] .P COMMENT; LETTER. .A Atmakuri SP; Bhargava DK; Sharma MP. .I 201152 .U 90006625 .S Gastrointest Endosc 9001; 35(5):467-8 .M Adult; Esophageal and Gastric Varices/CO/*TH; Esophagoscopy; Female; Human; Pregnancy; Pregnancy Complications, Cardiovascular/*; Sclerotherapy/*MT. .T Sclerotherapy for esophageal varices and pregnancy [letter] .P LETTER. .A Augustine P; Joseph PC. .I 201153 .U 90006626 .S Gastrointest Endosc 9001; 35(5):468 .M Colonic Diseases/*SU; Colonic Polyps/*SU; Colonoscopy; Human; Laser Surgery/*AE. .T Hazards of contact tip use of Nd:YAG laser in treatment of colonic lesions [letter; comment] .P COMMENT; LETTER. .A Fraiberg EN; Dean K; Wiedemann M. .I 201154 .U 90006627 .S Gastrointest Endosc 9001; 35(5):468-9 .M Ambulatory Surgery/*MT; Gastrostomy/*MT; Human. .T Gastrostomy button: why complicate an office procedure? [letter; comment] .P COMMENT; LETTER. .A Gauderer MW; Stellato TA. .I 201155 .U 90006628 .S Gastrointest Endosc 9001; 35(5):469-70 .M Amnesia/*CI; Diazepam/*; Gastroscopy; Human; Midazolam/*AE; Premedication/*AE. .T Midazolam/diazepam and amnesia [letter; comment] .P COMMENT; LETTER. .A Polit SA. .I 201156 .U 90006629 .S Gastrointest Endosc 9001; 35(5):470-1 .M Acquired Immunodeficiency Syndrome/*CO; Adult; Case Report; Esophageal Diseases/*ET; Human; Male; Peptic Ulcer/*ET. .T Idiopathic ulcer of the esophagus in the AIDS syndrome: a potential life-threatening complication [letter] .P LETTER. .A Pedro-Botet J; Miralles R; Sauleda J; Rubies-Prat J. .I 201157 .U 90006630 .S Gastrointest Endosc 9001; 35(5):471 .M Colonoscopy; Diarrhea/*PS; Electrolytes/*; Feces/*PS; Human; Parasite Egg Count; Polyethylene Glycols/*; Solutions. .T Golytely interferes with stool examination for ova and parasites [letter] .P LETTER. .A Burch WC Jr; Schneider RP. .I 201158 .U 90006631 .S Gastrointest Endosc 9001; 35(5):471-2 .M Case Report; Duodenal Diseases/*ET; Duodenoscopy; Duodenum/*AB; Female; Gastrointestinal Hemorrhage/*ET; Human; Middle Age. .T Upper gastrointestinal bleeding from a duodenal duplication: an unusual complication of a rare disease [letter] .P LETTER. .A Duque JJ; Strum WB; Kuster GG; Kaufmann D. .I 201159 .U 90006632 .S Gastrointest Endosc 9001; 35(5):472-3 .M Adult; Case Report; Esophageal Diseases/*DI; Esophagoscopy; Human; Male; Mucous Membrane. .T Asymptomatic mucosal bridge of the upper esophagus [letter] .P LETTER. .A Chang FY; Lai KH; Lee SD; Tsai YT. .I 201160 .U 90006633 .S Gastrointest Endosc 9001; 35(5):473-4 .M Foreign Bodies/RA/*TH; Gastroscopy; Human; Needles/*AE; Stomach/*. .T Endoscopic removal of penetrating foreign bodies from the stomach [letter] .P LETTER. .A Shemesh E; Czerniak A; Hakerem D. .I 201161 .U 90006634 .S Gastrointest Endosc 9001; 35(5):474-5 .M Case Report; Esophageal Diseases/*CI; Esophagoscopy; Female; Human; Middle Age; Sucralfate/*AE. .T Esophageal obstruction caused by sucralfate impaction [letter] .P LETTER. .A Hart RS; Levin B; Gholson CF. .I 201162 .U 90006635 .S Gastrointest Endosc 9001; 35(5):475 .M Aged; Case Report; Esophageal Spasm, Diffuse/*DI; Esophagoscopy; Human; Male. .T Esophageal "tattooing" [letter] .P LETTER. .A Jahraus TC; Knight WA Jr. .I 201163 .U 90006636 .S Gastrointest Endosc 9001; 35(5):475-6 .M Case Report; Colonoscopy/AE; Human; Male; Middle Age; Penile Prosthesis/*; Priapism/*ET. .T Colonoscopic priapism [letter] .P LETTER. .A Bilotta JJ; Goldenberg A; Waye JD. .I 201164 .U 90006637 .S Gastrointest Endosc 9001; 35(5):476 .M Balloon Dilatation/*MT; Esophageal Achalasia/*TH; Human. .T Pneumatic dilation of achalasia without the aid of fluoroscopy [letter] .P LETTER. .A Misra SP; Dwivedi M. .I 201165 .U 90006638 .S Gastrointest Endosc 9001; 35(5):476-7 .M Aged; Case Report; Esophagoscopy; Esophagus/*; Foreign Bodies/*TH; Human; Male; Surgical Instruments/*. .T Endoscopic management of esophageal meat impaction using a splay-mouth forceps [letter] .P LETTER. .A Manabe Y; Araki M; Takeda K. .I 201166 .U 90006794 .S Geriatrics 9001; 44(10):58-60, 71-2, 74 .M Aged; Aged, 80 and over; Health Policy/LJ; Human; Informed Consent/*LJ; Patient Advocacy/*LJ; Patient Participation/*LJ; Physician-Patient Relations; Physician's Practice Patterns/LJ; Policy Making; Terminal Care/*LJ; United States. .T Physicians and patients' legal rights, Part II: Rushing to judgment in terminal care? A Geriatrics panel discussion. .P JOURNAL ARTICLE. .I 201167 .U 90006795 .S Geriatrics 9001; 44(10):75, 78, 83-4 .M Adaptation, Psychological; Aged; Aged, 80 and over; Geriatrics/*; Human; Patient Compliance; Physician-Patient Relations/*. .T 'Not him again!' Thoughts on coping with irritating elderly patients. .P JOURNAL ARTICLE. .W Elderly patients are sometimes stereotyped as "crocks" and "gomers"--crotchety chronic complainers beyond help and hope. Difficult as it may be, there is a professional way to respond to patients meeting the description. .A Slocum HE. .I 201168 .U 90006796 .S Geriatrics 9001; 44(10):9, 12 .M Academies and Institutes/*; Geriatric Assessment; Geriatrics/*; Human; Malta; United Nations/*. .T A tiny island addresses a worldwide question [editorial] .P EDITORIAL. .A Butler RN. .I 201169 .U 90007408 .S Hospitals 9001; 63(19):26 .M Hospital Bed Capacity, 500 and over; Hospitals/*ST; New York; Pilot Projects; Quality Assurance, Health Care/*EC. .T NY hospitals gamble with quality incentive pool. .P JOURNAL ARTICLE. .A Koska MT. .I 201170 .U 90007409 .S Hospitals 9001; 63(19):29, 31, 33 passim .M Commerce; Data Collection; Equipment and Supplies, Hospital/*EC; Financial Management/*TD; Leasing, Property/*TD; United States. .T It's a buyer's market for equipment leasing. .P JOURNAL ARTICLE. .A Powills S. .I 201171 .U 90007410 .S Hospitals 9001; 63(19):38-43 .M Community-Institutional Relations; Data Collection; Health Facilities/*; Health Facility Closure/*; Health Services Accessibility/*; Hospital Administrators; United States. .T CEOs confront service cuts. .P JOURNAL ARTICLE. .A Larkin H. .I 201172 .U 90007412 .S Hospitals 9001; 63(19):46 .M Confidentiality; Human; Marketing of Health Services/*; Telephone/*; United States. .T New telephone technology raises privacy issues. .P JOURNAL ARTICLE. .A Droste T. .I 201173 .U 90007413 .S Hospitals 9001; 63(19):49 .M Pharmacists/*SD; Pharmacy Service, Hospital/*MA; United States. .T Innovation alleviates pharmacist shortages. .P JOURNAL ARTICLE. .A Lappa K. .I 201174 .U 90007415 .S Hospitals 9001; 63(19):56-7 .M Attitude of Health Personnel; Economics, Medical/*TD; Human; Internship and Residency/*; Professional Practice/*TD; United States. .T Paychecks and security will lure future MDs. .P JOURNAL ARTICLE. .A Koska MT. .I 201175 .U 90007416 .S Hospitals 9001; 63(19):57-8 .M Hospitals, Teaching/*LJ; Internship and Residency/*LJ; New York; Personnel Staffing and Scheduling/LJ; Work Schedule Tolerance. .T Resident work hours basis for HANYS lawsuit. .P JOURNAL ARTICLE. .A Koska MT. .I 201176 .U 90007417 .S Hospitals 9001; 63(19):61, 64 .M Advertising; Drug Industry/*; Health Maintenance Organizations/*EC; Pharmaceutical Services/*EC; Physician's Role; Referral and Consultation; United States. .T Do consumer drug ads undercut HMO gatekeepers? .P JOURNAL ARTICLE. .A Larkin H. .I 201177 .U 90007418 .S Hospitals 9001; 63(19):69-70 .M Government; Health Policy/*; United States. .T NHPF's (National Health Policy Forum) Jones brings the policymakers together [interview by Marybeth Burke] .P JOURNAL ARTICLE. .A Jones JM. .I 201178 .U 90007419 .S Hospitals 9001; 63(19):72 .M Aged; American Hospital Association; Health Services for the Aged/*SD; Hospitals/*; Human; United States. .T AHA monograph urges broader care for elderly. .P JOURNAL ARTICLE. .A Eubanks P. .I 201179 .U 90007420 .S Hospitals 9001; 63(19):74 .M Economic Competition/LJ; Hospital Administration/*LJ; Hospitals; Illinois; Marketing of Health Services/*LJ; Product Line Management/*LJ; United States; United States Federal Trade Commission; Virginia. .T Market definition key to antitrust regulations. .P JOURNAL ARTICLE. .A Solovy A. .I 201180 .U 90007421 .S Hospitals 9001; 63(19):76 .M Child; Child, Preschool; Chronic Disease; Data Collection; Home Care Services/*SD; Hospitals; Human; Infant; Information Services/*; Social Support; United States. .T GAO: home care support services falling short. .P JOURNAL ARTICLE. .A Koska MT. .I 201181 .U 90007422 .S Hospitals 9001; 63(19):77 .M Computer Systems/*UT; Data Collection; Pharmacy Service, Hospital/*TD; Statistics; United States. .T More hospitals automate their pharmacies. .P JOURNAL ARTICLE. .A Packer C. .I 201182 .U 90007423 .S Hospitals 9001; 63(19):83 .M Administrative Personnel/*SD; Data Collection; Human; Nurse Administrators/*SD; Nursing Service, Hospital/*OG; Personnel Turnover/TD; United States. .T Nurse administrator positions are tough to fill. .P JOURNAL ARTICLE. .A Droste T. .I 201183 .U 90007425 .S Hospitals 9001; 63(20):18 .M Clinical Protocols; Information Systems/*; Outcome and Process Assessment (Health Care)/*; United States. .T National data base eyed as tool to assess outcomes. .P JOURNAL ARTICLE. .A Robinson ML. .I 201184 .U 90007428 .S Hospitals 9001; 63(20):32 .M American Hospital Association; Health Services Research/*; Hospitals/*ST; Quality Assurance, Health Care/*; United States. .T Cooperation is hallmark of HRET (Hospital Research and Educational Trust) quality project. .P JOURNAL ARTICLE. .A Koska MT. .I 201185 .U 90007433 .S Hospitals 9001; 63(20):64 .M Advertising; Blacks; Minority Groups/*; Nursing Staff, Hospital/*SD; Ohio; Personnel Management; Personnel Selection/*MT. .T New recruitment efforts target minorities. .P JOURNAL ARTICLE. .A Lappa K. .I 201186 .U 90007436 .S Hospitals 9001; 63(20):77-8 .M Health Services Research; Hospital Administration; New England; Outcome and Process Assessment (Health Care)/*; Physician's Practice Patterns/*ST. .T Hospital, patient input key to quality reforms [interview by Mary T. Koska] .P JOURNAL ARTICLE. .A Wennberg JE. .I 201187 .U 90007438 .S Hospitals 9001; 63(20):82, 84 .M Baltimore; Data Collection; Hospital Design and Construction/*EC; Iowa; Oklahoma; Risk Management/*. .T Hospitals seek to take risk out of construction. .P JOURNAL ARTICLE. .A Powills S. .I 201188 .U 90007439 .S Hospitals 9001; 63(20):84 .M Data Collection; Drugs/*SD; Pharmacy Service, Hospital/*OG; Purchasing, Hospital/*SN; United States. .T Hospital survey shows trends in drug purchases. .P JOURNAL ARTICLE. .A Souhrada L. .I 201189 .U 90007440 .S Hospitals 9001; 63(20):86, 88 .M Blood Banks/*OG; Blood Transfusion, Autologous/*AE/ST; Human; Informed Consent; Risk Management/*; United States. .T Risks remain for self-donated blood transfusions. .P JOURNAL ARTICLE. .A Eubanks P. .I 201190 .U 90007441 .S Hospitals 9001; 63(20):90 .M Decision Making; Employment/*; Hospital Administrators/*LJ; United States. .T Should you hire a lawyer? The jury is still out. .P JOURNAL ARTICLE. .A Droste T. .I 201191 .U 90007442 .S Hospitals 9001; 63(20):96 .M Canada; Information Services/*; Libraries, Hospital/*; United States. .T Untapped library resources are yours for the asking. .P JOURNAL ARTICLE. .A Ben-Shir R. .I 201192 .U 90007657 .S Hypertension 9001; 14(4):396-403 .M Aldosterone/SE; Angiotensin II/*PD; Animal; Blood Pressure/DE; Dinoprostone/SE; Hypertension/*CI/PP; Male; Methoxamine/PD; Phenoxybenzamine/PD; Pressoreceptors/PH; Rats; Rats, Inbred Strains; Receptors, Adrenergic, Alpha/DE; Regression Analysis; Splanchnic Nerves/PP; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Sympathetic Nervous System/*PP; Thromboxane B2/SE; 6-Ketoprostaglandin F1 alpha/SE. .T Angiotensin-induced hypertension in the rat. Sympathetic nerve activity and prostaglandins. .P JOURNAL ARTICLE. .W To elucidate mechanisms of angiotensin II (Ang II)-related hypertension, we infused angiotensin (76 ng/min s.c.) into rats with minipumps for 10-14 days. Control rats received sham pumps. We measured blood pressure by tail-cuff, and the excretion of aldosterone and prostaglandins (PG) (PGE2, prostacyclin derivative 6kPGF1 alpha, and thromboxane [Tx] derivative TxB2). Angiotensin II increased blood pressure by 20 mm Hg by day 2 and by 90 mm Hg by day 10. Aldosterone excretion increased from 10 to 70 ng/day in Ang II rats by day 7. Urine PGE2 did not increase in angiotensin rats; however, both 6kPGF1 alpha and TxB2 excretion increased with angiotensin. Control rats had no changes in any of these parameters. A sympathetic component was tested in a separate group of angiotensin rats that received phenoxybenzamine (300 micrograms/kg/day) during angiotensin infusion; their increase in blood pressure of 40 mm Hg at 10 days was less than in those rats with angiotensin alone but more than in control rats. Phenoxybenzamine did not influence the angiotensin-induced increases in excretion of 6kPGF1 alpha or TxB2. Additional groups of conscious angiotensin and control rats were equipped with splanchnic nerve electrodes on day 14 for recording of sympathetic nerve activity. Angiotensin rats had greater basal sympathetic nerve activity than the control rats. Incremental methoxamine injections demonstrated altered baroreceptor reflex function in rats receiving angiotensin. We conclude that increased blood pressure with chronic angiotensin infusion is accompanied by increased production of aldosterone and increased sympathetic tone. The latter may be modulated by PG. .A Luft FC; Wilcox CS; Unger T; Kuhn R; Demmert G; Rohmeiss P; Ganten D; Sterzel RB. .I 201193 .U 90007659 .S Hypertension 9001; 14(4):413-20 .M Angiotensin II/PD; Animal; Argipressin/*PD; Cell Cycle/DE; Cells, Cultured; Dose-Response Relationship, Drug; Drug Synergism; DNA/ME; Hypertrophy; Muscle Proteins/ME; Muscle, Smooth, Vascular/*DE/PA; Rats; Support, U.S. Gov't, P.H.S.. .T Arginine vasopressin-induced hypertrophy of cultured rat aortic smooth muscle cells. .P JOURNAL ARTICLE. .W Recently we reported that the contractile agonist angiotensin II induces hypertrophy, not hyperplasia, in cultured rat aortic smooth muscle cells (Geisterfer AAT, Peach MJ, Owens GK: Angiotensin II induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells. Circ Res 1988;62:749-756). We have further explored the hypothesis that contractile agonists are important regulators of smooth muscle cell growth by examining the effects of another contractile agonist, arginine vasopressin, on growth of cultured rat aortic smooth muscle cells. Autoradiographic analysis as well as cell number determinations showed that arginine vasopressin (1 microM) did not stimulate proliferation in cells made quiescent in a defined serum-free media nor did it augment proliferation in 0.4% fetal bovine serum. However, flow cytometric analysis of cellular protein content demonstrated that arginine vasopressin (1 microM) did induce cellular hypertrophy in quiescent cultures after 4 days of treatment, increasing smooth muscle cell protein content by 35% as compared with vehicle-treated controls. The increase in protein content showed a concentration dependence. Cellular hypertrophy was accompanied by an increase in [35S]methionine incorporation, which was elevated 45% by 24 hours. Both the increase in [35S]methionine incorporation and the increase in protein content could be prevented by the specific arginine vasopressin receptor antagonist. [1-beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)tyrosine] arginine vasopressin. An increase in [35S]methionine incorporation was observed between 12 and 24 hours after treatment of quiescent smooth muscle cells for only 5 minutes with arginine vasopressin (1 microM). Arginine vasopressin-induced increases in [35S]methionine incorporation was increased within 6 hours after treatment. These studies show that arginine vasopressin, like angiotensin II, induces hypertrophy but not hyperplasia of cultured rat aortic smooth muscle cells. .A Geisterfer AA; Owens GK. .I 201194 .U 90007662 .S Hypertension 9001; 14(4):435-44 .M Amino Acid Sequence; Animal; Base Sequence; Blotting, Northern; Blotting, Southern; Chromogranins/*GE; Cloning, Molecular; Comparative Study; DNA/GE; Gene Library; Genes, Structural; Molecular Sequence Data; Nerve Tissue Proteins/*GE; Oligonucleotide Probes; Pheochromocytoma/*GE; Polymorphism (Genetics); Protein Conformation; Rats; Restriction Mapping; RNA, Messenger/GE; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured. .T Molecular cloning of chromogranin A from rat pheochromocytoma cells. .P JOURNAL ARTICLE. .W Chromogranin A (CgA) is the major soluble protein in catecholamine storage vesicles. To gain insight into its function, we isolated CgA clones from a size-selected lambda gt10 rat pheochromocytoma complementary DNA (cDNA) library. The longest cDNA insert identified was 2.2 kb and encoded the entire 462-amino acid open reading frame of rat CgA including an 18-amino acid hydrophobic signal peptide. Comparison of rat CgA with the recently published sequences of bovine CgA and human CgA revealed regions of strong homology at the N-and COOH-termini as well as variant areas predominantly in the middle portion of the molecule. Regions highly conserved and therefore suggestive of functional importance included 1) multiple paired basic residues, which may serve as proteolytic processing signals; 2) a region homologous to porcine pancreastatin, a putative modulator of peptide hormone release; and 3) a short hydrophobic disulfide loop region near the N-terminus that may have a role in the targeting of CgA to secretory vesicles. On the other hand, lack of conservation of the membrane attachment sequence arginine-glycine-aspartic acid argues against its functional importance in CgA. In addition, the presence of a unique polyglutamine region in rat CgA points to a possible messenger RNA (mRNA) splice junction. Northern blot experiments demonstrated the presence of an approximately 2.2 kb rat CgA mRNA in a neuroendocrine distribution (adrenal, brain, pheochromocytoma cells, but not skeletal muscle, heart, or kidney). Southern blot studies were consistent with the presence of a single CgA gene within the rat pheochromocytoma cell genome. Finally, comparison of the present rat pheochromocytoma cDNA clones with those recently obtained from normal rat adrenal gland reveals minor but apparently real differences that suggest CgA microheterogeneity. .A Parmer RJ; Koop AH; Handa MT; O'Connor DT. .I 201195 .U 90007663 .S Hypertension 9001; 14(4):445-52 .M Animal; Blood Pressure; Chemoreceptors/PH; Denervation; Hydrostatic Pressure; Hypertension, Renovascular/*PP; Ischemia; Kidney/BS/*IR/PP; Mechanoreceptors/PH; Natriuresis; Rats; Rats, Inbred Strains; Reflex/PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Sympathetic Nervous System/PP; Ureter/PP. .T Impaired renorenal reflexes in two-kidney, one clip hypertensive rats. .P JOURNAL ARTICLE. .W In normotensive rats, stimulation of renal mechanoreceptors by an increase in ureteral pressure results in a contralateral inhibitory renorenal reflex response with contralateral natriuresis. Similar effects are produced by stimulation of renal chemoreceptors by renal pelvic perfusion with 0.9 M NaCl. However, in spontaneously hypertensive rats the renorenal reflex responses to renal mechanoreceptor and chemoreceptor stimulation are impaired. The present study was performed to examine whether the renorenal reflexes were altered in two-kidney, one clip hypertensive rats, a model of hypertension in which it has been suggested that the afferent renal nerves contribute to the enhanced peripheral sympathetic nervous activity. A 0.2 mm silver clip was placed around one renal artery 4 weeks before the study. At the time of study, mean arterial pressure was 156 +/- 4 mm Hg. Renal mechanoreceptor and chemoreceptor stimulation of either the nonclipped or clipped kidney failed to affect ipsilateral afferent renal nerve activity, contralateral efferent renal nerve activity, and contralateral urine flow rate and urinary sodium excretion. Renal denervation of the nonclipped kidney increased ipsilateral urinary sodium excretion from 0.65 +/- 0.13 to 1.50 +/- 0.42 mumol/min/g and decreased contralateral urinary sodium excretion from 0.18 +/- 0.03 to 0.13 +/- 0.03 mumol/min/g (p less than 0.05). Thus, denervation of the nonclipped kidney resulted in a similar contralateral excitatory renorenal reflex response as in normotensive rats. However, denervation of the clipped kidney increased both ipsilateral and contralateral urinary sodium excretion, from 0.14 +/- 0.04 to 0.27 +/- 0.5 mumol/min/g and from 1.29 +/- 0.33 to 2.09 +/- 0.59 mumol/min/g (p less than 0.01), respectively. Taken together these data suggest that the lack of inhibitory renorenal reflexes from the clipped kidney may enhance efferent sympathetic nervous activity and thereby contribute to the hypertension in two-kidney, one clip hypertensive rats. .A Kopp UC; Buckley-Bleiler RL. .I 201196 .U 90007665 .S Hypertension 9001; 14(4):458-9 .M Antihypertensive Agents/*; Drug Industry/*; Human; International Cooperation; Patents; United States; United States Food and Drug Administration. .T A proposal for multinational development of new drugs. .P JOURNAL ARTICLE. .A Frohlich ED. .I 201197 .U 90008140 .S Headache 9001; 29(8):498-501 .M Adolescence; Adult; Calcium Channel Blockers/*PD; Dinoprostone/*AN; Female; Human; Male; Middle Age; Migraine/*DT/ET; Nicardipine/*TU; Saliva/*AN; Thromboxane A2/*AN. .T Increase in PGE2 and TXA2 in the saliva of common migraine patients. Action of calcium channel blockers. .P JOURNAL ARTICLE. .W PGE2 and TXA2 levels and their modulation by nicardipine, a calcium blocking agent, have been studied in patients suffering from migraine. The levels of both metabolites were determined in saliva obtained during the migraine attacks, during the intervals between attacks, and after 2 months of treatment with nicardipine (20 mg every 8 h.) or placebo. The therapeutic response was evaluated on the basis of the number of migraine attacks. The results show a significant increase in the levels of both eicosanoids during the migraine attacks. In contrast to the placebo group, the number of migraine attacks and the levels of both arachidonic acid metabolites are markedly lower in the nicardipine group. Our results suggest calcium entry into the cytosol as an explanation for the increase in PGE2 and TXA2. Nicardipine interferes with calcium mobilization, thereby inhibiting arachidonic acid metabolite synthesis. .A Tuca JO; Planas JM; Parellada PP. .I 201198 .U 90008141 .S Headache 9001; 29(8):502-6 .M Adult; Aged; Case Report; Facial Injuries/*CO; Female; Forehead/*IN; Headache/*ET; Human; Male. .T Site of injury headache. .P JOURNAL ARTICLE. .W Wolff described three types of post-traumatic headaches (PTH). In type II PTH, the pain is located at the site of injury. Local soft tissue trauma and direct damage or entrapment of sensory nerves in the scar tissue are thought to be responsible for this type of headache. It is often difficult to study the neurological and autonomic changes in the scalp in these patients. We report here 8 patients with PTH in whom the site of injury was on the face thereby allowing us to evaluate the local neurological changes with greater accuracy. The results of this study corroborate Wolff's view of the pathogenesis of type II or "site of injury" PTH. .A Vijayan N; Watson C. .I 201199 .U 90008143 .S Headache 9001; 29(8):510-4 .M Adult; Caffeine/*AE; Ergotamine/*AE; Female; Headache/*CI; Human; Male; Middle Age; Prognosis; Pyrazoles/*AE; Substance Withdrawal Syndrome/*ET; Time Factors. .T Longterm prognosis of analgesic withdrawal in patients with drug-induced headaches. .P JOURNAL ARTICLE. .W We studied long-term prognosis and prognostic variables for therapeutic outcome of analgesic withdrawal in 54 patients with drug-induced headaches. The duration of headache history was 21.9 +/- 12.8 years. Each patient took an average of 38.8 +/- 22.8 tablets or suppositories a week and an average of 2.5 distinct drugs. Most patients used drugs containing several components. Caffeine was contained in at least one drug in all cases, ergotamine in 80.0% and pyrazolone in 77.1%. All patients were admitted to the hospital for two weeks. The analgesics were discontinued abruptly and the withdrawal symptoms were alleviated by neuroleptics and neurotropics. During the second week of hospital stay we started a basic therapy with calcium antagonists or beta blockers in patients suffering from migraine initially and with tricyclic antidepressants, physical therapy or biofeedback in patients suffering from tension type headaches initially. At the end of the study (mean follow-up period = 16.8 +/- 13.6 months) 38 patients (70.1%) were evaluated. 76.3% of these patients had significantly reduced their analgesic intake, 60.5% had experienced a significant relief of headache both in intensity and frequency, and 23.7% were therapeutic failures. Analysis of the time course of relapse revealed the first six months after hospital discharge as the critical period determining long-term success. The variables tested for prognostic relevance (age, sex, duration of headache history, number of tablets or suppositories taken a week, organic mental syndrome, and type of initial headaches) were not statistically significant. .A Baumgartner C; Wessely P; Bingol C; Maly J; Holzner F. .I 201200 .U 90008145 .S Headache 9001; 29(8):517-8 .M Adult; Aged; Aged, 80 and over; Female; Human; Male; Mexiletine/*TU; Middle Age; Trigeminal Neuralgia/*DT. .T Failure of mexiletine to control trigeminal neuralgia. .P JOURNAL ARTICLE. .W The analgesic effects of lidocaine and tocainide on trigeminal neuralgia have been established. However, both drugs are unpractical: lidocaine can only be used intravenously, and tocainide may exhibit serious haematological side effects. Mexiletine, a structural analogue of lidocaine that can be safely administered by the oral route, was given, as the sole drug, to four patients with active trigeminal neuralgia. After at least seven days on mexiletine they had no clear benefit. The four patients subsequently improved with carbamazepine or phenytoin. Our observations suggest that mexiletine alone is not of value in trigeminal neuralgia. .A Pascual J; Berciano J. .I 201201 .U 90008146 .S Headache 9001; 29(8):519-22 .M Aged; Female; Headache/*ET; Human; Iohexol/*AE; Iopamidol/*AE; Male; Middle Age; Myelography/*AE; Prospective Studies; Support, U.S. Gov't, P.H.S.. .T Adverse reactions to iopamidol and iohexol myelography with special attention to headache: role of myelographic technique. .P JOURNAL ARTICLE. .W In order to identify those myelographic risk factors associated with a higher incidence of adverse effects, myelographic technique, patient variables and post-myelographic symptoms were prospectively recorded in a group of 152 patients studied with iopamidol and in a second group of 28 patients studied with iohexol. None of the technical factors studied were identified to have a statistically significant relationship with the incidence of adverse reactions. Older patients fared better than younger patients in both groups. Overall, there was a lower incidence of side effects in the iopamidol group (29%) than in the iohexol group (50%). Headache, nausea, and vomiting were the most frequent reactions seen. .A Sobel DF; Rowe R; Zyroff J; Koziol JA; Frost F; Krupsaw J. .I 201202 .U 90008147 .S Headache 9001; 29(8):523-7 .M Asthenopia/*CO; Chronic Disease; Female; Headache/*CO; Human; Light; Male; Middle Age; Time Factors; Vision Disorders/*CO/EP. .T A controlled study of visual symptoms and eye strain factors in chronic headache. .P JOURNAL ARTICLE. .W In a questionnaire survey we determined the prevalence of visual symptoms and eye strain factors in a group of chronic headache sufferers as compared with age- and sex-matched controls. The visual symptoms studied were those not specific for headache, i.e., sensitivity to light and blurred vision. Sensitivity to light in the absence of headache was reported by 27.8% of controls and 44.7% of headache sufferers (p less than 0.05). The latter figure increased to 71.3% when headache was actually present (p less than 0.001). Blurred vision occurred in 13.5% of controls and 7.4% of headache sufferers (not significant). In the presence of headache, the latter figure increased to 44.7% (p less than 0.01). Of the eye strain factors studied, bright light was reported to precipitate headache in 29.3% and to aggravate it in 73.4%. For reading, these figures were 16.0% and 55.3%, respectively; for working at the computer screen, 14.5% and 31.3%; and for watching television, 6.4% and 27.7%. We conclude that visual symptoms are more common in chronic headache and eye strain factors more important than is generally recognized. .A Vincent AJ; Spierings EL; Messinger HB. .I 201203 .U 90008148 .S Headache 9001; 29(8):528-31 .M Headache/*TH; Home Nursing/*; Human; Patient Compliance; Quality of Health Care; Self Care/*. .T An analysis of home practice patterns for non-drug headache treatments. .P JOURNAL ARTICLE. .W Regular home practice of non-drug training techniques is assumed essential for improved headache control. In numerous research studies on non-drug treatment efficacy, subjects have been routinely required to practice daily self-regulation techniques. This paper examines the relationship between amount of home practice and treatment outcome, and the extent to which subjects adhere to training requirements. A total of 42 subjects completed daily home practice records for 32 weeks. Fourteen subjects had randomly been assigned to an autogenic phases group, 17 to an electromyographic biofeedback group, and 11 to a thermal training group. All subjects charted frequency of practice, change of feeling in the target area, time required to bring about the change, and general body relaxation. Relationships between subject compliance and 11 selected variables including demographics, headache activity components, treatment group, and treatment outcome were evaluated. Results support home practice, but place greater emphasis on its quality rather than its quantity. .A Solbach P; Sargent J; Coyne L. .I 201204 .U 90008497 .S J Appl Physiol 9001; 67(2):523-7 .M Adult; Anoxia/PP; Blood Pressure; Comparative Study; Heart/*PH; Heart Rate/DE; Hemodynamics; Human; Isoproterenol/*PD; Male; Norepinephrine/BL; Oxygen Consumption/*; Support, Non-U.S. Gov't; Time Factors. .T Reversal of hypoxia-induced decrease in human cardiac response to isoproterenol infusion. .P JOURNAL ARTICLE. .W A decrease in heart rate response to isoproterenol (IP) infusion has been previously described in humans exposed to acute (2-3 days) or chronic (21 days) exposure to altitude hypoxia (J. Appl. Physiol. 65: 1957-1961, 1988). To evaluate this cardiac response in subacute (8 days) hypoxia and to explore its reversal with restoration of normoxia, six subjects received an IP infusion under normoxia (condition N), after 8 days in altitude (4,350 m, condition H8), on the same day in altitude after inhalation of O2 restoring normoxic arterial O2 saturation (SaO2, condition HO), and 6-11 h (condition RN) and 4-5 mo (condition ND) after the return to sea level. Cardiac chronotropic response to IP, evaluated by the mean increase in heart rate from base value (delta HR, min-1), was lower in condition H8 [mean 30 +/- 13 (SD)] than in condition N (50 +/- 14, P less than 0.03); it was slightly higher in condition HO (38 +/- 14) or condition RN (42 +/- 15) than condition H8 but still significantly different from condition N (P less than 0.03), despite normal values of SaO2. delta HR in condition ND (55 +/- 10) returned to base N value. These findings confirm the hypothesis of a hypoxia-induced decrease in cardiac chronotropic function. Two possible mechanisms are suggested: an O2-dependent one, rapidly reversible with recent restoration of normoxia, and a more slowly reversible mechanism, probably a downregulation of the cardiac beta-receptors. .A Richalet JP; Le-Trong JL; Rathat C; Merlet P; Bouissou P; Keromes A; Veyrac P. .I 201205 .U 90008498 .S J Appl Physiol 9001; 67(2):528-33 .M Animal; Blood Pressure; Cardiac Output; Comparative Study; Dogs; Female; Fixatives; Heart Rate; Hemodynamics; Male; Oxygen Consumption/*; Pulmonary Alveoli/*ME; Pulmonary Edema/*ET/PA; Pulmonary Gas Exchange; Reperfusion Injury/*CO; Support, U.S. Gov't, P.H.S.; Time Factors. .T Lack of alveolar O2 during lung reperfusion does not decrease edema formation. .P JOURNAL ARTICLE. .W We previously reported that pulmonary arterial occlusion for 48 h followed by 4 h of reperfusion in awake dogs results in marked edema and inflammatory infiltrates in both reperfused and contralateral lungs (Am. Rev. Respir. Dis. 134: 752-756, 1986; J. Appl. Physiol. 63: 942-950, 1987). In this experiment we study the effects of alveolar hypoxia on this injury. Anesthetized dogs underwent thoracotomy and occlusion of the left pulmonary artery. Twenty-four hours later the dogs were reanesthetized, and a double-lumen endotracheal tube was placed. The right lung was continuously ventilated with an inspiratory O2 fraction (FIO2) of 0.35. In seven study animals the left lung was ventilated with an FIO2 of 0 for 3 h after the left pulmonary artery occluder was removed. In six control animals the left lung was ventilated with an FIO2 of 0.35 during the same reperfusion period. Postmortem bloodless wet-to-dry weight ratios were 5.87 +/- 0.20 for the left lower lobe and 5.32 +/- 0.12 for the right lower lobe in the dogs with hypoxic ventilation (P less than 0.05 for right vs. left lobes). These values were not significantly different from the control dog lung values of 5.94 +/- 0.22 for the left lower lobe and 5.11 +/- 0.07 for the right lower lobe (P less than 0.05 for right vs. left lobes). All values were significantly higher than our laboratory normal of 4.71 +/- 0.06. We conclude that reperfusion injury is unaffected by alveolar hypoxia during the reperfusion phase. .A Overand PT; Bishop MJ; Eisenstein BL; Chi EY; Su M; Cheney FW. .I 201206 .U 90008499 .S J Appl Physiol 9001; 67(2):534-40 .M Animal; Horses/*PH; Oxygen Consumption; Physical Conditioning, Animal; Pressure; Pulmonary Wedge Pressure; Respiration; Respiratory System/*PH; Support, Non-U.S. Gov't. .T Inertance of the respiratory system in ponies. .P JOURNAL ARTICLE. .W The purpose of the present work was to measure the pulmonary inertance (IL) in ponies and to analyze its potential influence on the mechanics of breathing and on their aptitude to increase ventilation during exercise. Five healthy ponies 2.4-4 yr old [mean wt 255 +/- 15 (SE) kg] were used. On the one hand, inertance of the respiratory system (Irs) was computed from the value of the resonant frequency (fr) measured by the forced oscillation technique. On the other hand, respiratory airflow, tidal volume (VT), and transpulmonary pressure (PL) changes were recorded while the ponies were performing a light treadmill exercise, and IL was calculated as the ratio of the associated differences in inertial pressure (delta Pin) to volume acceleration (delta V). Respiratory airflow and VT were measured with a Fleisch pneumotachograph (no. 5) and PL with an intraesophageal balloon catheter. First, the protocol was carried out with the ponies breathing air and He-O2, second, while the ponies breathed through two additional tubes (100 cm long, 3 cm ID), then one, and finally none, fixed on the Fleisch pneumotachograph. Finally, the contribution of the extra- vs. the intrathoracic airways to IL was estimated by measuring the lateral midtracheal pressure recorded simultaneously with the aforementioned parameters. The values of Irs calculated with fr and of IL calculated on the basis of the delta Pin-delta V ratio were 29.8 +/- 0.4 and 19.8 +/- 1.0.10(-4) kPa.l-1.s-2, respectively. During He-O2 breathing IL decreased about three times; this result was similar to the predicted decrease based on gas density only.(ABSTRACT TRUNCATED AT 250 WORDS) .A Art T; Lekeux P; Gustin P; Desmecht D; Amory H; Paiva M. .I 201207 .U 90008500 .S J Appl Physiol 9001; 67(2):541-6 .M Adenosine/*PH; Aminophylline/PD; Animal; Blood Pressure; Comparative Study; Dipyridamole/PD; Oxygen Consumption/*; Rabbits; Respiration/*/*DE; Respiratory System/ME; Support, Non-U.S. Gov't; Time Factors. .T Role of adenosine in hypoxic ventilatory depression. .P JOURNAL ARTICLE. .W The role of adenosine in the ventilatory depression induced by hypoxia was studied in 82 spontaneously breathing urethan-anesthetized 4-day-old rabbit pups. Respiration was monitored with a pneumotachograph. The animals were exposed to hypoxia (6% O2 in N2) for 30 min or until the occurrence of terminal apnea. In all animals hypoxia produced an initial increase in ventilation followed by a decrease. In the control group 52% of the animals became apneic after 7 min of hypoxic exposure. By contrast, pretreatment with dipyridamole (10 or 20 mg/kg), an adenosine uptake blocker, significantly shortened the time needed to reach apnea. Thus at 7 min of hypoxia 93% of the animals that received dipyridamole became apneic. On the other hand, administration of adenosine antagonists 8-p-sulfophenyltheophylline (5 or 8 mg/kg) and aminophylline (10 or 25 mg/kg) significantly prolonged the time required to produce apnea. Only 20% of the animals that received these antagonists became apneic at 7 min of hypoxia. These results suggest that adenosine is potentially involved in the ventilatory depression produced by hypoxia in neonatal rabbit pups. .A Runold M; Lagercrantz H; Prabhakar NR; Fredholm BB. .I 201208 .U 90008501 .S J Appl Physiol 9001; 67(2):547-55 .M Adult; Comparative Study; Exercise Test; Exertion/*; Female; Human; Lactates/BL; Male; Models, Biological; Oxygen Consumption; Pulmonary Gas Exchange/*; Respiration; Respiratory System/PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Influence of work rate on ventilatory and gas exchange kinetics. .P JOURNAL ARTICLE. .W A linear system has the property that the kinetics of response do not depend on the stimulus amplitude. We sought to determine whether the responses of O2 uptake (VO2), CO2 output (VCO2), and ventilation (VE) in the transition between loadless pedaling and higher work rates are linear in this respect. Four healthy subjects performed a total of 158 cycle ergometer tests in which 10 min of exercise followed unloaded pedaling. Each subject performed three to nine tests at each of seven work rates, spaced evenly below the maximum the subject could sustain. VO2, VCO2, and VE were measured breath by breath, and studies at the same work rate were time aligned and averaged. Computerized nonlinear regression techniques were used to fit a single exponential and two more complex expressions to each response time course. End-exercise blood lactate was determined at each work rate. Both VE and VO2 kinetics were markedly slower at work rates associated with sustained blood lactate elevations. A tendency was also detected for VO2 (but not VE) kinetics to be slower as work rate increased for exercise intensities not associated with lactic acidosis (P less than 0.01). VO2 kinetics at high work rates were well characterized by the addition of a slower exponential component to the faster component, which was seen at lower work rates. In contrast, VCO2 kinetics did not slow at the higher exercise intensities; this may be the result of the coincident influence of several sources of CO2 related to lactic acidosis. These findings provide guidance for interpretation of ventilatory and gas exchange kinetics. .A Casaburi R; Barstow TJ; Robinson T; Wasserman K. .I 201209 .U 90008502 .S J Appl Physiol 9001; 67(2):556-62 .M Animal; Cattle; Cells, Cultured; Comparative Study; Diglycerides; Dose-Response Relationship, Drug; Endothelium, Vascular/*PH; Hydrogen Peroxide/AN; Immune Adherence Reaction; Ionomycin/PD; Monocytes/*PH; Neutrophils/*PH; Phorbol 12,13-Dibutyrate/PD; Phorbols/PD; Protein Kinase C/*ME; Second Messenger Systems/*DE; Superoxide/AN; Support, Non-U.S. Gov't. .T Contrasting effects of inflammatory stimuli on neutrophil and monocyte adherence to endothelial cells. .P JOURNAL ARTICLE. .W Leukocyte adherence to endothelial cells (EC) is an important early event in inflammatory responses, which are often characterized by a predominance of either neutrophils (PMN) or monocytes. However, there is little information concerning the molecular events important in leukocyte adherence to EC. Intracellular activation of protein kinase C and the calcium-second messenger system leads to the stimulation of a number of important functions in PMN and monocytes. We compared the effects of members of these pathways on human PMN and monocyte adherence to cultured bovine aortic EC. We observed that phorbol myristate acetate, phorbol, 12,13-dibutyrate, L-alpha-1-oleoyl-2-acetoyl-sn-3-glycerol, and ionomycin each induced significant dose-dependent increases in PMN adherence to EC monolayers. In contrast, similar concentrations of each of these agents induced significant decreases in EC adherence of monocytes enriched by countercurrent centrifugal elutriation. Separate experiments determined that the differences in PMN and monocyte adherence to EC were not related to differences in oxidant production because 1) phorbol myristate acetate and L-alpha-1-oleoyl-2-acetoyl-sn-3-glycerol caused similar marked increases in both PMN and monocyte superoxide anion and hydrogen peroxide production and 2) ionomycin, which had opposing effects on PMN and monocyte adherence, had no effect on PMN and monocyte superoxide anion or hydrogen peroxide release. We conclude that activators of protein kinase C and the Ca-second messenger pathway have opposite effects on PMN and monocyte adherence to EC and that these effects are mediated by O2 radical-independent mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS) .A Kamp DW; Bauer KD; Knap A; Dunn MM. .I 201210 .U 90008503 .S J Appl Physiol 9001; 67(2):563-9 .M Acid-Base Equilibrium; Acidosis, Respiratory/*CF; Animal; Bicarbonates/AN; Blood Chemical Analysis; Blood Pressure; Chlorides/AN; Comparative Study; Dogs; Electrolytes/*ME; Furosemide/*PD; Hematocrit; Hydrogen-Ion Concentration; Lactates/BL; Potassium/AN; Sodium/AN; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Time Factors. .T Furosemide and cerebrospinal fluid ions during acute respiratory acidosis. .P JOURNAL ARTICLE. .W The purpose of this study was to investigate the effects of furosemide, an inhibitor of NaCl cotransport, on cisternal cerebrospinal fluid (CSF) acid-base balance during acute respiratory acidosis (ARA). We measured blood and CSF acid-base variables in two groups (n = 7 in each) of anesthetized, paralyzed, and mechanically ventilated dogs with bilateral ligation of renal pedicles (to eliminate saluresis). After base-line samples were obtained (-1 h), furosemide (50 mg/kg) was administered intravenously within 15 min (group II); group I received an equal volume of half-normal saline. ARA was induced 1 h later (0 h) and arterial CO2 tension was maintained between 55 and 60 Torr for 5 h. Mean cisternal CSF PCO2 was 42.8 +/- 2.6 and 39.5 +/- 1.7 Torr, respectively in groups I and II and rose approximately 20 Torr during ARA. In group I, CSF [HCO3-] was 22.0 +/- 1.0, 24.8 +/- 0.6, and 25.4 +/- 1.6 meq/l, respectively at 0, 2.5, and 5 h. Respective values for group II were 22.2 +/- 1.3, 24.3 +/- 1.8, and 24.6 +/- 1.0 meq/l. These values were not significantly different from each other. In each group, CSF [Na+-Cl-] increased significantly during ARA, but the changes were not significantly different when the two groups were compared. We conclude that furosemide at the dose used in the present study does not change ionic composition and acid-base balance of cisternal CSF compared with control. Because changes in CSF [Na+-Cl-] during ARA were similar in both groups, any inhibition of Cl- influx into CSF by furosemide should have been proportional to that of Na+. .A Javaheri S; Freidel JF; Davis PJ. .I 201211 .U 90008504 .S J Appl Physiol 9001; 67(2):570-7 .M Animal; Biopsy; Citrate Synthase/AN; Comparative Study; Exertion/*; Female; Glycogen/ME; Horses/*PH; Lactate Dehydrogenase/AN; Lactates/BL; Muscles/EN/*PH; Physical Conditioning, Animal/*; Support, Non-U.S. Gov't; Time Factors; 3-Hydroxyacyl CoA Dehydrogenases/AN. .T Effects of a draft-loaded interval-training program on skeletal muscle in the horse. .P JOURNAL ARTICLE. .W Five Standardbred trotters were trained on a treadmill 3 times/wk for 12 wk by intervals of draft-loaded exercise. The draft load was 34 kp and the velocity approximately 7 m/s. Muscle biopsies were taken from the gluteus medius and longissimus muscles before training and after 2, 4, 8, and 12 wk of training and from the brachiocephalicus muscle before and after training. Both the percentage and the area of type IIa fibers increased and the percentage of type IIb fibers decreased in the gluteus medius muscle during the first 2 wk of training, and then no further significant difference was noted. The percentage of type I fibers increased in the brachiocephalicus muscle, and the area of type IIb fibers increased in the longissimus muscle. The citrate synthase activity increased in the gluteus muscle only, and the increase was seen during the first 2 wk. No significant differences were seen in 3-hydroxy-acyl-CoA dehydrogenase and lactate dehydrogenase activities in the muscles during the entire training period. Less glycogen was utilized in the gluteus muscle and less blood lactate accumulated when the horses performed an unloaded submaximal exercise test after compared with before training. It can be concluded that rapid changes are induced in the gluteus medius muscle when horses are trained pulling a light-draft resistance at a submaximal trotting speed. .A Gottlieb M; Essen-Gustavsson B; Lindholm A; Persson SG. .I 201212 .U 90008505 .S J Appl Physiol 9001; 67(2):578-83 .M Animal; Body Temperature Regulation/*; Carotid Body/*PH; Cats; Chemoreceptors/PH; Comparative Study; Denervation; Oxygen Consumption/*; Plethysmography; Respiration; Support, Non-U.S. Gov't. .T Effects of hypoxia on thermal polypnea in intact and carotid body-denervated conscious cats. .P JOURNAL ARTICLE. .W The effects of the level of oxygenation on the respiratory response to heat exposure have been studied in conscious cats during normoxia, severe or mild hypocapnic hypoxia [inspired O2 fraction (FIO2) = 0.11 or 0.13], or hyperoxia. Several cats were also studied during severe normocapnic hypoxia. Experiments were repeated while the same animals were chronically carotid body denervated (CBD). The increase in respiratory frequency (f) leading to thermal tachypnea occurred at a lower body temperature (Tb) in severe hypocapnic hypoxia than in ambient air, but this effect was less pronounced when hypocapnia was corrected. No significant changes were observed during mild hypoxia or hyperoxia compared with normoxia in intact animals. After CBD, thermal tachypnea occurred at lower Tb in air than it did with intact animals in three of five cats, and it also occurred at lower Tb in mild hypocapnic hypoxia compared with air. It appears, therefore, that in conscious cats exposed to heat load 1) severe hypoxia enhances thermal tachypnea, 2) this effect persists after CBD, which suggests that it originates from a central action of hypoxia, and 3) the chemoreceptor afferents, to some degree, inhibit the onset of thermal tachypnea, as was previously observed for hypoxic tachypnea, which appears only in CBD cats (J. Appl. Physiol. 49: 769-777, 1980). Therefore, triggering of thermal and hypoxic tachypnea may involve common central mechanisms, probably located in the diencephalic structures under the control of afferents from arterial chemoreceptors. .A Bonora M; Gautier H. .I 201213 .U 90008506 .S J Appl Physiol 9001; 67(2):584-91 .M Animal; Comparative Study; Electrophysiology; Male; Membrane Potentials; Methysergide/ME; Nerve Fibers/PH; Nodose Ganglion/*ME; Rabbits; Serotonin/*PD; Support, U.S. Gov't, P.H.S.; Tubocurarine/ME; Vagus Nerve/*ME. .T Serotonin increases excitability of rabbit C-fiber neurons by two distinct mechanisms. .P JOURNAL ARTICLE. .W Serotonin (5-HT) increases impulse activity in visceral afferent C-fibers in vivo. A 5-HT-induced membrane depolarization may partially account for this effect. Here, we examined the potential contribution of an additional mechanism to the 5-HT-mediated increase in impulse activity. Approximately 40% of rabbit visceral C-fiber neurons exhibit a protracted (greater than 3 s) spike afterhyperpolarization (AHPslow) that is a major determinant of repetitive firing properties in these neurons. Intracellular recording methods were applied to rabbit nodose ganglion neurons in vitro to assess whether 5-HT could increase excitability through effects on the AHPslow. Results revealed a concentration-dependent 5-HT-mediated depression of the AHPslow amplitude and duration that was accompanied by decreased accommodation of action potential firing. Experiments with 5-HT receptor antagonists further showed that this autacoid depressed the AHPslow through a different 5-HT receptor subtype than that subserving the 5-HT-induced depolarization. Thus the AHPslow represents a distinct locus where 5-HT can increase the impulse activity of these visceral C-fiber afferents. .A Christian EP; Taylor GE; Weinreich D. .I 201214 .U 90008507 .S J Appl Physiol 9001; 67(2):592-8 .M Adenosine Triphosphatase/ME; Adolescence; Adult; Biopsy; Capillaries/AN; Comparative Study; Human; Intercostal Muscles/*AN/BS; Male; Middle Age; Periodic Acid-Schiff Reaction; Respiratory Muscles/*AN/BS; Support, Non-U.S. Gov't. .T Histochemical characteristics of human expiratory and inspiratory intercostal muscles. .P JOURNAL ARTICLE. .W The relative occurrence of slow-twitch (ST) and fast-twitch (FTa and FTb) fibers, fiber size, and capillary supply in internal (INT) and external intercostal muscles (EXT), the costal diaphragm (DIA), and vastus lateralis muscle (VAS) was examined post-mortem in eight healthy males. The relative occurrence of ST fibers in INT [64 +/- 3% (SE)] and EXT (62 +/- 3%) was similar but higher than in DIA (49 +/- 3%) and VAS (40 +/- 6%; P less than 0.05). The occurrence of FTa fibers in expiratory INT (35 +/- 3%) was higher than in inspiratory INT and EXT (17 +/- 1%; P less than 0.05) but similar to DIA (28 +/- 6%) and VAS (32 +/- 2%). Accordingly, expiratory INT had fewer FTb fibers (1 +/- 1%) than the others (P less than 0.05). Expiratory INT had a 60% larger fiber area than inspiratory INT and EXT and DIA (P less than 0.05), but the area was similar to that of VAS. The number of capillaries per fiber was higher in expiratory INT (2.3 +/- 0.1) than in inspiratory INT and EXT (1.6 +/- 0.1), DIA (1.9 +/- 0.1), and VAS (1.8 +/- 0.2; P less than 0.05). The results suggest that the occurrence of many large capillary-rich FTa fibers in expiratory INT is bound to function (expiratory vs. inspiratory) rather than to anatomy (INT vs. EXT). .A Mizuno M; Secher NH. .I 201215 .U 90008508 .S J Appl Physiol 9001; 67(2):599-605 .M Anesthesia, General; Animal; Comparative Study; Diaphragm/PH; Dogs; Electromyography; Female; Laparotomy/*; Oxygen Consumption; Posture; Respiration; Respiratory Airflow; Respiratory Muscles/*PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Effects of midline laparotomy on expiratory muscle activation in anesthetized dogs. .P JOURNAL ARTICLE. .W Abdominal surgery has a marked inhibitory influence on the diaphragm, but its effect on the expiratory muscles is not known. Therefore, we have recorded the electromyograms of the triangularis sterni, abdominal external oblique, and transversus abdominis before and after a midline laparotomy in 10 anesthetized, spontaneously breathing dogs. Measurements were obtained during quiet breathing in the supine posture, during breathing against expiratory threshold loads, during head-up tilting, and during hyperoxic hypercapnia. Expiratory activation of the transversus abdominis in all conditions was considerably reduced after laparotomy. This reduction was real, as no change in the compound muscle action potential during single pulse stimulation was observed. In contrast, expiratory recruitment of either the triangularis sterni or the abdominal external oblique was maintained or increased. We therefore conclude that laparotomy inhibits not only activation of the diaphragm during inspiration but also activation of the transversus abdominis during expiration. Visceral afferents thus affect in concert the two respiratory muscles lining the peritoneum. The present findings also emphasize the important fact that the pattern of activation of a particular abdominal muscle is not necessarily representative of the entire abdominal musculature. .A Farkas GA; De Troyer A. .I 201216 .U 90008509 .S J Appl Physiol 9001; 67(2):606-13 .M Albumins/*PK; Animal; Comparative Study; Dextrans/*PK; Hyaluronidase/*PK; Lung/*ME; Permeability; Rabbits; Sodium Chloride/ME; Support, U.S. Gov't, P.H.S.; Viscosity. .T Effects of albumin, dextran, and hyaluronidase on pulmonary interstitial conductivity. .P JOURNAL ARTICLE. .W The fluid conductivity of albumin solutions of various concentrations relative to that of saline was measured in the interstitium surrounding a short segment of a large (1.5- to 3-mm-diam) blood vessel of an isolated rabbit lung of which air spaces and vasculature were filled with silicon rubber. At a constant driving pressure, the flow of the following solutions was measured sequentially: normal saline and albumin solution (3, 5.5, 8, or 15 g/100 ml saline), hyaluronidase solution (0.02 g/100 ml), and albumin solution (same concentration used before hyaluronidase solution). The albumin-to-saline flow ratios averaged 1.00 +/- 0.23 (SD), 1.01 +/- 0.21, 1.32 +/- 0.63, and 1.54 +/- 0.36 for albumin concentrations of 3, 5.5, 8, and 15 g/100 ml, respectively. These ratios were higher than the corresponding values of 0.88, 0.78, 0.72, and 0.5 expected if the flow of albumin solution were to depend only on fluid viscosity. The flow of dextran and hyaluronan solutions was more viscosity dependent than the flow of albumin solutions. The increased flow of albumin solution could be the result of a reduced excluded volume of albumin caused by collagen and glycosaminoglycans with an increased albumin concentration. The flow of hyaluronidase solution was 24 +/- 22 (SD)-fold (n = 36) larger than the flow of albumin solution. Thus hyaluronan was responsible for most of the hydraulic resistance of the interstitium to bulk flow. After its degradation, the flow of albumin solution became more viscosity dependent. The interaction between plasma proteins and glycosaminoglycans in the pulmonary interstitium could serve to enhance clearance of microvascular filtrate, particularly under conditions of large protein leaks. .A Lai-Fook SJ; Rochester NL; Brown LV. .I 201217 .U 90008510 .S J Appl Physiol 9001; 67(2):614-9 .M Animal; Bronchi/*SE; Comparative Study; Mucus/*SE; Oscillometry; Posture; Sheep; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Time Factors; Trachea/ME. .T Removal of excessive bronchial secretions by asymmetric high-frequency oscillations. .P JOURNAL ARTICLE. .W The present study evaluated whether high-frequency oscillations (HFO) with biased flow profiles applied at the airway opening are capable of altering mucus clearance. In eight anesthetized sheep, artificial mucus (100 P) was infused continuously (1 ml/min) into the left main bronchus via a cannula inserted through the dorsal wall of the left main bronchus after thoracotomy. Outcoming mucus was collected every 10 min from the end of a cuffed orotracheal tube. Animals were ventilated with a Harvard respirator at a low frequency with superimposed HFO at 14 Hz with asymmetrical waveforms generated by a digitally controlled electromagnetic piston pump (expiratory bias: peak expiratory flow 3.8 l/s, peak inspiratory flow 1.3 l/s; inspiratory bias: reverse of expiratory bias). The influence of posture and of HFO airflow bias on mucus clearance was determined. In the horizontal position, mucus clearance with expiratory biased HFO was 3.5 +/- 2 (SD) ml/10 min. Head-down tilt produced a clearance of 3.1 +/- 3 ml/10 min; addition of HFO with expiratory bias increased clearance to 11.0 +/- 2.0 ml/10 min (P less than 0.05). No clearance occurred with inspiratory biased HFO during head-down tilt. These results indicate that expiratory biased HFO at the airway opening can clear excessive airway secretions and augment clearance by postural drainage. .A Freitag L; Long WM; Kim CS; Wanner A. .I 201218 .U 90008511 .S J Appl Physiol 9001; 67(2):620-7 .M Adenosine Triphosphatase/AN; Animal; Capillaries/EN; Cats; Comparative Study; Diaphragm/*IN; Fatigue; Image Processing, Computer-Assisted; Motor Neurons/EN; Oxidation-Reduction; Periodic Acid-Schiff Reaction; Respiratory Muscles/*BS/EN; Succinate Dehydrogenase/AN; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Oxidative capacity and capillary density of diaphragm motor units. .P JOURNAL ARTICLE. .W Motor units in the cat diaphragm (DIA) were isolated in situ by microdissection and stimulation of C5 ventral root filaments. Motor units were classified based on their isometric contractile force responses and fatigue indexes (FI). The muscle fibers belonging to individual units (i.e., the muscle unit) were identified using the glycogen-depletion method. Fibers were classified as type I or II based on histochemical staining for myofibrillar adenosine triphosphatase (ATPase) after alkaline preincubation. The rate of succinate dehydrogenase (SDH) activity of each fiber was determined using a microphotometric procedure. The location of capillaries was determined from muscle cross sections stained for ATPase after acid (pH = 4.2) preincubation. The capillarity of muscle unit fibers was determined by counting the number of capillaries surrounding fibers and by calculating the number of capillaries per fiber area. A significant correlation was found between the fatigue resistance of DIA units and the mean SDH activity of muscle unit fibers. A significant correlation was also observed between DIA unit fatigue resistance and both indexes of muscle unit fiber capillarity. The mean SDH activity and mean capillary density of muscle unit fibers were also correlated. We conclude that DIA motor unit fatigue resistance depends, at least in part, on the oxidative capacity and capillary density of muscle unit fibers. .A Enad JG; Fournier M; Sieck GC. .I 201219 .U 90008512 .S J Appl Physiol 9001; 67(2):628-35 .M Animal; Capillaries/*PH; Comparative Study; Dogs; Female; Hydrostatic Pressure; In Vitro; Lung/*BS; Male; Organ Weight; Serum Albumin/ME; Support, Non-U.S. Gov't. .T Do transvascular forces in isolated lobe preparations equilibrate? .P JOURNAL ARTICLE. .W We used the stepwise pressure elevation technique to study the relationship between rate of constant weight gain (Qf) and microvascular pressure (Pc) in eight isolated canine left lower lobes. The slope of this relationship, which is assumed to represent lobar conductance to filtration (Kf) was 0.0022 +/- 0.003 ml.min-1.cmH2O-1.g dry wt-1. The intercept when Qf = 0, Pcrit, commonly interpreted as the Pc at which the balance of forces across the microvasculature is overwhelmed, was 9.53 +/- 1.18 cmH2O, a lower Pc than commonly used in weight transient experiments. Consequently, at Pc greater than 9.53 cmH2O, isogravimetric conditions were never achieved. In 12 additional experiments, the perfusate's colloid osmotic pressure (II) was increased from 12 to 37 mmHg with albumin. On average, Pcrit increased from 12.2 to 23 cmH2O. Using the changes in Pcrit and II, we estimated the microvascular drag reflection coefficient for albumin (sigma d) to be 0.67. After the addition of albumin, Pc less than Pcrit induced constant weight loss along the same Qf-to-Pc relationship. To control for time, five additional lobes were observed at constant Pc for 100-180 min. Slight acceleration of the rate of weight gain occurred after they increased their weight by 30-40%. The low Kf and high sigma d, as well as the stability of the preparation, suggest a well-preserved microvasculature. Qf at Pc between 12 and 24 cmH2O did not influence measurements of Kf using the weight transient method. The low Pcrit may reflect obliteration of lymphatic channels. .A Hancock BJ; Hoppensack M; Oppenheimer L. .I 201220 .U 90008513 .S J Appl Physiol 9001; 67(2):636-42 .M Adaptation, Physiological/*; Animal; Comparative Study; Female; Hindlimb; Isometric Contraction; Muscles/*PH; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't; Time Factors; Weight Gain; Weightlessness. .T Influence of weight bearing on the adaptations of rat plantaris to ablation of its synergists. .P JOURNAL ARTICLE. .W The present study was designed to determine the contribution of weight bearing to the adaptations of the plantaris (PL) to synergist removal. PL from female rats were exposed to 28 days of a simultaneous condition of synergist ablation and hindlimb suspension. At 28 days, contractile responses and morphological measures were obtained and compared with muscles that either had synergists intact or were weight bearing or a combination of both. Synergist ablation prolonged PL maximum isometric twitch tension (Pt), time to peak tension (12%), and one-half relaxation time (12%); increased Pt (26%), maximum isometric tetanic tension (Po, 44%), fatigue resistance (FI, 42%), and fast fiber cross-sectional area (FT CSA, 20%); and decreased Pt/Po (13%) over nonablation counterparts. Suspension decreased PL Pt (26%), Po (26%), rest length (16%), FT CSA (31%), and slow-twitch fiber (ST) number (24%) but increased FI (75%) over weight-bearing counterparts. PL from weight-bearing animals were heavier than from suspended animals, and the extent of this response was greatest after synergist removal. Whole muscle and ST CSA and ST area contribution were greater only in weight-bearing synergist ablation muscles. Daily weight bearing (4 h) in synergist ablation hindlimb suspension groups caused PL weights and ST expressions to be halfway between 24-h suspension and 24-h weight-bearing groups. Our results suggest that weight bearing is not essential to the induction of several adaptations associated with synergist ablation but is required to cause the large muscle mass and ST expression characteristic of this model. .A Michel RN; Olha AE; Gardiner PF. .I 201221 .U 90008515 .S J Appl Physiol 9001; 67(2):648-54 .M Adenosine Diphosphate/AN; Adenosine Monophosphate/AN; Adenosine Triphosphate/AN; Adult; Biopsy; Comparative Study; Fatigue/*; Glucosephosphates/AN; Human; Lactates/AN; Male; Muscle Contraction/*; Muscles/*ME/PA; Phosphocreatine/AN; Support, Non-U.S. Gov't; Time Factors. .T Relationship of contraction capacity to metabolic changes during recovery from a fatiguing contraction. .P JOURNAL ARTICLE. .W The relationship between changes in muscle metabolites and the contraction capacity was investigated in humans. Subjects (n = 13) contracted (knee extension) at a target force of 66% of the maximal voluntary contraction force (MVC) to fatigue, and the recovery in MVC and endurance (time to fatigue) were measured. Force recovered rapidly [half-time (t 1/2) less than 15 s] and after 2 min of recovery was not significantly different (P greater than 0.05) from the precontraction value. Endurance recovered more slowly (t 1/2 approximately 1.2 min) and was still significantly depressed after 2 and 4 min of recovery (P less than 0.05). In separate experiments (n = 10) muscle biopsy specimens were taken from the quadriceps femoris muscle before and after two successive contractions to fatigue at 66% of MVC with a recovery period of 2 or 4 min in between. The muscle content of high-energy phosphates and lactate was similar at fatigue after both contractions, whereas glucose 6-phosphate was lower after the second contraction (P less than 0.05). During recovery, muscle lactate decreased and was 74 and 43% of the value at fatigue after an elapsed period of 2 and 4 min, respectively. The decline in H+ due to lactate disappearance is balanced, however, by a release of H+ due to resynthesis of phosphocreatine, and after 2 min of recovery calculated muscle pH was found to remain at a low level similar to that at fatigue.(ABSTRACT TRUNCATED AT 250 WORDS) .A Sahlin K; Ren JM. .I 201222 .U 90008516 .S J Appl Physiol 9001; 67(2):655-62 .M Animal; Comparative Study; Diaphragm/*PH; Dogs; Fluoroscopy; Lung Volume Measurements; Posture; Respiration; Respiratory Muscles/*PH/RA; Support, U.S. Gov't, P.H.S.; Thoracic Radiography; Tidal Volume; Time Factors. .T In vivo regional diaphragm function in dogs. .P JOURNAL ARTICLE. .W A biplane videofluorographic system was used to track the position of metallic markers affixed to the abdominal surface of the left hemidiaphragm in supine anesthetized dogs. Regional shortening was determined from intermarker distances of rows of markers placed along muscle bundles in the ventral, middle, and dorsal regions of the costal diaphragm and of one row on the crural diaphragm. Considerable variability of regional shortening was seen in a given row, which was reproducible on repeat study in individual dogs but which differed between mechanical ventilation and spontaneous breathing. There were no consistent patterns among dogs. Regional shortening obtained from the change in length of rows extending from chest wall to central tendon showed no consistent differences among dogs during spontaneous breathing. At equal tidal volumes, all regions (except the ventral costal diaphragm) shortened more during spontaneous breathing than during mechanical ventilation. .A Sprung J; Deschamps C; Hubmayr RD; Walters BJ; Rodarte JR. .I 201223 .U 90008517 .S J Appl Physiol 9001; 67(2):663-70 .M Animal; Comparative Study; Dogs; Lung/*BS/PH; Lung Volume Measurements; Perfusion; Pulmonary Embolism/*CO; Serum Albumin/DU; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Tritium/ME; Water/*ME. .T Influence of size of emboli on extravascular lung water. .P JOURNAL ARTICLE. .W We examined the influence of the size of emboli on the vascular volume (QL) and extravascular volume (Qev) accessible to 3HOH during a single pass through an isolated dog lung lobe using the double indicator-dilution method with 125I-human serum albumin as the vascular indicator. As successively more beads of a given diameter (58, 548, or 3,175 microns) were introduced into a lung lobe, a linear relationship between QL and Qev was obtained as they both decreased. The slope of the graph of QL vs. Qev with progressive embolism was directly proportional to the bead diameter. This suggested an approach for estimating the total vascular volume in vessels smaller than the diameter of the beads before embolization, referred to as Qm. If it is assumed that most of the transvascular diffusional exchange of 3HOH occurs in vessels smaller than the smallest beads (mainly capillaries) and that vessel obstruction does not change the ratio of Qev to the perfused capillary volume, the slope of the plot of QL vs. Qev is an estimate of the fraction, Qm/QL, of the total vascular volume in vessels smaller than the bead diameter. In the dog lung lobes studied, Qm/QL was approximately 0.64 for 58-microns vessels, 0.75 for 548-microns vessels, and 0.82 for 3,175-microns vessels. The results suggest that, with occlusion of vessels greater than or equal to 58 microns, 3HOH does not diffuse significantly into unperfused regions.(ABSTRACT TRUNCATED AT 250 WORDS) .A Dawson CA; Rickaby DA; Linehan JH. .I 201224 .U 90008518 .S J Appl Physiol 9001; 67(2):671-6 .M Aminophylline/*PD; Animal; Calcium/*ME; Comparative Study; Dose-Response Relationship, Drug; Isometric Contraction; Muscle Contraction/*DE; Muscles/*ME; Rana pipiens; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Time Factors. .T Aminophylline enhances contractility of frog skeletal muscle: an effect dependent on extracellular calcium. .P JOURNAL ARTICLE. .W The effects of aminophylline (10-500 microM) on isometric twitch and tetanic forces were studied in vitro on frog semitendinosus muscle. Two hypotheses were tested: 1) that micromolar concentrations of aminophylline enhanced contractility of isolated skeletal muscle and 2) that the potentiating effect of aminophylline was dependent on the presence of extracellular calcium ions. Muscles were removed, placed in aerated Ringer solution at 20 degrees C, attached to a force transducer, and stimulated directly. Muscles in normal Ringer and aminophylline Ringer were compared throughout the frequency-force relationship from twitches to maximum tetanic force. Aminophylline increased twitch force significantly at concentrations as low as 25 microM. Over a range of stimulation frequencies, but especially at 10 and 20 Hz, aminophylline increased tetanic force. The potentiating effect of aminophylline (100 microM) was reduced or eliminated in calcium-free Ringer containing 10 mM magnesium. We conclude that aminophylline, at therapeutic concentrations, enhances muscle contractility, and the enhancement is dependent on the presence of extracellular calcium. These findings support the concept that aminophylline is effective in improving respiration in humans with airway obstruction by enhancing diaphragmatic contractility. .A Ridings JW; Barry SR; Faulkner JA. .I 201225 .U 90008519 .S J Appl Physiol 9001; 67(2):677-81 .M Adult; Comparative Study; Exercise Test; Exertion/*; Female; Human; Lactates/BL; Male; Muscles/*PH; Oxygen Consumption/*; Time Factors. .T Recovery of short-term power after dynamic exercise. .P JOURNAL ARTICLE. .W The intensity of prior cycle ergometer exercise alters the pattern in recovery of maximal short-term power output (STPO). STPO was measured on an isokinetic dynamometer after 0, 1, 2, 3, 4, and 8 min of recovery. Immediately after exercise, STPO fell to 85, 75, 55, and 47% of preexercise values for prior exercise equivalent to 60, 80, 100, and 120% of maximal O2 uptake, respectively. STPO had fully recovered by 1 min of postexercise after submaximal work rates (60 and 80%). Recovery was delayed until after 4 min of postexercise after maximal exercise (100%). STPO remained at approximately 90% of preexercise values 8 min postexercise after supramaximal exercise (120%). STPO immediately after exercise and during recovery was inversely proportional to prior exercise intensity. The recovery curve for STPO was similar to that previously reported for creatine phosphate resynthesis after dynamic and isometric exercise. The absolute STPO regained in the initial phase was not inversely proportional to either exercise intensity or 4-min postexercise blood lactate levels, which suggests that factors other than changes in pH alone may mediate initial power recovery. .A Hitchcock HC. .I 201226 .U 90008520 .S J Appl Physiol 9001; 67(2):682-7 .M Afferent Pathways; Animal; Comparative Study; Dogs; Epithelium/CY; Lung/*ME; Lung Compliance; Mucous Membrane/SE; Reflex/*PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Time Factors; Trachea/IR/*SE; Vagus Nerve/*PH. .T Pulmonary rapidly adapting receptors reflexly increase airway secretion in dogs. .P JOURNAL ARTICLE. .W We attempted to determine whether stimulation of pulmonary rapidly adapting receptors (RARs) increase tracheal submucosal gland secretion in anesthetized open-chest dogs. Electroneurographic studies of pulmonary afferents established that RARs but not lung C-fibers were stimulated by intermittent lung collapse during deflation, collapse being produced by removing positive end-expiratory pressure (PEEP, 4 cmH2O) or by applying negative end-expiratory pressure (NEEP, -4 cmH2O). We measured tracheal secretion by the "hillocks" method. Removing PEEP or applying NEEP for 1 min increased secretion from a base line of 6.0 +/- 1.1 to 11.8 +/- 1.7 and 22.0 +/- 2.8 hillocks.cm-2.min-1, respectively (P less than 0.005). After PEEP was restored, dynamic lung compliance (Cdyn) was 37% below control, and secretion remained elevated (P less than 0.05). A decrease in Cdyn stimulates RARs but not other pulmonary afferents. Hyperinflation, which restored Cdyn and RAR activity to control, returned secretion rate to base line. Secretory responses to lung collapse were abolished by vagal cooling (6 degrees C), by pulmonary vagal section, or by atropine. We conclude that RAR stimulation reflexly increases airway secretion. We cannot exclude the possibility that reduced input from slowly adapting stretch receptors contributed to the secretory response. .A Yu J; Schultz HD; Goodman J; Coleridge JC; Coleridge HM; Davis B. .I 201227 .U 90008521 .S J Appl Physiol 9001; 67(2):688-93 .M Animal; Comparative Study; Epithelium/CY; Oxygen/*ME; Permeability; Pulmonary Alveoli/*ME; Pulmonary Surfactants/*PH; Rabbits; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Time Factors; Vitamin B 12/ME. .T Surfactant replacement attenuates the increase in alveolar permeability in hyperoxia. .P JOURNAL ARTICLE. .W Rabbits exposed to hyperoxia develop surfactant deficiency, abnormal lung mechanics, and increased permeability to solute. We investigated whether replenishment of depleted alveolar surfactant by the intratracheal instillation of calf lung surfactant extract (CLSE) would mitigate the increase in alveolar permeability to solute. Twenty-eight rabbits were exposed to 100% O2 for 72 h and received intratracheal instillations of 125 mg CLSE (approximately 170 mumol dipalmitoyl phosphatidylcholine) at 24 and 48 h. The interlobar and intralobar distribution of CLSE was quantified by adding [14C]dipalmitoyl phosphatidylcholine liposes into the instillate and measuring the levels of activity in lung tissue. CLSE was nonuniformly distributed in the different lung lobes, the right lower lobe receiving more CLSE than the rest. Alveolar epithelial permeability to solute was assessed by instilling 10 ml isotonic saline, which contained a trace amount of [57Co]cyanocobalamin, in the right lower lobe and measuring the disappearance of the tracer from the alveolar saline and its appearance in the arterial blood during a 1-h period. CLSE treatment was associated with significantly increased 72-h survival in hyperoxia compared with saline-treated controls (number of survivors: 16/17 vs. 5/11, P less than 0.01). CLSE treatment significantly reduced the rate constant for the movement of cyanocobalamin out of the alveolar space (24 +/- 5 vs. 42 +/- 6 min-1 x 10(-3), P less than 0.01) and tracer appearance in the blood at the end of the study (7 +/- 1 vs. 34 +/- 13%, P less than 0.01) when compared with values in saline controls.(ABSTRACT TRUNCATED AT 250 WORDS) .A Engstrom PC; Holm BA; Matalon S. .I 201228 .U 90008522 .S J Appl Physiol 9001; 67(2):694-8 .M Adult; Comparative Study; Diaphragm/*PH; Fluoroscopy; Human; Inspiratory Reserve Volume; Lung Volume Measurements; Male; Maximal Voluntary Ventilation; Plethysmography/*; Respiratory Muscles/*PH/RA; Thorax/ME; Total Lung Capacity. .T Diaphragmatic displacement measured by fluoroscopy and derived by Respitrace. .P JOURNAL ARTICLE. .W In eight healthy volunteers we simultaneously measured the axial diaphragmatic motion by fluoroscopy and the cross-sectional area changes of the rib cage (RC) and abdomen (ABD) by Respitrace (RIP) during semistatic vital capacities (VC). We found that, if the fluoroscopic axial displacement of the posterior part of the diaphragm between residual volume (RV) and total lung capacity (TLC) is considered equal to 100%, the movement of the middle part is 90%, whereas that of the anterior part is only approximately 60%; the ratio of the axial displacements to mouth volume, furthermore, decreases at high lung volumes, especially for the anterior part. The RIP signal is nearly linearly related to mouth volume, but the contribution of the RC (delta RC) progressively increases (and is approximately 80% RIP at TLC), whereas the volume contribution of the ABD (delta ABD) levels off (to 20% RIP at TLC). The diaphragmatic volume displacement calculated from the theoretical analysis described by Mead and Loring also levels off at high volumes similarly as the ABD but is approximately 50% RIP at TLC. Finally, the axial movements of the three parts of the diaphragm are linearly related to the RC and ABD cross-sectional-area changes (r 0.91-0.97) and are even significantly better correlated with the "calculated" diaphragmatic volume displacement. .A Verschakelen JA; Deschepper K; Jiang TX; Demedts M. .I 201229 .U 90008524 .S J Appl Physiol 9001; 67(2):707-12 .M Animal; Comparative Study; Dogs/*PH; Mathematics; Residual Volume; Respiratory System/*PH; Ribs/*AH; Support, U.S. Gov't, P.H.S.; Thorax/AH; Tomography, X-Ray Computed; Total Lung Capacity. .T Geometry and kinematics of dog ribs. .P JOURNAL ARTICLE. .W Five anesthetized supine beagle dogs were scanned using a fast, multislice computed tomographic X-ray technique to determine the orientation of the ribs at total lung capacity (TLC) and functional residual capacity (FRC). A plane was fit to each rib using a coordinate system in which the z-axis was aligned approximately cephalocaudally and the x-z-plane coincided with the sagittal midplane. The orientation of each plane was described by "pump-handle" and "bucket-handle" angles. The ribs rotated downward and inward during a passive deflation of the lungs from TLC to FRC. Rib displacement was not uniform: bucket-handle motion was predominant in the upper ribs, and pump- and bucket-handle motions were equal in the lower ribs. The change in the pump-handle angles between TLC and FRC was approximately 6 degrees for ribs 3-8, and the change in the bucket-handle angles decreased with rib number from 16 degrees for rib 3 to 6 degrees for rib 8. Rib shape was described by fitting an ellipse to the data for each rib; the ribs became larger and more circular with increasing rib number. .A Margulies SS; Rodarte JR; Hoffman EA. .I 201230 .U 90008525 .S J Appl Physiol 9001; 67(2):713-9 .M Acetylcholine/ME; Animal; Calcium/*ME; Comparative Study; Epithelium/CY; Isometric Contraction; Muscle, Smooth/*PH; Potassium Chloride/ME; Rabbits; Temperature/*; Trachea/ME/*PH. .T Epithelial modulation of trachealis muscle tension is calcium and temperature dependent. .P JOURNAL ARTICLE. .W The tracheobronchial epithelium produces inhibitory substance(s) that alter the tracheal smooth muscle tension. This study examined the effect of changes in extracellular Ca2+ and temperature in vitro on the tension response of rabbit trachealis muscle to mechanical removal of the epithelium. Tension during acetylcholine- and KCl-induced contractions was examined at 0, 0.75, 1.5, 2.5, and 5 mM bath Ca2+ concentrations and at 37, 30, 23, and 41 degrees C bath temperature. At most extracellular Ca2+ concentrations (i.e., 0.75, 1.5, 2.5, and 5 mM), epithelial removal shifted the acetylcholine concentration response approximately one-half log to the left (P less than 0.001 for each condition) but had no effect on the responses to KCl (P = NS). Reductions in bath Ca2+ to 0 mM eliminated the epithelial inhibitory effect on the acetylcholine response. In contrast to the effects of reductions in Ca2+, cooling the airway to 30 and 23 degrees C progressively diminished the magnitude of the epithelial inhibitory effect. Our results indicate that the influence of the tracheal epithelium on tracheal smooth muscle responses to constrictor agonists is substance specific and can be diminished by reductions in tracheal temperature and extracellular Ca2+ concentration. .A Lev A; Christensen GC; Ryan JP; Wang M; Kelsen SG. .I 201231 .U 90008526 .S J Appl Physiol 9001; 67(2):720-9 .M Animal; Blood Pressure; Comparative Study; Diaphragm/PH; Dogs; Electromyography; Fatigue/*; Heart Rate; Ischemia/*PP; Isometric Contraction; Partial Pressure; Respiration; Respiratory Muscles/BS/*ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Alterations in respiratory muscle activation in the ischemic fatigued canine diaphragm. .P JOURNAL ARTICLE. .W The purpose of the present study was to examine the respiratory motor response to diaphragm fatigue. Studies were performed using in situ diaphragm muscle strips dissected from the left costal diaphragm in anesthetized dogs. The left inferior phrenic artery was isolated, and diaphragmatic strip fatigue was elicited by occluding this vessel. Strip tension, strip electromyographic activity, parasternal electromyographic activity, and the electromyogram of the right hemidiaphragm were recorded during spontaneous breathing efforts before, during, and after periods of phrenic arterial occlusion. In separate trials, we examined the neuromuscular responses to phrenic arterial occlusion at arterial PCO2 (PaCO2) of 40, 55, and 75 Torr. No fatigue and no alteration in electromyographic activities were observed in trials at PaCO2 of 40 Torr. During trials at PaCO2 of 55 and 75 Torr, however, diaphragm tension fell, the peak height of the diaphragm strip electromyogram decreased, and the peak heights of the parasternal and right hemidiaphragm electromyograms increased. Relief of phrenic arterial occlusion resulted in a return of strip tension and all electromyograms toward base-line values. In additional experiments, the left phrenic nerve was sectioned in the chest after producing fatigue. Phrenic section was followed by an increase in the peak height of the left phrenic neurogram (recorded above the site of section). This latter finding suggests that diaphragm strip motor drive may be reflexly inhibited during the development of fatigue by neural traffic carried along phrenic afferents. .A Supinski GS; DiMarco AF; Hussein F; Altose MD. .I 201232 .U 90008527 .S J Appl Physiol 9001; 67(2):730-5 .M Animal; Comparative Study; Dogs; Female; Hemodynamics; Male; Oxygen Consumption/*; Partial Pressure; Pulmonary Alveoli/*PH; Pulmonary Circulation; Pulmonary Gas Exchange/*; Respiration; Support, U.S. Gov't, P.H.S.; Ventilation-Perfusion Ratio. .T Effect of regional alveolar hypoxia on gas exchange in dogs. .P JOURNAL ARTICLE. .W We studied the effects of left lower lobe (LLL) alveolar hypoxia on pulmonary gas exchange in anesthetized dogs using the multiple inert gas elimination technique (MIGET). The left upper lobe was removed, and a bronchial divider was placed. The right lung (RL) was continuously ventilated with 100% O2, and the LLL was ventilated with either 100% O2 (hyperoxia) or a hypoxic gas mixture (hypoxia). Whole lung and individual LLL and RL ventilation-perfusion (VA/Q) distributions were determined. LLL hypoxia reduced LLL blood flow and increased the perfusion-related indexes of VA/Q heterogeneity, such as the log standard deviation of the perfusion distribution (log SDQ), the retention component of the arterial-alveolar difference area [R(a-A)D], and the retention dispersion index (DISPR*) of the LLL. LLL hypoxia increased blood flow to the RL and reduced the VA/Q heterogeneity of the RL, indicated by significant reductions in log SDQ, R(a-A)D, and DISPR*. In contrast, LLL hypoxia had little effect on gas exchange of the lung when evaluated as a whole. We conclude that flow diversion induced by regional alveolar hypoxia preserves matching of ventilation to perfusion in the whole lung by increasing gas exchange heterogeneity of the hypoxic region and reducing heterogeneity in the normoxic lung. .A Domino KB; Hlastala MP; Eisenstein BL; Cheney FW. .I 201233 .U 90008530 .S J Appl Physiol 9001; 67(2):749-55 .M Airway Obstruction/*CO; Comparative Study; Human; Infant; Infant, Newborn; Muscles/PH; Reflex; Respiration; Respiratory Airflow; Respiratory System/*PP; Sleep/*; Support, U.S. Gov't, P.H.S.; Tidal Volume; Tracheostomy. .T Influence of upper airway negative pressure reflex on response to airway occlusion in sleeping infants. .P JOURNAL ARTICLE. .W Artificially produced upper airway suction inhibits the diaphragm in animals and infants; however, the effects of spontaneously generated suction in humans are unknown. We studied nine tracheostomized infants because separation of the upper from the lower airway allowed us to channel suction created by an occluded inspiratory effort to both upper and lower airways (upper + lower airway occlusions) or to the lower airway only (lower airway occlusion). The tracheostomy airway was briefly occluded at end expiration during quiet sleep. In upper + lower airway occlusions, peak airway pressure of the first occluded breath was less negative and rate of pressure decrease slower than that of lower airway occlusions, indicating that upper airway suction inhibits thoracic inspiratory muscles. The threshold for this response was less than or equal to 4 cmH2O suction pressure. The effect on inspiratory time was variable. A decrease in slope of the inspiratory pressure waveform occurring at approximately 0.12 s after inspiration onset was more marked in upper + lower airway occlusions. We conclude that infants have an upper airway reflex response to inspiratory pressure that alters not only the peak and slope but also the shape of the inspiratory pressure waveform. .A Thach BT; Schefft GL; Pickens DL; Menon AP. .I 201234 .U 90008532 .S J Appl Physiol 9001; 67(2):765-70 .M Anemia/*PP; Animal; Blood Glucose/AN; Comparative Study; Exercise Test; Exertion/*; Female; Hematocrit; Hemoglobins/AN; Lactates/BL; Muscles/*EN; Oxidoreductases/*AN; Oxygen Consumption; Physical Conditioning, Animal; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't. .T Interactive effects of anemia and muscle oxidative capacity on exercise endurance. .P JOURNAL ARTICLE. .W We used endurance training and acute anemia to assess the interactions among maximal oxygen consumption (VO2max), muscle oxidative capacity, and exercise endurance in rats. Animals were evaluated under four conditions: untrained and endurance-trained with each group subdivided into anemic (animals with reduced hemoglobin concentrations) and control (animals with unchanged hemoglobin concentrations). Anemia was induced by isovolemic plasma exchange transfusion. Hemoglobin concentration and hematocrit were decreased by 38 and 41%, respectively. Whole body VO2max was decreased by 18% by anemia regardless of training condition. Anemia significantly reduced endurance by 78% in untrained rats but only 39% in trained animals. Endurance training resulted in a 10% increase in VO2max, a 75% increase in the distance run to exhaustion, and 35, 45, and 58% increases in skeletal muscle pyruvate-malate, alpha-ketoglutarate, and palmitylcarnitine oxidase activities, respectively. We conclude that endurance is related to the interactive effects of whole body VO2max and muscle oxidative capacities for the following reasons: 1) anemic untrained and trained animals had similar VO2max but trained rats had higher muscle oxidative capacities and greater endurance; 2) regardless of training status, the effect of acute anemia was to decrease VO2max and endurance; and 3) trained anemic rats had lower VO2max but had greater muscle oxidative capacity and greater endurance than untrained controls. .A Gregg SG; Willis WT; Brooks GA. .I 201235 .U 90008533 .S J Appl Physiol 9001; 67(2):771-9 .M Intubation, Intratracheal/*; Lung Volume Measurements; Mathematics; Maximal Expiratory Flow Rate; Models, Theoretical; Respiratory System/ME; Trachea/*PH. .T Effect of air entrainment on airway pressure during endotracheal gas injection. .P JOURNAL ARTICLE. .W Turbulent jets in endotracheal tubes induce air entrainment and airway pressure changes. We attempted to understand the physical explanation for these effects, which open up to a wide range of applications in intubated patients. An in vitro study was performed on standard size endotracheal tubes with diameters of 8, 7, and 3 mm and several capillaries molded into the wall (less than 1 mm diam) allowing gas injection at approximately 1-2 cm from the tracheal end of the endotracheal tube. This produced a jet velocity-dependent gain in tracheal pressure (Ptr) during inspiration. Data have been interpreted with a theory, based on the classic momentum theorem, which indicates that the mechanisms involved resemble those of axisymmetrical confined jets: air entrainment by turbulent friction with a longitudinal increase in lateral pressure. The difference with axisymmetrical systems lies in the nonconservation of the total thrust in our system because, secondary to wall friction and to the nonaxial incidence of the jets, only a fraction of the jet momentum flux is transformed into pressure. This suggests faster mixing in the present lateral jet system, as shown by 1) the independence of Ptr on tracheal geometry and 2) the very rapid increase in lateral pressure. The present study supports the idea that pressure changes in the airways, which are potentially beneficial in intubated patients, can be satisfactorily generated by turbulent jets. .A Isabey D; Boussignac G; Harf A. .I 201236 .U 90008534 .S J Appl Physiol 9001; 67(2):780-5 .M Adult; Asthma/CO; Comparative Study; Female; Forced Expiratory Flow Rates/*; Forced Expiratory Volume; Human; Lung Volume Measurements; Male; Maximal Expiratory Flow-Volume Curves/*; Maximal Midexpiratory Flow Rate; Plethysmography; Pulmonary Gas Exchange; Respiration/*; Respiratory Airflow; Spirometry; Support, U.S. Gov't, P.H.S.; Thorax/*PH. .T Effects of thoracic gas compression on maximal and partial flow-volume maneuvers. .P JOURNAL ARTICLE. .W Airway hysteresis can be evaluated by comparing maximal (MEFV) and partial (PEFV) expiratory flow-volume curves. The maneuvers are often obtained from pulmonary function systems that are subject to gas-compression artifacts. Because gas-compression artifacts might differentially affect PEFV vs. MEFV curves, we simultaneously obtained MEFV and PEFV curves by use of a spirometer and a volume-displacement plethysmograph (a method not subject to gas-compression artifacts) in normal and asthmatic subjects. Plethysmographic flow rates exceeded spirometric flow rates on all MEFV and PEFV maneuvers. When maximal flow exceeded partial flow (or vice versa) in the plethysmograph, the same result was virtually always observed for spirometric measurements. Alveolar pressure (PA) was higher on MEFV than on PEFV maneuvers in asthmatic subjects; comparisons between PA (on PEFV and MEFV maneuvers) in normal subjects varied at different lung volumes. Ratios of Vmax on PEFV maneuvers to Vmax on MEFV maneuvers (Vmax-p/Vmax-c) obtained from a volume-displacement plethysmograph differ quantitatively from ratios determined in systems subject to gas-compression artifacts; qualitatively, however, failure to account for thoracic gas compression ordinarily will not influence the ability to identify airway hysteresis (or lack thereof) by use of Vmax-p-to-Vmax-c ratios. .A Fairshter RD; Berry RB; Wilson AF; Brideshead T; Mukai D. .I 201237 .U 90008535 .S J Appl Physiol 9001; 67(2):786-91 .M Adult; Angiotensin I/AI/BL/*PH; Angiotensin II/BL; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Cardiac Output; Comparative Study; Enalapril/*PD; Epinephrine/BL; Female; Gravitation; Heart Rate; Hemodynamics/*DE; Human; Male; Norepinephrine/BL; Splanchnic Circulation/*DE; Support, Non-U.S. Gov't. .T Effects of angiotensin blockade on the splanchnic circulation in normotensive humans. .P JOURNAL ARTICLE. .W The effects of angiotensin-converting enzyme inhibition (ACE-I) by enalapril on splanchnic (n = 10) and central hemodynamics (n = 9) were examined in moderately salt-depleted healthy volunteers, at rest and during 15-20 min of lower body negative pressure (LBNP), reducing mean arterial pressure by 10 mmHg. During LBNP before ACE-I, both splanchnic and total peripheral vascular resistances increased. During ACE-I, splanchnic and total peripheral vascular resistances decreased. After enalapril administration, splanchnic vascular resistance did not increase during LBNP. Total peripheral vascular resistance still increased but not to the same extent as during LBNP before ACE-I. The increases in heart rate and plasma norepinephrine during LBNP were attenuated after ACE-I compared with LBNP before ACE-I. The effectiveness of the ACE-I was clearly demonstrated by unchanged and low plasma angiotensin II levels during ACE-I. We conclude that, in normal sodium-depleted humans, acute ACE-I decreases splanchnic vascular resistance at rest and abolishes splanchnic vasoconstriction during LBNP. Furthermore, it may interfere with autonomic nervous system control of the circulation. .A Stadeager C; Hesse B; Henriksen O; Christensen NJ; Bonde-Petersen F; Mehlsen J; Giese J. .I 201238 .U 90008536 .S J Appl Physiol 9001; 67(2):792-6 .M Adenosine Monophosphate/*PD; Administration, Inhalation; Adult; Airway Resistance/*DE; Asthma/*DT; Breath Tests; Comparative Study; Female; Forced Expiratory Volume; Human; Male; Methacholine Compounds/*PD; Middle Age; Support, Non-U.S. Gov't; Time Factors. .T Inhalation of adenosine 5'-monophosphate increases methacholine airway responsiveness. .P JOURNAL ARTICLE. .W Airway hyperresponsiveness is a characteristic feature in asthmatic subjects, but the mechanism of the hyperresponsiveness is not known. The purpose of this study was to investigate whether methacholine airway responsiveness was increased 24 h after inhalation of adenosine 5'-monophosphate (AMP). Ten atopic asthmatic subjects and six atopic normal subjects were studied on 4 study days. On the 1st day, a methacholine inhalation test was performed, followed within 48 h by an AMP inhalation test. Seven days later the second AMP test was performed, and 24 h later the methacholine inhalation test was repeated. Response was measured using partial flow-volume curves, and the concentration required to cause a 40% fall in the partial flow-volume curve (PC40) was calculated. The geometric mean methacholine PC40 fell from 1.36 mg/ml on day 1 (before AMP inhalation) to 0.71 mg/ml on day 4 (24 h after AMP inhalation, P less than 0.01). There was no change in the mean PC40 for adenosine on the 2 study days (5.82 and 7.06 mg/ml, P greater than 0.1). These findings suggest that adenosine release may contribute to the increase in airway responsiveness after allergen challenge. .A Rosati G; Hargreave FE; Ramsdale EH. .I 201239 .U 90008537 .S J Appl Physiol 9001; 67(2):797-803 .M Animal; Carotid Body/*PH; Carotid Sinus/IR; Cats; Comparative Study; Female; Oxygen Consumption/*; Pregnancy; Pregnancy, Animal/*; Pressoreceptors; Respiration/*; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Tidal Volume. .T Influence of pregnancy on ventilatory and carotid body neural output responsiveness to hypoxia in cats. .P JOURNAL ARTICLE. .W Pregnancy increases ventilation and ventilatory sensitivity to hypoxia and hypercapnia. To determine the role of the carotid body in the increased hypoxic ventilatory response, we measured ventilation and carotid body neural output (CBNO) during progressive isocapnic hypoxia in 15 anesthetized near-term pregnant cats and 15 nonpregnant females. The pregnant compared with nonpregnant cats had greater room-air ventilation [1.48 +/- 0.24 vs. 0.45 +/- 0.05 (SE) l/min BTPS, P less than 0.01], O2 consumption (29 +/- 2 vs. 19 +/- 1 ml/min STPD, P less than 0.01), and lower end-tidal PCO2 (30 +/- 1 vs. 35 +/- 1 Torr, P less than 0.01). Lower end-tidal CO2 tensions were also observed in seven awake pregnant compared with seven awake nonpregnant cats (28 +/- 1 vs. 31 +/- 1 Torr, P less than 0.05). The ventilatory response to hypoxia as measured by the shape of parameter A was twofold greater (38 +/- 5 vs. 17 +/- 3, P less than 0.01) in the anesthetized pregnant compared with nonpregnant cats, and the CBNO response to hypoxia was also increased twofold (58 +/- 11 vs. 29 +/- 5, P less than 0.05). The increased CBNO response to hypoxia in the pregnant compared with the nonpregnant cats persisted after cutting the carotid sinus nerve while recording from the distal end, indicating that the increased hypoxic sensitivity was not due to descending central neural influences. We concluded that greater carotid body sensitivity to hypoxia contributed to the increased hypoxic ventilatory responsiveness observed in pregnant cats. .A Hannhart B; Pickett CK; Weil JV; Moore LG. .I 201240 .U 90008539 .S J Appl Physiol 9001; 67(2):811-6 .M Animal; Blood Gas Analysis; Bronchoalveolar Lavage Fluid/AN; Comparative Study; Fatty Acids, Essential/*DF; Irrigation; Leukocyte Count; Leukotrienes B/AN; Lung/*IN/ME/RI; Oleic Acids/*PD; Permeability; Platelet Count; Radioimmunoassay; Rats; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; SRS-A/AN; Time Factors. .T Essential fatty acid-deficient rats are resistant to oleic acid-induced pulmonary injury. .P JOURNAL ARTICLE. .W Because leukotrienes and prostaglandins are inflammatory mediators derived from arachidonic acid, their potential role in oleic acid-induced lung injury was evaluated in control and in essential fatty acid-deficient (EFAD) rats depleted of arachidonic acid substrate. In control rats, oleic acid (0.06 ml/kg iv) increased the pulmonary permeability index (measured by scintigraphy) from -10 +/- 13 x 10(-6) s-1 to 217 +/- 20 x 10(-6) s-1 and 118 +/- 13 x 10(-6) s-1 at 5 and 50 min (P less than 0.05), respectively. It also caused arterial hypoxemia at 30 min (P less than 0.05). Compared with saline controls, oleic acid increased bronchoalveolar lavage fluid levels of immunoreactive (i) LTC4/D4, iLTB4, (P less than 0.01), and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) (P less than 0.05). In EFAD rats, oleic acid failed to significantly increase the lung permeability index at 5 and 50 min. In contrast to control rats, oleic acid failed to cause hypoxemia in the EFAD rats. Bronchoalveolar lavage levels of iLTB4 and i6-keto-PGF1 alpha after oleic acid in EFAD rats were lower compared with oleic acid controls, whereas iLTC4/D4 in the oleic acid EFAD group was not decreased. Treatment with intraperitoneal ethyl arachidonate (400 mg over 2 wk) reversed the resistance of EFAD rats such that the pulmonary edema (P less than 0.05) was evident after oleic acid. This latter group also manifested a significant (P less than 0.05) rise in the bronchoalveolar lavage levels of iLTB4 and i6-keto-PGF1 alpha. These results suggest that arachidonic acid metabolites contribute to oleic acid-induced pulmonary permeability. .A Ball HA; Cook JA; Spicer KM; Wise WC; Halushka PV. .I 201241 .U 90008541 .S J Appl Physiol 9001; 67(2):824-32 .M Animal; Animals, Newborn/*PH; Biological Transport; Chlorides/ME; Comparative Study; Epithelium/CY; Macromolecular Systems; Membrane Potentials; Mucociliary Clearance/*; Sheep; Sodium/ME; Support, U.S. Gov't, P.H.S.; Time Factors; Trachea/*GD/SE; Water/ME. .T Developmental changes in the tracheal mucociliary system in neonatal sheep. .P JOURNAL ARTICLE. .W We studied the postnatal development of the tracheal epithelium and mucociliary system in neonatal sheep. Secretion of macromolecules (radiolabeled with 35SO4 and [3H]-threonine), unidirectional fluxes of Cl-, Na+, and water (measured with radioactive tracers), and ciliary beat frequency (CBF) were measured in tracheal tissues in vitro. Tracheal mucus transport velocity (TMV) was measured in vivo. Sheep were studied at 0, 2, 4, 8, and greater than 24 (adult) wk after birth. In newborn sheep trachea, secretion of macromolecules was significantly elevated (cf. adults), and there was basal net secretion of Cl- under short-circuit and open-circuit conditions. This induced open-circuit secretion of Na+. Secretion of macromolecules decreased rapidly by 2 wk (by 40-50%) and was not different from adult values by 4 wk. Active Na+ absorption developed rapidly, and from 2 wk onward it predominated under open-circuit conditions, inducing net Cl- absorption. These changes in secretory function were associated with an age-related increase in TMV, whereas inherent tracheal CBF was unchanged. In sheep, therefore, the newborn's trachea has elevated secretion of macromolecules and secretes Cl- and liquid under basal conditions. Normal secretory function (a reduction in secretion of macromolecules coupled with net absorption of ions and presumably of liquid also) approaches adult function by 2-4 wk of age. .A Phipps RJ; Abraham WM; Mariassy AT; Torrealba PJ; Sielczak MW; Ahmed A; McCray M; Stevenson JS; Wanner A. .I 201242 .U 90008542 .S J Appl Physiol 9001; 67(2):833-8 .M Afferent Pathways; Animal; Aorta/*IR; Blood Gas Analysis; Carotid Sinus/*IR; Chemoreceptors/ME; Comparative Study; Dogs; Hemodynamics; Lung/*BS; Lung Diseases/*CI; Oleic Acids/*PD; Oxygen Consumption; Pressoreceptors/ME; Pulmonary Edema/CI; Pulmonary Gas Exchange; Pulmonary Wedge Pressure. .T Sinoaortic deafferentation reduces intrapulmonary shunt in dogs with oleic acid lung injury. .P JOURNAL ARTICLE. .W Hypoxic stimulation of the peripheral chemoreceptors has been reported to inhibit hypoxic pulmonary vasoconstriction. To evaluate the pathophysiological importance of this observation, we investigated the effects of surgical peripheral chemoreceptor denervation on pulmonary vascular tone and gas exchange in 17 pentobarbital-anesthetized dogs with oleic acid pulmonary edema. Pulmonary arterial pressure-cardiac index (Ppa/Q) plots, blood gases, and intrapulmonary shunt measured by the SF6 method were obtained at base line, after peripheral chemodenervation (n = 9) or after sham operation (n = 8), and again after 0.09 ml.kg-1 intravenous oleic acid. Over the range of Q studied (2-5 l.min-1.m-2), Ppa/Q plots were best fitted as first-order polynomials in most dogs in all experimental conditions. Chemoreceptor denervation increased Ppa at the lowest Q, while sham operation did not affect the Ppa/Q plots. Oleic acid increased Ppa over the entire range of Q and increased intrapulmonary shunt. This latter was measured at identical Q during the construction of the Ppa/Q plots. Chemoreceptor-denervated dogs, compared with sham-operated dogs, had the same pulmonary hypertension but lower intrapulmonary shunt (36 +/- 4 vs. 48 +/- 5%, means +/- SE, P less than 0.04) and venous admixture (43 +/- 4 vs. 54 +/- 3%, P less than 0.02). We conclude that in intact dogs chemoreceptor denervation attenuates the rise in intrapulmonary shunt after oleic acid lung injury. Whether this improvement in gas exchange is related to an enhanced hypoxic pulmonary vasoconstriction is uncertain. .A Leeman M; Closset J; Vachiery JL; Lejeune P; Melot C; Naeije R. .I 201243 .U 90008543 .S J Appl Physiol 9001; 67(2):839-45 .M Animal; Bronchoalveolar Lavage Fluid; Comparative Study; Dehydration/*; Dogs; Lung/*PH; Lung Volume Measurements; Pressure; Pulmonary Alveoli/ME; Pulmonary Wedge Pressure/*; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Surface Tension; Time Factors. .T Effect of dehydration on interstitial pressures in the isolated dog lung. .P JOURNAL ARTICLE. .W We have determined the effect of dehydration on regional lung interstitial pressures. We stopped blood flow in the isolated blood-perfused lobe of dog lung at vascular pressure of approximately 4 cmH2O. Then we recorded interstitial pressures by micropuncture at alveolar junctions (Pjct), in perimicrovascular adventitia (Padv), and at the hilum (Phil). After base-line measurements, we ventilated the lobes with dry gas to decrease extravascular lung water content by 14 +/- 5%. In one group (n = 10), at constant inflation pressure of 7 cmH2O, Pjct was 0.2 +/- 0.8 and Padv was -1.5 +/- 0.6 cmH2O. After dehydration the pressures fell to -5.0 +/- 1.0 and -5.3 +/- 1.3 cmH2O, respectively (P less than 0.01), and the junction-to-advential gradient (Pjct-Padv) was abolished. In a second group (n = 6) a combination of dehydration and lung expansion with inflation pressure of 15 cmH2O further decreased Pjct and Padv to -7.3 +/- 0.7 and -7.1 +/- 0.7 cmH2O, respectively. Phil followed changes in Padv. Interstitial compliance was 0.6 at the junctions, 0.8 in adventitia, and 0.9 ml.cmH2O-1.100 g-1 wet lung at the hilum. We conclude, that perialveolar interstitial pressures may provide an important mechanism for prevention of lung dehydration. .A Glucksberg MR; Bhattacharya J. .I 201244 .U 90008545 .S J Appl Physiol 9001; 67(2):856-61 .M Administration, Inhalation; Adolescence; Adult; Asthma/*DT; Bronchi/*DE; Capsaicin/*PD; Comparative Study; Female; Forced Expiratory Volume; Human; Male; N-Isopropylatropine/AD; Reflex/PH; Support, Non-U.S. Gov't; SRS-A/AD; Time Factors; Vagus Nerve/PH. .T Capsaicin-induced bronchodilation in mild asthmatic subjects: possible role of nonadrenergic inhibitory system. .P JOURNAL ARTICLE. .W We investigated whether stimulation of vagal afferent nerve fibers with inhaled capsaicin could induce a nonadrenergic inhibitory reflex in nine mild asthmatic subjects. Changes in total respiratory resistance (Rrs) were measured with a forced oscillation technique. First we induced a rise of 71 +/- 15% in Rrs (P less than 0.001) after leukotriene D4 aerosol. Subsequent inhalation of capsaicin (2 nmol) caused no significant change in mean Rrs of -1.1 +/- 8.2%. After the muscarinic receptor antagonist ipratropium bromide (120 micrograms) was inhaled, leukotriene D4 increased Rrs by 103 +/- 9% (P less than 0.001). Capsaicin subsequently caused bronchodilation in all subjects (Rrs = -22.3 +/- 2.7%, P less than 0.001). Ethanol-saline (diluent) alone caused a nonsignificant fall in Rrs (-9.9 +/- 4.7%) but a deep breath and coughing resulted in bronchodilation (-16.9 +/- 6.1%, P less than 0.05 and -11.6 +/- 2.9%, P less than 0.01, respectively). As observed in normal subjects, capsaicin may initiate an inhibitory reflex, presumably of nonadrenergic origin. This reflex could not be distinguished from that caused by coughing or by deep inhalation. A defect in nonadrenergic mechanisms, at least in mild asthma, seems unlikely. .A Lammers JW; Minette P; McCusker MT; Chung KF; Barnes PJ. .I 201245 .U 90008546 .S J Appl Physiol 9001; 67(2):862-70 .M Adaptation, Physiological; Animal; Cardiac Output; Cardiac Volume; Cattle/*PH; Comparative Study; Exercise Test; Exertion/*; Heart Rate; Hemoglobins/AN; Horses/*PH; Oxygen Consumption/*; Physical Conditioning, Animal; Respiratory System/PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.. .T Oxygen transport during exercise in large mammals. I. Adaptive variation in oxygen demand. .P JOURNAL ARTICLE. .W This study investigated mechanisms used by horses and steers to increase O2 uptake and delivery (VO2) from resting to maximal rates and identified the mechanisms that enable horses to achieve higher maximal rates of O2 consumption (VO2max) than steers. VO2 and circulatory variables were measured while Standardbred trotting horses and steers (450-kg body mass) stood quietly and ran on a treadmill at speeds up to those eliciting VO2max. As VO2 increased in both species, heart rate and circulating hemoglobin (Hb) concentration increased, thereby increasing O2 delivery by the circulation, while cardiac stroke volume remained unchanged. At VO2max arterial PCO2 increased from its resting value in horses but was unchanged in steers, and arterial PO2 decreased in both species. Although the horses hypoventilated and were hypoxemic at VO2max, no significant decrease in arterial Hb saturation occurred. VO2max of the horses was 2.6 times higher than that of the steers and was associated with a 100% larger cardiac output, 100% larger stroke volume, and 40% higher Hb concentration, whereas heart rates at VO2max were identical in the two species. The higher cardiac output of the horses at VO2max resulted from a 1.2-fold higher mean arterial pressure and 1.6-fold lower peripheral tissue resistance (associated with a larger skeletal muscle capillary bed). Both the magnitude of the difference in VO2max between horses and steers and the mechanisms used to achieve it are the same as observed in smaller pairs of mammalian species with large variation in aerobic capacity. .A Jones JH; Longworth KE; Lindholm A; Conley KE; Karas RH; Kayar SR; Taylor CR. .I 201246 .U 90008547 .S J Appl Physiol 9001; 67(2):871-8 .M Animal; Cattle/*PH; Comparative Study; Exercise Test; Exertion/*; Horses/*PH; Lung/UL; Lung Volume Measurements; Oxygen Consumption/*; Pulmonary Alveoli/BS; Pulmonary Circulation; Pulmonary Gas Exchange/*; Respiratory System/PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.. .T Oxygen transport during exercise in large mammals. II. Oxygen uptake by the pulmonary gas exchanger. .P JOURNAL ARTICLE. .W Because the maximal rate of O2 consumption (VO2max) of the horse is 2.6 times larger than that of steers of equal size, we wondered whether their pulmonary gas exchanger is proportionately larger. Three Standardbred racehorses [body mass (Mb) = 447 kg] and three domestic steers (Mb = 474 kg) whose cardiovascular function at VO2max had been thoroughly studied (Jones et al. J. Appl. Physiol. 67: 862-870, 1989) were used to study their lungs by morphometry. The basic morphometric parameters were similar in both species. The nearly 2 times larger lung volumes of the horses caused the gas exchange surfaces and capillary blood volume to be 1.6 to 1.8 times larger. Morphometric pulmonary diffusing capacity was 2 times larger in the horse than in the steer; the 2.6-fold greater rate of O2 uptake thus required the alveolar-capillary PO2 difference to be 1.3 times larger in the horse than in the steer. Combining physiological and morphometric data, we calculated capillary transit time at VO2max to be 0.4-0.5 s. Bohr integration showed capillary blood to be equilibrated with alveolar air after 75 and 58% of transit time in horses and steers, respectively; horses maintain a smaller degree of redundancy in their pulmonary gas exchanger. .A Constantinopol M; Jones JH; Weibel ER; Taylor CR; Lindholm A; Karas RH. .I 201247 .U 90008548 .S J Appl Physiol 9001; 67(2):879-84 .M Animal; Blood Gas Analysis/*VE; Blood Gas Monitoring, Transcutaneous; Body Temperature/*; Cattle/PH; Comparative Study; Exercise Test; Exertion/*; Hemoglobins/AN; Horses/PH; Oxygen Consumption; Physical Conditioning, Animal; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.. .T Blood gas measurements during exercise: errors due to temperature correction. .P JOURNAL ARTICLE. .W This study assessed the degree to which correcting blood gas measurements to rectal temperature (Tre) rather than to the temperatures at which gas exchange occurs [pulmonary arterial (Tpa) or intramuscular (Tm)] introduces errors into blood gas analysis of exercising mammals. Horses and steers weighing 450 kg were run on a treadmill at speeds up to those eliciting maximal rates of O2 consumption (VO2max), and temperatures were measured in various body compartments. In both species Tpa rose faster than Tre during the run, the degree of dissociation being a function of exercise intensity and duration. Tm was measured only in horses, and it rose faster than Tpa during the run and decreased more slowly postrun. Correcting blood gas values measured at an analyzer temperature of 37 degrees C to Tre without accounting for transient increases during the run of Tpa and Tm that were never reflected in Tre significantly biased estimates of blood gases. The biased estimates erroneously indicated that both species experienced more severe hypoxemia than they actually did at VO2max and masked the hypercapnia experienced by the horses at VO2max. .A Jones JH; Taylor CR; Lindholm A; Straub R; Longworth KE; Karas RH. .I 201248 .U 90008549 .S J Appl Physiol 9001; 67(2):885-8 .M Anaerobic Threshold/*; Exercise/*; Human; Lactates/*ME; Models, Biological; Oxygen Consumption. .T Detection of a lactate threshold during incremental exercise? .P JOURNAL ARTICLE. .W An important question in the study of the exercise response is the real or imaginary nature of the anaerobic threshold, and mathematical modeling techniques have been invoked to assist in resolving this issue. Two opposing views with competing data models recently published in this journal are criticized. One view suggests a segmented model with a discontinuous first derivative at the threshold. The other suggests a continuous model over the whole work load range, implying the anaerobic threshold to be imaginary. However, neither group of authors has devoted proper rigorous attention to the models they use. Had this been done, some of the divergence of opinion may have been avoided. Ideal data from an alternate segmented model that has a continuous first derivative at the threshold are considered for comparative purposes. This suggests that the log-log transformation method may well lead to improved detection of a threshold when one exists, although the estimates of the threshold value obtained are unreliable. Modeling methodology is a useful approach to the resolution of scientific issues, but there exist fundamental implications and alternatives that must be fully recognized. .A Morton RH. .I 201249 .U 90008550 .S J Appl Physiol 9001; 67(2):889-93 .M Catheterization, Peripheral; Comparative Study; Esophagus/*ME; Human; Infant, Newborn; Infant, Premature/*; Lung/*PH; Pressure; Pulmonary Wedge Pressure/*; Respiratory Function Tests; Support, Non-U.S. Gov't; Thorax. .T Liquid-filled esophageal catheter for measuring pleural pressure in preterm neonates. .P JOURNAL ARTICLE. .W The precise measurement of esophageal pressure (Pes) as a reflection of pleural pressure (Ppl) is crucial to the measurement of lung mechanics in the newborn. The fidelity of Pes as a measurement of Ppl is determined by the occlusion test in which, during respiratory efforts against an occlusion at the airway opening, changes in pressure (delta Pao) (Pao is assumed to be equal to alveolar pressure) are shown to be equal to changes in Pes (delta Pes). Eight intubated premature infants (640-3,700 g) with chest wall distortion were studied using a water-filled catheter system to measure Pes. During the occlusion test, all patients had a finite region of the esophagus where delta Pes equaled delta Pao, which corresponded to points in the esophagus above the cardia but below the carina. In conclusion, even in the presence of chest wall distortion, a liquid-filled catheter with the tip between the cardia and carina can provide an accurate measurement of Ppl, even in the very small premature infant with chest wall distortion. .A Coates AL; Davis GM; Vallinis P; Outerbridge EW. .I 201250 .U 90008551 .S J Appl Physiol 9001; 67(2):894-901 .M Adult; Blood Flow Velocity; Blood Pressure; Comparative Study; Decompression/*; Exercise/*; Exercise Test; Heart Rate; Human; Leg/AH; Lower Body Negative Pressure/*; Male; Oxygen Consumption; Pressoreceptors/ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Ten weeks of aerobic training do not affect lower body negative pressure responses [published erratum appears in J Appl Physiol 1990 May;68(5):2247] .P JOURNAL ARTICLE. .W Based mostly on cross-sectional data, it has been suggested that aerobic training may decrease lower body negative pressure (LBNP) tolerance through a hypothesized attenuation in both high- and low-pressure baroreflex gain. An experimental group (EXP) of eight male subjects [22.1 +/- 1.4 (SD) yr] underwent a 10-wk treadmill and cycle ergometer training program, which resulted in a 21% increase in maximal O2 uptake (VO2 max), 45.7 +/- 1.5 vs. 55.2 +/- 1.7 (SE) ml.kg-1.min-1; P less than 0.05]. A control group, (CON; n = 7; 27.3 +/- 5.7 yr), which did not undergo training, had no significant changes in VO2 max (49.4 +/- 3.3 vs. 48.8 +/- 3.2 ml.kg-1.min-1). Before and after training the EXP and CON groups participated in LBNP tolerance tests (terminated at presyncope) and neck pressure-suction testing (to describe the carotid sinus-heart rate baroreflex). LBNP tolerance, as defined by three different indexes, and carotid sinus-heart rate baroreflex gain were not altered in either group after training. Furthermore, there were no changes in LBNP heart rate, blood pressure, leg circumference, forearm blood flow, or forearm vascular resistance responses at any level of LBNP challenge after training. In conclusion, 10 wk of aerobic training did not change LBNP tolerance or alter the reflex cardiovascular compensatory mechanisms activated during LBNP. .A Lightfoot JT; Claytor RP; Torok DJ; Journell TW; Fortney SM. .I 201251 .U 90008552 .S J Appl Physiol 9001; 67(2):902 .M Mathematics; Oxygen/*PH; Partial Pressure. .T Determination of PO2 from saturation [letter] .P LETTER. .A Ellis RK. .I 201252 .U 90008553 .S J Appl Physiol 9001; 67(3):1001-6 .M Acrolein/*TO; Aldehydes/*TO; Animal; Body Water/PH; Bronchial Arteries/*PP; Dogs; Ligation; Pulmonary Circulation; Pulmonary Edema/*ET/PA/PC; Smoke Inhalation Injury/*CO/PA/PP; Support, U.S. Gov't, P.H.S.. .T Bronchial artery ligation modifies pulmonary edema after exposure to smoke with acrolein. .P JOURNAL ARTICLE. .W Pulmonary edema can follow smoke inhalation and is believed to be due to the multiple chemical toxins in smoke, not the heat. We have developed a synthetic smoke composed of aerosolized charcoal particles to which one toxin at a time can be added to determine whether it produces pulmonary edema. Acrolein, a common component of smoke, when added to the synthetic smoke, produced a delayed-onset pulmonary edema in dogs in which the extravascular lung water (EVLW) as detected by a double-indicator technique began to rise after 42 +/- 2 (SE) min from 148 +/- 16 to 376 +/- 60 ml at 165 min after smoke exposure. The resulting pulmonary edema was widespread macroscopically but appeared focal microscopically with fibrin deposits in alveoli adjacent to small bronchi and bronchioles. Bronchial vessels were markedly dilated and congested. Monastral blue B when injected intravenously leaked into the walls of the bronchial vessels down to the region of the small bronchioles (less than or equal to 0.5 mm ID) of acrolein-smoke-exposed dogs but not into the pulmonary vessels. Furthermore, ligation of the bronchial arteries delayed the onset of pulmonary edema (87 +/- 3 min, P less than 0.05) and lessened the magnitude (232 +/- 30 ml, P less than 0.05) at 166 +/- 3 min after acrolein-smoke exposure.(ABSTRACT TRUNCATED AT 250 WORDS) .A Hales CA; Barkin P; Jung W; Quinn D; Lamborghini D; Burke J. .I 201253 .U 90008554 .S J Appl Physiol 9001; 67(3):1007-12 .M Animal; Animals, Newborn; Lung/*IN/PA/PP; Oxygen/*; Pulmonary Surfactants/ME; Respiration, Artificial/*AE; Support, U.S. Gov't, P.H.S.; Swine. .T Lung injury in the neonatal piglet caused by hyperoxia and mechanical ventilation. .P JOURNAL ARTICLE. .W Neonatal lung injury from hyperoxia and mechanical hyperventilation was studied in newborn piglets hyperventilated (arterial PCO2 15-20 Torr) for 24-48 h with 100% O2 and compared with unventilated controls. Pulmonary function testing was performed, and biochemical indicators of lung injury were analyzed from tracheobronchial aspirates at 0, 24, and 48 h. Lung sections were obtained for light and electron microscopy, and bronchoalveolar lavage fluid was analyzed for surfactant composition and activity. At 24 h significant changes in tracheobronchial aspirate albumin concentrations (up 78%) and percent of polymorphonuclear cells (up 16%) were demonstrated. At 48 h a 35% decrease in dynamic lung compliance (P less than 0.05) and a 36% increase in pulmonary resistance (P less than 0.05) were noted. Further biochemical abnormalities occurred with total cell counts increased by 271% (P less than 0.02), albumin 163% (P less than 0.05), total protein 217% (P less than 0.01), and elastase 108% (P less than 0.02). Pathological analyses revealed mild lung injury at 24 h and marked inflammation, abnormal inflation patterns, flattening of Clara cells, fibrinous exudate and edema, early collagen formation, and cell necrosis observed at 48 h. Bronchoalveolar lavage surfactant had normal biophysical activity. Results demonstrate that exposure of neonatal piglets to O2 and mechanical hyperventilation for 48 h cause severe progressive lung injury. .A Davis JM; Penney DP; Notter RH; Metlay L; Dickerson B; Shapiro DL. .I 201254 .U 90008555 .S J Appl Physiol 9001; 67(3):1013-9 .M Airway Resistance/*; Anesthesia; Animal; Cats; Forced Expiratory Flow Rates; Lung Compliance; Lung Volume Measurements; Respiration; Support, Non-U.S. Gov't. .T Flow and volume dependence of expiratory resistance in anesthetized cats. .P JOURNAL ARTICLE. .W In five anesthetized paralyzed cats, mechanically ventilated with tidal volumes of 36-48 ml, the isovolume pressure-flow relationships of the lung and respiratory system were studied. The expiratory pressure was altered between 3 and -12 cmH2O for single tidal expirations. Isovolume pressure-flow plots for three lung volumes showed that the resistive pressure-flow relationships were curvilinear in all cases, fitting Rohrer's equation: P = K1V + K2V2, where P is the resistive pressure loss, K1 and K2 are Rohrer's coefficients, and V is flow. Values of K1 and K2 declined with lung inflation, consistent with the volume dependence of pulmonary (RL) and respiratory system resistances (Rrs). During lung deflation against atmospheric pressure, RL and Rrs tended to remain constant through most of expiration, resulting in a nearly linear volume-flow relationship. In the presence of a fixed respiratory system elastance, the shape of the volume-flow profile depended on the balance between the volume and the flow dependence of RL and Rrs. However, the flow dependence of RL and Rrs indicates that their measured values will be affected by all factors that modify expiratory flow, e.g., respiratory system elastance, equipment resistance, and the presence of respiratory muscle activity. .A Skaburskis M; Shardonofsky F; Milic-Emili J. .I 201255 .U 90008557 .S J Appl Physiol 9001; 67(3):1024-31 .M Adaptation, Physiological; Adolescence; Adult; Airway Obstruction/PP; Airway Resistance; Anesthesia; Female; Human; Lung Compliance/*; Male; Middle Age; Respiration; Scoliosis/*PP; Support, Non-U.S. Gov't; Tidal Volume. .T Respiratory elastic load compensation in anesthetized patients with kyphoscoliosis. .P JOURNAL ARTICLE. .W To evaluate the effects of abnormal respiratory mechanics and neuromuscular drive on the various components of elastic load compensation, we studied 16 anesthetized patients with kyphoscoliosis whose mean passive and active respiratory elastance (Ers and E'rs, respectively), active respiratory resistance, and peak inspiratory occlusion pressure were, respectively, 89, 84, 100, and 37% greater and inspiratory duration (TI) 13% less than corresponding values in 13 anesthetized controls. Ers comprised approximately 66% of effective elastance (E*rs) in both groups. E'rs, reflecting the role of the force-length properties of the active inspiratory muscles in increasing the internal impedance, comprised 83.8 and 86.1% of E*rs in the kyphoscoliosis patients and controls, respectively (P less than 0.001). This demonstrates the influence of increased intrinsic elastance and resistance and decreased TI on tidal volume defense in kyphoscoliosis patients in the absence of vagal modulation. In some patients the difference between Ers and E*rs was substantial, despite an unchanged or even shortened TI, suggesting that the Hering-Breuer reflex may affect stability through ways other than altering TI (e.g., via graded volume-dependent "terminal inhibition"). Characteristics of elastic load compensation in anesthetized kyphoscoliosis patients are similar to those of anesthetized normal subjects. .A Baydur A; Swank SM; Stiles CM; Sassoon CS. .I 201256 .U 90008558 .S J Appl Physiol 9001; 67(3):1032-40 .M Adult; Bronchi/AH/PH; Bronchography; Forced Expiratory Flow Rates; Human; Male; Middle Age; Respiration; Tomography, X-Ray Computed; Trachea/AH/PH/*RA. .T Transverse images of the human thoracic trachea during forced expiration. .P JOURNAL ARTICLE. .W The thoracic trachea and the proximal portion of the major bronchi were imaged in five normal volunteers during a forced expiration maneuver using a cine-computer-tomography system. Sixteen images of two contiguous slices were obtained in less than 1 is while expiratory flow was recorded at the mouth. The area of the thoracic trachea decreased rapidly as flow rate rose to its maximum and the wave of collapse propagated distally. The compressive narrowing of both the pars membranacea and the ventrolateral wall was asymmetric. A contact area appeared between the posterior and the left lateral walls. In one subject the trachea was imaged during the entire maneuver with a lower scan frequency. By 725 ms after the beginning of the forced expiration, the area had first decreased to 15% of its initial value and then reincreased to 46% of its initial value. It stayed constant for the remainder of the maneuver. The measured maximum air velocity was greater than the estimated local wave velocity. .A Thiriet M; Maarek JM; Chartrand DA; Delpuech C; Davis L; Hatzfeld C; Chang HK. .I 201257 .U 90008559 .S J Appl Physiol 9001; 67(3):1041-7 .M Adenosine/ME; Adenosine Diphosphate/ME; Animal; Bronchi/AH/*BS/ME; Dinoprostone/ME; In Vitro; Oligopeptides/ME; Perfusion; Sheep; Support, U.S. Gov't, P.H.S.. .T Metabolic and pharmacokinetic activity of the isolated sheep bronchial circulation. .P JOURNAL ARTICLE. .W We sought to determine bronchial vascular metabolic and pharmacokinetic activity toward benzoyl-Phe-Ala-Pro (BPAP), ADP, adenosine, and prostaglandin E2 (PGE2) by developing an isolated sheep bronchial circulation preparation. We measured mean transit time (t), uptake, and metabolism by injecting 3H-labeled substrates with [14C]sucrose into the bronchial artery of sheep lungs stripped clean of parenchymal tissue. After [3H]BPAP the t for 3H was the same as for 14C. Thirty-six percent of the injected BPAP was converted to metabolite ([3H]benzoyl-Phe) in a single pass. An inhibitor of angiotensin-converting enzyme, SQ 20,881, depressed BPAP metabolism by 50%, while perfusion of the bronchial circulation with glutaraldehyde reduced metabolism to a basal level. After [3H]ADP the t for 3H was again the same as for 14C. 3H recovery after 40 pmol [3H]ADP was less (58%) than after 400 nmol [3H]ADP (79%). Twenty-two percent of the injected radioactivity emerged in the effluent as metabolites of ADP for either dose. Adenosine and PGE2 uptake was negligible, and most of the recovered radioactivity in each case was unchanged substrate. This study suggests that the bronchial circulation is pharmacokinetically and metabolically active with respect to vasoactive mediators like angiotensin I, bradykinin, and adenine nucleotides, and that the enzymes responsible for this metabolic activity line the vascular lumen. .A Grantham CJ; Jackowski JT; Wanner A; Ryan US. .I 201258 .U 90008560 .S J Appl Physiol 9001; 67(3):1048-55 .M Adult; Aged; Dietary Carbohydrates/AD/ME; Dietary Fats/AD/ME; Emphysema/DH/PP/*TH; Exercise; Female; Human; Male; Middle Age; Nutrition Disorders/DH/PP/*TH; Oxidation-Reduction; Oxygen Consumption; Pulmonary Gas Exchange; Respiration. .T Submaximal exercise in emphysema and malnutrition at two levels of carbohydrate and fat intake. .P JOURNAL ARTICLE. .W Eight malnourished patients with emphysema (EMPH) and eight malnourished patients without evidence of lung disease (MLAN) received an infusion of 5% dextrose plus electrolytes (D5W) for 48 h and were then randomly assigned to a hypercaloric diet with either 53% of the calories as carbohydrate (CB) or with 55% as fat (FB) for the 1st wk, maintaining a constant protein intake. The alternate diet was given the following week. Ventilation and gas exchange were measured during supine cycle ergometry at 0, 12, and 25 W during the D5W, CB, and FB diet periods. At each exercise intensity, the EMPH group demonstrated a 12-15% greater O2 consumption, a lower respiratory quotient, and an O2 debt larger than that of the MALN group. Resting ventilation was higher during the CB than FB regimen in both groups of patients, but during the CB diet the EMPH group had a more exaggerated ventilatory response than the MALN group. The results demonstrate that EMPH patients have an unusual metabolic pattern during hypercaloric feeding and exercise. Furthermore in EMPH patients a FB regimen does not appear to create the additional stress on the respiratory system during exercise that is generated with a CB regimen. .A Goldstein SA; Askanazi J; Elwyn DH; Thomashow B; Milic-Emili J; Kvetan V; Weissman C; Kinney JM. .I 201259 .U 90008562 .S J Appl Physiol 9001; 67(3):1063-9 .M Animal; Basement Membrane/CY; Biomechanics; Cell Adhesion; Female; In Vitro; Male; Muscles/*CY/IN; Rana pipiens; Stress, Mechanical; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Tendon Injuries/PA; Tendons/*CY. .T Adhesive strength of single muscle cells to basement membrane at myotendinous junctions. .P JOURNAL ARTICLE. .W Whole muscles loaded to failure frequently fail at or near myotendinous junctions. The present investigation was directed toward determining the breaking stress and failure site of intact and injured myotendinous junction preparations consisting of muscle cells dissected free from surrounding parallel structures but still attached to tendon collagen fibers. These tests show that the breaking stress for intact myotendinous units is 2.7 x 10(5) N/m2, expressed relative to cell cross-sectional area. Failure occurs immediately external to the junction membrane between the cell membrane and lamina densa of the basement membrane. Site and stress at failure are independent of strain and strain rate over a biologically relevant range. Breaking stress in the plane of the membrane, corrected for membrane folding, is 1.2 X 10(4) N/m2. This value is not significantly greater than stress at maximum isometric tension for these cells at these sarcomere lengths. After compression injury, cells fail within the compression site at significantly lower stress (1.9 X 10(5) N/m2). These findings suggest that, in muscle strain injuries that occur under conditions simulated here, failure occurs at myotendinous junctions unless the muscle has suffered previous compression injury leading to failure within the muscle. .A Tidball JG; Chan M. .I 201260 .U 90008566 .S J Appl Physiol 9001; 67(3):1093-9 .M Animal; Anoxemia/BL/*ME/PP; Female; Hemodynamics; Hindlimb; Male; Muscles/*ME; Oxygen/BL/*ME; Rabbits; Skin/BS; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Relationship of venous PO2 to muscle PO2 during hypoxemia. .P JOURNAL ARTICLE. .W Anesthetized mechanically ventilated rabbits were subjected to progressive hypoxemia (n = 7) to determine the relationship of venous PO2 (PvO2) to skeletal muscle PO2 (PtiO2). Measures of arterial PO2 (PaO2), right atrial PO2 [(PvO2)RA], and hindlimb PO2 [(PvO2)limb], were obtained from the carotid artery, right atrium, and inferior vena cava, just above the level of the iliac bifurcation. Biceps femoris muscle PtiO2 was measured with a surface O2 microelectrode having eight measuring points. PaO2 was decreased from 90.3 +/- 5.4 to 26.8 +/- 0.8 Torr in five consecutive steps, followed by reoxygenation to 105.6 +/- 10.5 (SE) Torr. Measurements were obtained after each decrement in PaO2. A total of 128 measures of PtiO2 were obtained per experimental stage. The mean and distribution of the muscle PtiO2 histogram were determined. Measurements were compared with analysis of variance and the Newman-Keuls post hoc method. (PvO2)limb had similar values as the average muscle PtiO2 (PtiO2) for PaO2 values greater than 52.1 +/- 4.3 Torr, where (PvO2)limb became greater than PtiO2 (P less than 0.05). The lowest measures of (PvO2)limb and PtiO2 were 15.9 +/- 0.7 and 4.0 +/- 0.1 Torr, respectively (P less than 0.01). The PtiO2 histograms showed no evidence of increased microvascular heterogeneity with hypoxemia. We conclude that in hypoxemia PvO2 is greater than muscle PtiO2. This difference may be related to the establishment of significant physicochemical O2 gradients from erythrocyte to tissue cell. .A Gutierrez G; Lund N; Acero AL; Marini C. .I 201261 .U 90008567 .S J Appl Physiol 9001; 67(3):1100-5 .M Adolescence; Adult; Bone Density/*; Comparative Study; Hip; Human; Male; Muscles/AH; Physical Fitness; Spine; Sports/*; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Weight Lifting. .T Determinants of bone density among athletes engaged in weight-bearing and non-weight-bearing activity. .P JOURNAL ARTICLE. .W To identify the factors associated with greater bone density among athletic individuals, we recruited three distinct groups of young male subjects. Twenty were nationally ranked water polo players, 19 were engaged in weight-training programs, and 20 subjects comprised a nonexercising comparison group. All participants had measurements of spinal trabecular and integral bone density by quantitative computed tomography as well as a determination of hip bone density by dual photon absorptiometry. A series of potential predictor variables included maximal O2 uptake, back strength, leg strength, total kilocalories expended per day, body mass index, paraspinous muscle cross-sectional area, percent body fat, daily calcium intake, and age. We found no significant differences for any of the bone density measures between the two groups of athletic subjects, whereas bone density was generally significantly lower among the nonexercisers compared with either exercise group. Correlation analysis found only weak and somewhat inconsistent relationships when each of the subgroups was examined separately; however, when all subjects were assessed collectively, many more correlations reached significance. Paraspinous muscular area was found to be most robust in this regard, being significantly correlated with all three bone density measures (r = 0.33-0.55). By using step-wise regression analysis in each subgroup, we observed a consistent significant contribution (R2 = 0.18-0.44) of paraspinous muscle area to the variability in bone density at the spine and the hip. When the data of all three subgroups were pooled, regression analysis reconfirmed the importance of the muscle parameter (R2 = 0.06-0.27) to bone density variation, but more importantly it showed that differentiation based on exercise status was most significant (R2 = 0.18-0.22). .A Block JE; Friedlander AL; Brooks GA; Steiger P; Stubbs HA; Genant HK. .I 201262 .U 90008569 .S J Appl Physiol 9001; 67(3):1113-8 .M Acidosis, Lactic/PP; Animal; Anoxia/PP; Apnea/PP; Chemoreceptors/PH; Electroencephalography; Female; Fetus/*PH; Hypercapnia/PP; Pons/*PH; Pregnancy; Respiration/*; Sheep; Support, Non-U.S. Gov't. .T Lateral pontine lesions affect central chemosensitivity in unanesthetized fetal lambs. .P JOURNAL ARTICLE. .W The mechanisms underlying the apnea associated with both hypoxia and high-voltage electrocortical activity (HV ECOG) in the fetal lamb are not clearly understood. We have previously shown that lesions in the rostral lateral pons change the depressive response to hypoxia to one of stimulation. We now present evidence that lesions in this area also affect the fetal response to H+/CO2. Lactic acidemia and 5-6% hypercapnia both caused almost continuous breathing throughout both HV and low-voltage (LV) ECOG in seven of eight fetuses with lesions that reversed the depressive response to hypoxia. In five intact control fetuses and seven fetuses with lesions that did not affect the response to hypoxia, neither CO2 nor lactic acidemia induced continuous breathing. We conclude that the lateral pontine area, which is involved in the hypoxic depression of breathing in the fetus, is also involved in the inhibitory mechanisms operating during HV ECOG. Furthermore the inhibition of breathing during HV ECOG appears to be related to a raised threshold for fetal breathing, which is sensitive to H+/CO2. .A Johnston BM; Gluckman PD. .I 201263 .U 90008570 .S J Appl Physiol 9001; 67(3):1119-24 .M Adult; Anoxemia/PP; Anoxia/*PP; Arteries; Chemoreceptors/PH; Exercise/*; Human; Male; Oxygen/*BL; Physical Fitness; Respiration/*; Sports. .T Hypoxic ventilatory response and arterial desaturation during heavy work. .P JOURNAL ARTICLE. .W Arterial desaturation in athletes during intense exercise has been reported by several authors, yet the etiology of this phenomenon remains obscure. Inadequate pulmonary ventilation, due to a blunted respiratory drive, has been implicated as a factor. To investigate the relationship between the ventilatory response to hypoxia, exercise ventilation, and arterial desaturation, 12 healthy male subjects [age, 23.8 +/- 3.6 yr; height, 181.6 +/- 5.6 cm; weight, 73.7 +/- 6.2 kg; and maximal O2 uptake (VO2max), 63.0 +/- 2.2 ml.kg-1 min-1] performed a 5-min treadmill test at 100% of VO2max, during which arterial blood samples and ventilatory data were collected every 15 s. Alveolar PO2 (PAO2) was determined using the ideal gas equation. On a separate occasion the ventilatory response to isocapnic hypoxia was measured. Arterial PO2 decreased by an average of 29 Torr during the test, associated with arterial desaturation [arterial O2 saturation (SaO2) 92.0%]. PAO2 was maintained; however, alveolar-arterial gas pressure difference increased progressively to greater than 40 Torr. Minimal hypocapnia was observed, despite marked metabolic acidosis. There was no significant correlation observed between hypoxic drives and ventilation-to-O2 uptake ratio or SaO2 (r = 0.1 and 0.06, respectively, P = NS). These data support the conclusions that hypoxic drives are not related to maximal exercise ventilation or to the development of arterial desaturation during maximal exercise. .A Hopkins SR; McKenzie DC. .I 201264 .U 90008571 .S J Appl Physiol 9001; 67(3):1125-32 .M Acetylcholine/PD; Animal; Comparative Study; Female; Genes, Recessive/*; Linkage (Genetics); Male; Mice; Mice, Inbred Strains; Phenotype; Respiration/*DE; Serotonin/*PD; Species Specificity; Support, Non-U.S. Gov't. .T Autosomal recessive inheritance of airway hyperreactivity to 5-hydroxytryptamine. .P JOURNAL ARTICLE. .W We have previously reported that airway hyperresponsiveness to acetylcholine (ACh) is inherited as an autosomal recessive trait in A/J and C3H/HeJ mice and the progeny of crosses between them (FASEB J. 2: 2605-2608, 1988). In the present report, we have extended these studies by evaluating the biological variability in the airway response to 5-hydroxytryptamine (5-HT) and ACh among multiple genetically standardized inbred strains of mice. The pattern of airway responsiveness to ACh differed significantly from that of 5-HT in nine inbred strains of mice. A/J mice showed nonspecific airway hyperresponsiveness to both 5-HT and ACh. DBA/2J mice were hyperresponsive to 5-HT but not to ACh. An airway phenotype that resembled these inbred strains is termed HYPERREACTIVE. The C3H/HeJ and C57BL/6J inbred strains were minimally reactive to either ACh or 5-HT. Airway phenotypes that resembled these minimally reactive strains are termed HYPOREACTIVE. The frequency of HYPERRACTIVE and HYPOREACTIVE offspring from crosses between A/J and C3H/HeJ mice or DBA/2J and C57BL/6J mice is consistent with a single autosomal recessive gene, primarily determining airway hyperresponsiveness to 5-HT. We report linkage studies which suggest that these genes are not closely linked and that 5-HT and ACh airway hyperresponsiveness is inherited independently. The results of these studies suggest that murine nonspecific airway hyperresponsiveness is determined by multiple genes. .A Levitt RC; Mitzner W. .I 201265 .U 90008572 .S J Appl Physiol 9001; 67(3):1133-9 .M Acetylcholine/PD; Adjuvants, Immunologic; Airway Resistance/DE; Animal; Antigens/*AD; Asthma/*ET; Bordetella pertussis/IM; Disease Models, Animal; Eosinophilia/*ET; Female; Guinea Pigs; Ovalbumin/AD/IM; Passive Cutaneous Anaphylaxis; Support, Non-U.S. Gov't. .T Repeated antigen challenge induces airway hyperresponsiveness with tissue eosinophilia in guinea pigs. .P JOURNAL ARTICLE. .W To test the hypothesis that the development of airway hyperresponsiveness (AHR) lasting greater than or equal to 3 days after the last antigenic exposure required repeated mediator release, we compared dose-response changes in lung resistance (RL) to acetylcholine (ACh) in animals sensitized with 1% ovalbumin (OA), 4% Bordatella pertussis aerosol and subsequently challenged with 0.5% OA aerosol twice weekly for 4-6 wk vs. animals receiving saline aerosol instead of OA. Despite antihistamine pretreatment, each OA challenge produced cyanosis and inspiratory indrawing. Blood gas analysis in six guinea pigs revealed an immediate fall in arterial PO2 (PaO2) from 104.3 +/- 4.9 to 35.4 +/- 2.2 Torr after a 1-min exposure to aerosolized OA. ACh dose-response measurements of RL 3 days after the last OA challenge demonstrated a leftward shift and an increased magnitude of response. These differences were less marked at 7 days, and by 14 days after the last OA challenge, ACh dose-response curves were not different from those of control guinea pigs. Sensitization without repeated antigen challenge did not cause hyperresponsiveness. Morphometric analysis showed significantly increased numbers of eosinophils in the epithelium of airways in hyperresponsive guinea pigs, without neutrophil infiltration or alterations in epithelium and airway wall areas. We conclude that repeated antigenic challenge, but not sensitization alone, causes prolonged AHR in guinea pigs, which is associated with tissue eosinophilia. .A Ishida K; Kelly LJ; Thomson RJ; Beattie LL; Schellenberg RR. .I 201266 .U 90008574 .S J Appl Physiol 9001; 67(3):1150-6 .M Adenosine/AI/PH; Adult; Aminophylline/*PD; Anoxia/DT/*PP; Female; Human; Inspiratory Capacity; Male; Oxygen/*; Respiration/*DE; Support, Non-U.S. Gov't. .T Aminophylline effects on ventilatory response to hypoxia and hyperoxia in normal adults. .P JOURNAL ARTICLE. .W In 10 normal young adults, ventilation was evaluated with and without pretreatment with aminophylline, an adenosine blocker, while they breathed pure O2 1) after breathing room air and 2) after 25 min of isocapnic hypoxia (arterial O2 saturation 80%). With and without aminophylline, 5 min of hyperoxia significantly increased inspiratory minute ventilation (VI) from the normoxic base line. In control experiments, with hypoxia, VI initially increased and then declined to levels that were slightly above the normoxic base line. Pretreatment with aminophylline significantly attenuated the hypoxic ventilatory decline. During transitions to pure O2 (cessation of carotid bodies' output), VI and breathing patterns were analyzed breath by breath with a moving-average technique, searching for nadirs before and after hyperoxia. On placebo days, at the end of hypoxia, hyperoxia produced nadirs that were significantly lower than those observed with room-air breathing and also significantly lower than when hyperoxia followed normoxia, averaging, respectively, 6.41 +/- 0.52, 8.07 +/- 0.32, and 8.04 +/- 0.39 (SE) l/min. This hypoxic depression was due to significant decrease in tidal volume and prolongation of expiratory time. Aminophylline partly prevented these alterations in breathing pattern; significant posthypoxic ventilatory depression was not observed. We conclude that aminophylline attenuated hypoxic central depression of ventilation, although it does not affect hyperoxic steady-state hyperventilation. Adenosine may play a modulatory role in hypoxic but not in hyperoxic ventilation. .A Georgopoulos D; Holtby SG; Berezanski D; Anthonisen NR. .I 201267 .U 90008575 .S J Appl Physiol 9001; 67(3):1157-63 .M Adult; Almitrine/PD; Anoxia/*PP; Chemoreceptors/DE/*PP; Female; Human; Inspiratory Capacity; Male; Respiration/*/DE; Support, Non-U.S. Gov't. .T Increased chemoreceptor output and ventilatory response to sustained hypoxia. .P JOURNAL ARTICLE. .W In adult humans the ventilatory response to sustained hypoxia (VRSH) is biphasic, characterized by an initial brisk increase, due to peripheral chemoreceptor (PC) stimulation, followed by a decline attributed to central depressant action of hypoxia. To study the effects of selective stimulation of PC on the ventilatory response pattern to hypoxia, the VRSH was evaluated after pretreatment with almitrine (A), a PC stimulant. Eight subjects were pretreated with A (75 mg po) or placebo (P) on 2 days in a single-blind manner. Two hours after drug administration, they breathed, in succession, room air (10 min), O2 (5 min), room air (5 min), hypoxia [25 min, arterial O2 saturation (SaO2) = 80%], O2 (5 min), and room air (5 min). End-tidal CO2 was kept constant at the normoxic base-line values. Inspiratory minute ventilation (VI) and breathing patterns were measured over the last 2 min of each period and during minutes 3-5 of hypoxia, and nadirs in VI were assessed just before and after O2 exposure. Independent of the day, the VRSH was biphasic. With P and A pretreatment, early hypoxia increased VI 4.6 +/- 1 and 14.2 +/- 1 (SE) l/min, respectively, from values obtained during the preceding room-air period. On A day the hypoxic ventilatory decline was significantly larger than that on P day, and on both days the decline was a constant fraction of the acute hypoxic response.(ABSTRACT TRUNCATED AT 250 WORDS) .A Georgopoulos D; Walker S; Anthonisen NR. .I 201268 .U 90008576 .S J Appl Physiol 9001; 67(3):1164-70 .M Animal; Dogs; Lung/GD/*PH; Lung Volume Measurements; Maximal Expiratory Flow Rate; Pneumonectomy; Pressure; Support, Non-U.S. Gov't. .T Heterogeneity of maximal lobar emptying rates in dogs with compensatory lung growth. .P JOURNAL ARTICLE. .W Five dogs underwent left pneumonectomy at 10 wk of age, whereas four littermates underwent a sham operation. At 26 wk of age the postpneumonectomy dogs had total lung vital capacity (VC) and lung weight similar to controls, but maximum expiratory flow was reduced. Pressure capsules were glued to right lower (RLL) and right cardiac (RCL) lobes, and alveolar pressures (PA) were measured during forced expiration. In postpneumonectomy dogs RLL and RCL both emptied more slowly than in control dogs, and emptying was especially delayed in RCL, which underwent the most growth. When both lobes deflated together, PA in RCL and RLL were similar in control dogs, but in postpneumonectomy dogs PA in RCL exceeded that in RLL by approximately 3 cmH2O from 80 to 20% VC. Because the higher driving pressure in RCL compensated for the relatively high resistance of RCL, the pattern of lobar emptying was relatively uniform over these lung volumes. This result was compatible with interdependence of lobar maximum expiratory flows. In addition, at PA of 6-10 cmH2O in postpneumonectomy dogs, maximum emptying rates of RCL were less when RCL deflated alone than when RCL and RLL emptied together, again demonstrating interdependence of lobar maximum expiratory flow. .A Mink SN; Holtby SG; Berenzanski DJ; Oppenheimer L; Anthonisen NR. .I 201269 .U 90008577 .S J Appl Physiol 9001; 67(3):1171-8 .M Animal; Anoxia/PP; Cats; Decerebrate State; Efferent Pathways/PH; Female; Hypercapnia/PP; Laryngeal Nerves/*PH; Male; Motor Neurons/PH; Paralysis/PP; Phrenic Nerve/PH; Recurrent Laryngeal Nerve/*PH; Respiration/*; Respiratory Muscles/IR/PH; Support, U.S. Gov't, P.H.S.; Vagus Nerve/PH. .T Respiratory activities of intralaryngeal branches of the recurrent laryngeal nerve. .P JOURNAL ARTICLE. .W To distinguish experimentally between motor nerve activity destined for vocal cord abductor muscles and that bound for muscles that adduct the cords, we recorded efferent activities of intralaryngeal branches of the recurrent laryngeal nerve (RLN) in decerebrate, vagotomized, paralyzed, ventilated cats. Activities of the whole RLN and phrenic nerve were also recorded. Nerve activities were assessed at several steady-state end-tidal O2 and CO2 concentrations. The nerve to the thyroarytenoid (TA) muscle, a vocal cord adductor, was only slightly active under base-line (normocapnic, hyperoxic) conditions but in most cats developed strong activity during expiration in hypocapnia or hypoxia. In severe hypocapnia, phasic expiratory TA activity persisted even during phrenic apnea, indicating continuing activity of the respiratory rhythm generator. The nerve to the posterior cricoarytenoid (PCA) muscle, the vocal cord abductor, was always active in inspiration but often showed expiratory activity as well. This expiratory activity was usually enhanced by hypercapnia and often inhibited by hypoxia. The results are consistent with previous electromyographic findings and emphasize the importance of distinguishing abductor from adductor activity in studies of laryngeal control. .A Zhou D; Huang Q; St. John WM; Bartlett D Jr. .I 201270 .U 90008578 .S J Appl Physiol 9001; 67(3):1179-84 .M Afferent Pathways/PH; Animal; Anoxia/PP; Cats; Decerebrate State; Female; Hypercapnia/PP; Laryngeal Nerves/*PH; Lung Volume Measurements/*; Male; Phrenic Nerve/PH; Recurrent Laryngeal Nerve/*PH; Respiration; Support, U.S. Gov't, P.H.S.; Vagus Nerve/PH. .T Influence of lung volume on activities of branches of the recurrent laryngeal nerve. .P JOURNAL ARTICLE. .W To investigate the influence of inspiratory lung inflation on the respiratory activities of laryngeal motor nerves, vagally intact decerebrate paralyzed cats were ventilated by a servorespirator in accordance with their own phrenic nerve activity. Records were made of the activities of the phrenic nerve, the superior laryngeal nerve (SLN), the recurrent laryngeal nerve (RLN), and the intralaryngeal branches of the RLN serving the thyroarytenoid (TA) and posterior cricoarytenoid (PCA) muscles. Neural activities were assessed in the steady state at different end-tidal O2 and CO2 concentrations. Transient responses to withholding inspiratory lung inflation and to preventing expiratory lung emptying were also studied. Hypercapnia and hypoxia increased the inspiratory activities of the phrenic nerve, SLN, RLN, and its PCA branch. TA inspiratory activity was not changed. Expiratory activities of RLN, PCA, and TA were all increased in hypoxia. When lung inflation was withheld, neural inspiratory duration and the inspiratory activities of all nerves increased. The subsequent period of neural expiration was marked by an exaggerated burst of activity by the TA branch of the RLN. TA expiratory activity was also sharply increased after inspiratory efforts that were reflexly delayed by the prevention of lung emptying. TA activity in expiration was enhanced after vagotomy and was usually more prominent than when lung inflation was withheld before vagal section. The results demonstrate the importance and complexity of the influence of vagal afferents on laryngeal motor activity. .A Huang Q; Zhou D; St. John WM; Bartlett D Jr. .I 201271 .U 90008579 .S J Appl Physiol 9001; 67(3):1185-91 .M Animal; Blood Proteins/*PK; Capillary Permeability/*; Dogs; Hemodynamics; Hypertension/ET; Hypertension, Pulmonary/ET; Intracranial Pressure/*; Lung/*BS; Pulmonary Circulation; Pulmonary Edema/ET; Support, U.S. Gov't, P.H.S.. .T Elevated intracranial pressure increases pulmonary vascular permeability to protein. .P JOURNAL ARTICLE. .W The syndrome of neurogenic pulmonary edema raises the question of whether there are neurological influences on pulmonary vascular permeability. Previous experimental models commonly produced severe hemodynamic alterations, complicating the distinction of increased permeability from increased hydrostatic forces in the formation of the pulmonary edema. Accordingly, we employed a milder central nervous system insult and measured the pulmonary vascular protein extravasation rate, which is a sensitive and specific indicator of altered protein permeability. After elevating intracranial pressure via cisternal saline infusion in anesthetized dogs, we used a dual isotope method to measure the protein leak index. This elevated intracranial pressure resulted in a nearly three-fold rise in the protein leak index (54.1 +/- 7.5 vs. 20.2 +/- 0.9). This central nervous system insult was associated with only mild increases in pulmonary arterial pressures and cardiac output. However, when we reproduced these hemodynamic changes with left atrial balloon inflation or isoproterenol infusion, we observed no effect on the protein leak index compared with control. Although the pulmonary arterial wedge pressure with intracranial pressure remained <10 mmHg, increases in the extravascular lung water were demonstrated. The results suggest the existence of neurological influences on pulmonary vascular protein permeability. We conclude that neurological insults result in increase pulmonary vascular permeability to protein and subsequent edema formation, which could not be accounted for by hemodynamic changes alone. .A McClellan MD; Dauber IM; Weil JV. .I 201272 .U 90008580 .S J Appl Physiol 9001; 67(3):1192-7 .M Human; Infant, Newborn/*PH; Lung Compliance/*; Lung Volume Measurements/*; Respiratory Airflow; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tidal Volume. .T Effect of changes in lung volume on respiratory system compliance in newborn infants. .P JOURNAL ARTICLE. .W Total respiratory system compliance (Crs) at volumes above the tidal volume (VT) was studied by use of the expiratory volume clamping (EVC) technique in 10 healthy sleeping unsedated newborn infants. Flow was measured with a pneumotachograph attached to a face mask and integrated to yield volume. Volume changes were confirmed by respiratory inductance plethysmography. Crs measured by EVC was compared with Crs during tidal breathing determined by the passive flow-volume (PFV) technique. Volume increases of approximately 75% VT were achieved with three to eight inspiratory efforts during expiratory occlusions. Crs above VT was consistently greater than during tidal breathing (P less than 0.0005). This increase in Crs likely reflects recruitment of lung units that are closed or atelectatic in the VT range. Within the VT range, Crs measured by PFV was compared with that obtained by the multiple-occlusion method (MO). PFV yielded greater values of Crs than MO (P less than 0.01). This may be due to braking of expiratory airflow after the release of an occlusion or nonlinearity of Crs. Thus both volume recruitment and airflow retardation may affect the measurement of Crs in unsedated newborn infants. .A Ratjen F; Zinman R; Stark AR; Leszczynski LE; Wohl ME. .I 201273 .U 90008582 .S J Appl Physiol 9001; 67(3):1208-12 .M Adult; Body Temperature; Cold; Epinephrine/BL; Heat/*TU; Human; Hypothermia/PP/*TH; Immersion; Male; Norepinephrine/BL; Radio Waves/*; Shivering; Time Factors. .T Radio frequency (13.56 MHz) energy enhances recovery from mild hypothermia. .P JOURNAL ARTICLE. .W The rate of warming after hypothermia depends on the method of rewarming. This study compared the effectiveness of radio frequency (RF) energy against hot (41 degrees C) water immersion (HW) and an insulated cocoon (IC) for rewarming hypothermic men. Six men fasted overnight and were rewarmed for 1 h after attaining a 0.5 degree C reduction in rectal temperature (Tre). Tre and esophageal (Tes) temperature were recorded every 5 min with nonmetallic thermal probes. The base-line value for Tre and Tes just before rewarming was subtracted from each 5 min Tre and Tes during rewarming to give delta Tre and delta Tes. The 12 delta Tes values were averaged for each individual and were compared using analysis of variance. The average delta Tes for RF (1.15 +/- 0.22 degrees C/h) was faster (P less than 0.001) than either IC (0.37 +/- 0.16 degrees C/h) or HW (0.18 +/- 0.09 degree C/h). The present study shows the superiority of RF energy for rewarming mildly hypothermic men. .A Hesslink RL Jr; Pepper S; Olsen RG; Lewis SB; Homer LD. .I 201274 .U 90008583 .S J Appl Physiol 9001; 67(3):1213-9 .M Airway Resistance; Animal; Bronchi/PH; Dogs; Female; Lung/*PH; Male; Models, Biological; Pressure; Pulmonary Alveoli/PH; Respiratory Airflow/*; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Dynamics of the collateral pathways of canine lungs after flow interruption. .P JOURNAL ARTICLE. .W After interruption of a constant flow (Vcoll) delivered through a bronchoscope into a wedged segment of lung, the pressure at the tip of the bronchoscope (Pb) often decays in a pattern seemingly indicative of two time constants. We tested the hypothesis that the initial more rapid component of the decay is associated with pressure equilibration across the bronchial resistance (Rb), separating bronchoscope tip from alveolus, and that the slower component is associated with pressure equilibration across the collateral pathways separating the wedged segment from surrounding regions. In eight open-chest mongrel dogs, we affixed an alveolar capsule to the segment subtended by the wedged bronchoscope and measured alveolar pressure (PA) and Pb during delivery of Vcoll into the segment and after its sudden interruption. Under both control conditions and after delivery of aerosolized histamine (1.0 or 10 mg/ml), we were unable to demonstrate a gradient between Pb and PA either during constant flow or after flow interruption. Whenever the decay of Pb was not monoexponential, neither was that of PA. Thus there was no evidence of an appreciable Rb, and the rapid component of the decay must be attributable to other factors. In a second protocol, we examined whether behavior departing from monoexponential decay was attributable to the presence of multicompartment behavior within the wedged segment or rather reflected the behavior of a single homogeneous but nonlinear compartment. In five closed-chest dogs, we systematically varied the initial Pb by changing Vcoll and recorded nonexponential pressure decay after flow interruption.(ABSTRACT TRUNCATED AT 250 WORDS) .A Ludwig MS; Bellofiore S; Shore SA; Drazen JM; Fredberg JJ. .I 201275 .U 90008584 .S J Appl Physiol 9001; 67(3):1220-5 .M Aerosols; Airway Resistance/*DE; Animal; Comparative Study; Dogs; Dose-Response Relationship, Drug; Female; Histamine/*AD; Male; Pressure; Pulmonary Alveoli/DE/PH; Support, Non-U.S. Gov't; Trachea/DE/PH. .T A comparison of the dose-response behavior of canine airways and parenchyma. .P JOURNAL ARTICLE. .W We compared the histamine responsiveness of canine airways and parenchymal tissues in six anesthetized paralyzed open-chest mongrel dogs, partitioning total lung resistance (RL) into airway resistance (Raw) and tissue viscance (Vti). Pressure was measured during tidal breathing (frequency was 0.3 Hz) at the trachea and in three alveolar regions by use of alveolar capsules. Measurements were taken before and after the delivery of increasing concentrations of aerosolized histamine (0.1-30 mg/ml). We found that Vti accounted for 78 +/- 8% of RL under base-line conditions; this proportion remained relatively constant throughout the histamine concentration-response curve. There was a significant correlation between percent change in Vti and percent change in Raw at all levels of histamine-induced constriction (P less than 0.001). Moreover, the sensitivity of the tissues and airways (defined as the concentration of histamine required to double resistance) was remarkably similar. We conclude that, at this frequency of ventilation, Vti accounts for the major portion of RL both under base-line conditions and after histamine-induced constriction. Although increases in RL cannot be attributed solely to events occurring in the airways, the close correlation between changes in Raw and Vti and the similar sensitivities of the two support the use of indexes reflecting changes in airway caliber as an indicator of overall lung histamine responsiveness. .A Ludwig MS; Romero PV; Bates JH. .I 201276 .U 90008586 .S J Appl Physiol 9001; 67(3):1234-44 .M Anemia/ME; Animal; Anoxia/ME; Capillaries/ME; Comparative Study; Models, Biological/*; Oxygen/BL/*ME; Oxygen Consumption/*; Oxyhemoglobins/ME; Perfusion; Support, U.S. Gov't, P.H.S.. .T Analysis of oxygen delivery and uptake relationships in the Krogh tissue model. .P JOURNAL ARTICLE. .W Normally, tissue O2 uptake (VO2) is set by metabolic activity rather than O2 delivery (QO2 = blood flow X arterial O2 content). However, when QO2 is reduced below a critical level, VO2 becomes limited by O2 supply. Experiments have shown that a similar critical QO2 exists, regardless of whether O2 supply is reduced by progressive anemia, hypoxemia, or reduction in blood flow. This appears inconsistent with the hypothesis that O2 supply limitation must occur by diffusion limitation, since very different mixed venous PO2 values have been seen at the critical point with hypoxic vs. anemic hypoxia. The present study sought to begin clarifying this paradox by studying the theoretical relationship between tissue O2 supply and uptake in the Krogh tissue cylinder model. Steady-state O2 uptake was computed as O2 delivery to tissue representative of whole body was gradually lowered by anemic, hypoxic, or stagnant hypoxia. As diffusion began to limit uptake, the fall in VO2 was computed numerically, yielding a relationship between QO2 and VO2 in both supply-independent and O2 supply-dependent regions. This analysis predicted a similar biphasic relationship between QO2 and VO2 and a linear fall in VO2 at O2 deliveries below a critical point for all three forms of hypoxia, as long as intercapillary distances were less than or equal to 80 microns. However, the analysis also predicted that O2 extraction at the critical point should exceed 90%, whereas real tissues typically extract only 65-75% at that point. When intercapillary distances were larger than approximately 80 microns, critical O2 extraction ratios in the range of 65-75% could be predicted, but the critical point became highly sensitive to the type of hypoxia imposed, contrary to experimental findings. Predicted gas exchange in accord with real data could only be simulated when a postulated 30% functional peripheral O2 shunt (arterial admixture) was combined with a tissue composed of Krogh cylinders with intercapillary distances of less than or equal to 80 microns. The unrealistic efficacy of tissue O2 extraction predicted by the Krogh model (in the absence of postulated shunt) may be a consequence of the assumed homogeneity of tissues, because real tissues exhibit many forms of heterogeneity among capillary units. Alternatively, the failure of the original Krogh model to fully predict tissue O2 supply dependency may arise from basic limitations in the assumptions of that model. .A Schumacker PT; Samsel RW. .I 201277 .U 90008587 .S J Appl Physiol 9001; 67(3):1245-9 .M Adult; Alkalosis/PP; Electromyography; Exercise/*; Fatigue/PP; Human; Hydrogen-Ion Concentration; Lactates/ME; Male; Muscle Contraction; Muscles/*PH; Support, Non-U.S. Gov't. .T Surface EMG power spectrum and intramuscular pH in human vastus lateralis muscle during dynamic exercise. .P JOURNAL ARTICLE. .W The relationship between intramuscular pH and the frequency components of the surface electromyographic (EMG) power spectrum from the vastus lateralis muscle was studied in eight healthy male subjects during brief dynamic exercise. The studies were carried out in placebo control and metabolic alkalosis induced by oral administration of NaHCO3. At the onset of exercise, blood pH was 0.08 units higher in alkalosis compared with placebo. Muscle lactate accumulation during exercise was higher in alkalosis (32 +/- 5 mmol/kg wet wt) than in placebo (17 +/- 4 mmol/kg wet wt), but no difference in intramuscular pH was found between the two conditions. The EMG power spectrum was shifted toward lower frequencies during fatigue in the control condition (10.1 +/- 0.9%), and these spectral shifts, evaluated from changes in the mean power frequency (MPF) of the EMG power spectrum, were further accentuated in alkalosis (19 +/- 2%). Although the changes in frequency components of EMG correlated with muscle lactate accumulation (r = 0.68, P less than 0.01), no direct relationship with muscle pH was observed. We conclude that alkalosis results in a greater reduction in MPF associated with a higher muscle lactate accumulation. However, the good correlation observed between the two variables is not likely causative, and a dissociation between intramuscular pH and the increase in the low-frequency content of EMG power spectrum appears during muscle fatigue. .A Bouissou P; Estrade PY; Goubel F; Guezennec CY; Serrurier B. .I 201278 .U 90008588 .S J Appl Physiol 9001; 67(3):1250-5 .M Adenosine Diphosphate/PD; Diving/AE; Gases/*BL; Human; Hydrogen-Ion Concentration; Hydrostatic Pressure; In Vitro; Male; Platelet Aggregation/*/DE; Stress, Mechanical; Support, Non-U.S. Gov't. .T Effects of gas bubbling and other forms of convection on platelets in vitro. .P JOURNAL ARTICLE. .W Citrated platelet-rich human plasma was subjected to one of three experimental treatments at 37 degrees C for 15 min: stirring, bubbling (with stirring), and gentle agitation achieved by a rocking motion. The last two were "equiconvective" as judged by equilibration rates with CO2 and O2 but presumably differed in the shear stress they imposed on the cells. Stirring platelets in normal air or 5% CO2-air caused no significant aggregation. Bubbling air through platelet-rich plasma increased its pH and marked aggregation occurred. Bubbling CO2-air caused the platelet-rich plasma pH to attain its physiological level of 7.4 with less aggregation. In both cases, subsequent ADP-induced aggregation was diminished. Rocking (without stirring) in the presence of CO2-air caused negligible aggregation in platelets and an enhanced response to ADP. Because of the marked difference between the two equiconvective treatments, bubbling and rocking, the main factor in activating the human platelets is suggested to be shear stress (potentiated by high pH), with perhaps a lesser contribution from the air-plasma interface. .A Pickles DM; Ogston D; MacDonald AG. .I 201279 .U 90008589 .S J Appl Physiol 9001; 67(3):1256-64 .M Age Factors; Animal; Antigens, Helminth/*AD; Ascaris/IM; Asthma/PP; Comparative Study; Female; Indomethacin/PD; Male; Muscle Contraction/DE; Pyrilamine/PD; Sheep; Support, Non-U.S. Gov't; Trachea/*BS/PH; Vasoconstriction/DE. .T Effects of antigen on tracheal circulation and smooth muscle in sheep of different ages. .P JOURNAL ARTICLE. .W The effects of Ascaris suum antigen on tracheal circulation and tracheal smooth muscle tone were compared in two groups of sheep: the first group was 1 yr old (14 sheep) and the second 5 yr old (8 sheep). Cranial tracheal arteries of anesthetized and paralyzed sheep were perfused at constant flow with monitoring of perfusion pressure. Tracheal smooth muscle tone was assessed by measuring changes in the external diameter of the cranial trachea. Close-arterial injection of antigen (1-20 micrograms) in young sheep produced dose-dependent vasodilation (6.1-15.5% fall in perfusion pressure) and smooth muscle contraction (0.06-0.28 mm reduction in tracheal diam). In old sheep, antigen (1-20 micrograms) produced vasoconstriction (4.1-16.8%) but no smooth muscle response. The smooth muscle contraction in young sheep was blocked by mepyramine (2 mg/kg iv) suggesting mediation by release of histamine. The vasodilation in young sheep and the vasoconstriction in old sheep were reduced by indomethacin (5 mg/kg iv), and the residual response was further reduced by FPL 55712 (2 mg/kg iv), suggesting mediation by both cyclooxygenase products and leukotrienes. Thus antigen given in the tracheal vasculature releases a mixture of inflammatory mediators. This mixture of mediators or their actions on the tracheal vasculature and smooth muscle may depend on the age of the sheep. .A Webber SE; Salonen RO; Deffebach ME; Widdicombe JG. .I 201280 .U 90008590 .S J Appl Physiol 9001; 67(3):1265-70 .M Adult; Aged; Calcitonin Gene-Related Peptide/*PD/PH; Endothelium, Vascular/DE/PH; Human; In Vitro; Middle Age; Muscle, Smooth, Vascular/DE/PH; Pulmonary Artery/AH/DE/PH; Pulmonary Circulation/*DE; Pulmonary Veins/AH/DE/PH; Receptors, Endogenous Substances/PH; Support, Non-U.S. Gov't; Vasodilation/*DE. .T Calcitonin gene-related peptide vasodilation of human pulmonary vessels. .P JOURNAL ARTICLE. .W Human calcitonin gene-related peptide (CGRP) is localized to sensory neurons in pulmonary vessels and is a potent vasodilator. We have characterized the effects of CGRP in human pulmonary vessels and localized the receptors for this peptide by autoradiography. Fresh human lung tissue was obtained from eight patients undergoing surgery and small (200-400 microns ID) pulmonary arteries and veins were dissected free of surrounding connective and pulmonary tissue. Pairs of vessels were studied and in one of each pair the endothelium was left intact and from the other of each pair the endothelium was removed by gentle abrasion. For functional studies arteries (n = 9) and veins (n = 9) were suspended in an organ bath, precontracted with 1 microM prostaglandin F2 alpha. CGRP (10 pM to 10 microM) was added in a cumulative manner. CGRP caused a dose-dependent relaxation of endothelium intact human pulmonary arteries and veins with log EC50 values of -8.01 +/- 0.35 and -8.70 +/- 0.40, respectively (not significant). Removal of the endothelium did not diminish the vasodilator potency of CGRP in either vessel. For autoradiographic studies, cryostat sections of the small human pulmonary vessels with or without endothelium were used. 125I-CGRP densely labeled CGRP receptors on vascular smooth muscle and endothelial removal did not have any effect on grain density. We concluded that CGRP is a potent vasodilator of human pulmonary arteries and veins that is not dependent on an intact endothelium. These functional studies correlate with the distribution of CGRP receptors as localized by autoradiography. .A McCormack DG; Mak JC; Coupe MO; Barnes PJ. .I 201281 .U 90008592 .S J Appl Physiol 9001; 67(3):1277-85 .M Animal; Blood Pressure/*; Blood Pressure Determination/MT; Catheterization; Comparative Study; Dogs; Female; Histamine/PD; Male; Pulmonary Artery/PH; Pulmonary Circulation/*/DE; Pulmonary Veins/PH; Punctures; Serotonin/PD; Support, Non-U.S. Gov't; Vascular Resistance. .T Occlusion pressures vs. micropipette pressures in the pulmonary circulation. .P JOURNAL ARTICLE. .W Because of the discrepancies between the arterial and venous occlusion technique and the micropuncture technique in estimating pulmonary capillary pressure gradient, we compared measurements made with the two techniques in the same preparations (isolated left lower lobe of dog lung). In addition, we also obtained direct and reliable measurements of pressures in 0.9-mm arteries and veins using a retrograde catheterization technique, as well as a microvascular pressure made with the double-occlusion technique. The following conclusions were made from dog lobes perfused with autologous blood at normal flow rate of 500-600 ml/min and pressure gradient of 12 mmHg. 1) The double-occlusion technique measures pressure in the capillaries, 2) a small pressure gradient (0.5 mmHg) exists between 30- to 50-micron arteries and veins, 3) a large pressure gradient occurs in arteries and veins greater than 0.9 mm, 4) the arterial and venous occlusion techniques measure pressures in vessels that are less than 900 microns diam but greater than 50 microns, very likely close to 100 microns, 5) serotonin constricts arteries (larger and smaller than 0.9 mm) whereas histamine constricts veins (larger and smaller than 0.9 mm). Thus three different techniques (small retrograde catheter, arterial and venous occlusion, and micropuncture) show consistent results, confirming the presence of significant resistance in large arteries and veins with minimal resistance in the microcirculation. .A Hakim TS; Kelly S. .I 201282 .U 90008593 .S J Appl Physiol 9001; 67(3):1286-93 .M Animal; Animals, Newborn; Body Water/*PH; Female; Fluoroscopy; In Vitro; Lung/*PH/RA; Pregnancy; Radiographic Image Enhancement; Respiration/*; Sheep. .T Measurement of lung water dynamics and lung aeration in the perinatal period by use of digital X-ray fluoroscopy. .P JOURNAL ARTICLE. .W A method has been developed for the measurement of lung water dynamics and regional aeration of the lung in anesthetized newborn lambs by use of X-ray fluoroscopy, video recording, and digital image processing. After cesarean section and before the first breath fetal lambs under halothane-oxygen were placed on an X-ray table and connected to a volume-cycled respirator. X-ray fluoroscopy commenced before the initiation of respiration, and the images were recorded on video tape. X-ray transmission through the thorax increased as the lung was aerated. The enhanced transmission was compared with the values obtained from a calibration water wedge from which an equivalent path length through water can be estimated. In testing this method, it was demonstrated that X-ray transmission was linearly related to the wet lung weight-to-body weight ratio and to the product of the wet-to-dry weight ratio multiplied by anatomic thickness of frozen lung blocks. Calibrated values were also linearly related to this product and to the actual measured height of the fluid and tissue in the fluid-filled lung. .A Maloney JE; Takahashi Y; Kondo C; Schoel WM. .I 201283 .U 90008594 .S J Appl Physiol 9001; 67(3):1294-8 .M Acetylcholine/PD; Animal; Dogs; In Vitro; Isoproterenol/PD; McN A 343/PD; Muscle Contraction/DE; Muscle, Smooth/DE/PH; Parasympathomimetics/PD; Piperidines/PD; Pirenzepine/PD; Receptors, Adrenergic, Beta/DE/*PH; Receptors, Muscarinic/DE/*PH; Support, U.S. Gov't, P.H.S.; Trachea/DE/*PH. .T Muscarinic receptor reserve and beta-adrenergic sensitivity in tracheal smooth muscle. .P JOURNAL ARTICLE. .W The possibility that differences in beta-adrenergic sensitivity among canine trachealis muscles contracted with different contractile agonists are related to differences in the receptor-occupancy characteristics of the contractile agonists was investigated. Relaxation to isoproterenol was compared in muscles contracted with the muscarinic agonists McN-A-343 and acetylcholine (ACh). The apparent dissociation constant (pKB) values for the M1-antagonist, pirenzepine, against ACh (6.96 +/- 0.18) and McN-A-343 (6.84 +/- 0.08) were similar. The pKB values for the M3-antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) against ACh (8.76 +/- 0.13) and McN-A-343 (8.71 +/- 0.10) were also similar, suggesting that these agonists were activating the same subtype of muscarinic receptor, probably M3. However, the contractile response to ACh was associated with a greater receptor reserve than that for McN-A-343. Isoproterenol relaxed muscles contracted with McN-A-343 much more effectively than those contracted with an equieffective concentration of ACh. The results suggest that the relative resistance of ACh-induced contractions to relaxation by isoproterenol may not be an inherent quality of muscarinic receptor stimulation. The large receptor reserve available to ACh may act to buffer the contractile response from the inhibitory effects of beta-adrenergic stimulation. Alternatively, ACh may be able to initiate subcellular mechanisms that are unavailable to agonists of lower efficacy. .A Gunst SJ; Stropp JQ; Flavahan NA. .I 201284 .U 90008595 .S J Appl Physiol 9001; 67(3):1299-300 .M Adult; Aged; Aged, 80 and over; Aging/PH; Cardiac Output; Human; Middle Age; Muscles/AH; Oxygen Consumption/*. .T VO2max limits [letter; comment] .P COMMENT; LETTER. .A Booth FW. .I 201285 .U 90008597 .S J Appl Physiol 9001; 67(3):926-32 .M Female; Human; Male; Muscles/*ME; Nuclear Magnetic Resonance; Phosphates/ME; Phosphocreatine/ME; Physical Education and Training; Physical Endurance; Sports/*; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Wrist. .T Wrist flexor muscles of elite rowers measured with magnetic resonance spectroscopy. .P JOURNAL ARTICLE. .W We used phosphorus magnetic resonance spectroscopy to study skeletal muscle metabolism of trained vs. untrained humans. The forearms of highly trained rowers (n = 10) and age-matched controls were placed in a 1.9-T magnet so that the wrist flexor muscles were placed over a 4-cm transmitting and receiving coil. The subjects performed work by depressing a handle attached to an isokinetic ergometer. Relative concentrations of Pi, phosphocreatine (PCr), and ATP were measured along with intracellular pH. Measurements were made at rest, during steady-state and ramp exercise protocols, and during recovery from exercise. At rest the rowers had Pi/PCr that were not different from control. During steady-state exercise rowers (n = 4) had lower Pi/PCr at the same relative power levels, and the slope of the power vs. Pi-PCr curve was significantly greater than for controls. Rowers (n = 4) also had faster rates of PCr recovery after exercise than controls (T1/2 of 24 +/- 2.0 s for rowers and 47 +/- 8.4 s for controls) when power level was adjusted so that all subjects recovered from the same level of Pi/PCr. During a ramp exercise protocol, the initial slope of the power vs. Pi-PCr curve was greater in three of six rowers compared with controls and at the highest power level rowers had lower Pi/PCr values with less drop in pH. At the end of the ramp test, the same degree of muscle fatigue was associated with much lower levels of H2PO-4 (5.7 +/- 0.70 mM) in rowers compared with controls (13.0 +/- 1.8 mM).(ABSTRACT TRUNCATED AT 250 WORDS) .A McCully KK; Boden BP; Tuchler M; Fountain MR; Chance B. .I 201286 .U 90008598 .S J Appl Physiol 9001; 67(3):933-7 .M Adult; Airway Resistance/*; Comparative Study; Evaluation Studies; Female; Human; Lung Diseases, Obstructive/DI/PP; Male; Methods; Middle Age; Plethysmography, Whole Body. .T Reassessment of the interruption technique for measuring flow resistance in humans. .P JOURNAL ARTICLE. .W We have previously produced evidence that, in patients with obstructive lung disease, compliance of extrathoracic airways is responsible for lack of mouth-to-alveolar pressure equilibration during respiratory efforts against a closed airway. The flow interruption method for measuring respiratory resistance (Rint) is potentially faced with the same problems. We reassessed the merits of the interruption technique by rendering the extrathoracic airways more rigid and by using a rapid shutter. We measured airway resistance (Raw) with whole body plethysmography during panting (at 2 Hz) and Rint during quiet breathing. Rint and Raw were expressed as specific airway (sGaw) and interruptive conductance (sGint), respectively. In nine healthy subjects (cheeks supported), sGint (0.140 +/- 0.050 s-1.cmH2O-1) was lower (P less than 0.02) than sGaw (0.182 +/- 0.043 s-1.cmH2O-1). By contrast, in 12 patients with severe obstructive lung disease (forced expiratory volume in 1 s/vital capacity = 41.0 +/- 19.8%), sGint (0.058 +/- 0.012 s-1.cmH2O-1) was higher (P less than 0.05) than sGaw (0.047 +/- 0.007 s-1.cmH2O-1), when the cheeks were supported. When the mouth floor was also supported, average values of sGaw (0.048 +/- 0.008 s-1.cmH2O-1) and sGint (0.049 +/- 0.014 s-1.cmH2O-1) became similar. In conclusion, we confirm previous findings in healthy subjects of higher values of Rint, with respect to Raw, probably because of differences in glottis opening between quiet breathing and panting. In airflow obstruction, supporting both the cheeks and the mouth floor decreased sGint, which became similar to sGaw. .A Liistro G; Stanescu D; Rodenstein D; Veriter C. .I 201287 .U 90008600 .S J Appl Physiol 9001; 67(3):945-53 .M Adaptation, Physiological; Adenosine Triphosphatase/ME; Animal; Glycerolphosphate Dehydrogenase/ME; Male; Muscle Contraction; Muscles/AH/*PH; Muscular Atrophy/PC; Physical Conditioning, Animal; Rats; Rats, Inbred Strains; Succinate Dehydrogenase/ME; Support, U.S. Gov't, Non-P.H.S.. .T Effects of periodic weight support on medial gastrocnemius fibers of suspended rat. .P JOURNAL ARTICLE. .W Based on the current view that muscle fiber types reflect, at least to some degree, the probability of excitation of motor units in most normal movements, it was hypothesized that brief moderate periods of weight support would have little effect on a muscle that consists predominantly of high-threshold motor units. To test this hypothesis, the effects of 7 days of hindlimb suspension (HS) and HS plus intermittent weight support activity on the size and metabolic properties of individual fibers in the medial gastrocnemius (MG) were studied. HS resulted in a 40% decrease in the mean cross-sectional area of fibers that stain either dark or light for myosin adenosinetriphosphatase (ATPase) at an alkaline preincubation and are located in the deep region (i.e., close to the bone) of the MG. Dark ATPase fibers located in the superficial region were 17% smaller than controls (P greater than 0.05). Although the mean succinate and alpha-glycerophosphate dehydrogenase activities (optical density/min) per muscle fiber were not significantly (P greater than 0.05) affected by HS, it appeared that selected fibers of the deep MG region of HS rats had elevated enzyme activities. HS plus walking on a treadmill for 10 min every 6 h at 5 m/min and at a 19 degrees incline (total of 40 min/day) resulted in mean fiber cross-sectional area and enzyme activities nearer to control than the HS values. All adaptations were much less obvious in the fibers in a superficial (i.e., away from the bone) MG region.(ABSTRACT TRUNCATED AT 250 WORDS) .A Graham SC; Roy RR; Hauschka EO; Edgerton VR. .I 201288 .U 90008602 .S J Appl Physiol 9001; 67(3):959-62 .M Animal; Cell Count; Cell Movement/DE; Dogs; Eosinophilia/*CI/PA; Prostaglandin D2/*PD; Receptors, Prostaglandin/DE; Sulfonamides/PD; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Trachea/*DE/PA. .T Prostaglandin D2 causes accumulation of eosinophils in the lumen of the dog trachea. .P JOURNAL ARTICLE. .W Prostaglandin D2 (PGD2), the major product of arachidonic acid metabolism via the cyclooxygenase pathway in most mast cells, is present in the airways of atopic asthmatic patients after antigen challenge. Because eosinophilia is characteristic of asthma, we asked whether PGD2 causes eosinophils to accumulate in the airways in vivo. Using an endotracheal tube with two inflatable balloons we isolated a segment of trachea in four anesthetized mechanically ventilated dogs, and we superfused this segment with either a control solution (Hanks' balanced salt solution and antibiotics) or solution containing PGD2 (10(-6) M). Total and differential cell counts were determined at base line and every hour for 4 h during the study. PGD2 caused eosinophil accumulation in the trachea [7.0 +/- 3.4, 28.7 +/- 17.8, 33.7 +/- 13.6, and 35.4 +/- 10.7 (SD) cells/cm2 trachea after 1, 2, 3, and 4 h, respectively, P less than 0.05 vs. controls] but had no significant effect on neutrophil accumulation. The effect of PGD2 on eosinophil accumulation was significantly inhibited by the prostaglandin receptor antagonist SKF 88046 (5 mg/kg iv). We conclude that PGD2 is a selective stimulus that causes accumulation of eosinophils in the tracheal lumen of dogs in vivo. .A Emery DL; Djokic TD; Graf PD; Nadel JA. .I 201289 .U 90008603 .S J Appl Physiol 9001; 67(3):963-9 .M Animal; Body Temperature Regulation/DE; Dinoprostone/PD; Endotoxins/AD/*TO; Fever/*CI/PP; Injections, Intravenous; Interleukin-1/PD; Lipopolysaccharides/AD/TO; Male; Pyrogens/PD; Rats; Rats, Inbred Strains; Starvation. .T Blunted febrile response to intravenous endotoxin in starved rats. .P JOURNAL ARTICLE. .W The effects of fasting on the febrile responses to intravenous injection of bacterial lipopolysaccharide (LPS; endotoxin) of Escherichia coli were investigated in rats. Ad libitum-fed rats (C) produced a biphasic fever with an increase in the temperature difference between brown adipose tissue and colon and shivering activity (SA). Measurement by a direct calorimeter showed no particular changes in heat loss. Rats starved for 4 days (F4) responded to intravenous LPS with a monophasic fever accompanied by an increase in SA only. However the maximal rise in colonic temperature (Tco) did not differ from C rats. Subsequent 2-day fasting reduced SA and the maximal fever height. Endogenous pyrogen (EP) injected intravenously produced a prompt rise in Tco followed by prolonged hyperthermia in C rats. In the F4 rats, there was no such sustained rise in Tco as a result of intravenous EP. The response in Tco to intravenous prostaglandin E2 (PGE2) was the same in fed and starved rats. The administration of LPS, EP, and PGE2 into the lateral ventricle evoked a similar extent of hyperthermia in C and F4 rats. Because the second phase of fever has been shown to occur after pyrogens are translated into a febrile stimulus within the blood-brain barrier, it is assumed that the functional changes of the blood-brain barrier such as in the permeability of pyrogens or in the sensitivity of pyrogen receptors resulted in the absence of the second phase of fever in starved rats. .A Shido O; Nagasaka T; Watanabe T. .I 201290 .U 90008606 .S J Appl Physiol 9001; 67(3):980-4 .M Adult; Fatigue/PP/*PX; Human; Male; Muscle Contraction/*; Neuropsychology; Psychophysiology; Support, Non-U.S. Gov't; Sympathetic Nervous System/*PP. .T Sympathetic nerve activity related to local fatigue sensation during static contraction. .P JOURNAL ARTICLE. .W The relationship between autonomic nervous activity and psychophysical responses was studied during static exercise in humans. Muscle sympathetic nerve activity (MSNA) recorded by a direct method of microneurography and the intensity of fatigue sensation in working muscles [levels of fatigue sensation (LFS) scale 0-10] were analyzed in 11 male subjects during static handgrip (SHG). SHG was exerted at a tension of 25% of maximal voluntary contraction until the given tension could no longer be sustained. MSNA, represented as total activity (burst number x mean burst amplitude), and LFS increased in a time-dependent process till the end of the SHG. At the termination of the static exercise MSNA had increased an average of 480% of the resting value. In the simple exponential curve, Y = A expBX, where X was LFS and Y was MSNA. The constants A and B estimated from the total experiments were 84.5 and 0.161, respectively. The correlation between LFS and MSNA was statistically significant. There was a large difference in the value of constant B (0.089-0.278) among the subjects, and a relatively small difference in the value of constant A (37.5-133.8). The increases in both MSNA and LFS during SHG may be mainly related to the same afferent volley from working skeletal muscles. The results indicate that the response of the muscle sympathetic nerve to SHG relates to the psychological feelings of fatigue in the working muscles. .A Saito M; Mano T; Iwase S. .I 201291 .U 90008607 .S J Appl Physiol 9001; 67(3):985-92 .M Animal; Comparative Study; Dogs; High-Frequency Ventilation/*MT; Lung/*PH; Lung Compliance; Pressure; Pulmonary Gas Exchange/*; Respiration, Artificial; Respiratory System; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Thorax; Tidal Volume. .T Lung pressures and gas transport during high-frequency airway and chest wall oscillation. .P JOURNAL ARTICLE. .W The major goal of this study was to compare gas exchange, tidal volume (VT), and dynamic lung pressures resulting from high-frequency airway oscillation (HFAO) with the corresponding effects in high-frequency chest wall oscillation (HFCWO). Eight anesthetized paralyzed dogs were maintained eucapnic with HFAO and HFCWO at frequencies ranging from 1 to 16 Hz in the former and 0.5 to 8 Hz in the latter. Tracheal (delta Ptr) and esophageal (delta Pes) pressure swings, VT, and arterial blood gases were measured in addition to respiratory impedance and static pressure-volume curves. Mean positive pressure (25-30 cmH2O) in the chest cuff associated with HFCWO generation decreased lung volume by approximately 200 ml and increased pulmonary impedance significantly. Aside from this decrease in functional residual capacity (FRC), no change in lung volume occurred as a result of dynamic factors during the course of HFCWO application. With HFAO, a small degree of hyperinflation occurred only at 16 Hz. Arterial PO2 decreased by 5 Torr on average during HFCWO. VT decreased with increasing frequency in both cases, but VT during HFCWO was smaller over the range of frequencies compared with HFAO. delta Pes and delta Ptr between 1 and 8 Hz were lower than the corresponding pressure swings obtained with conventional mechanical ventilation (CMV) applied at 0.25 Hz. delta Pes was minimized at 1 Hz during HFCWO; however, delta Ptr decreased continuously with decreasing frequency and, below 2 Hz, became progressively smaller than the corresponding values obtained with HFAO and CMV. .A Khoo MC; Ye TH; Tran NH. .I 201292 .U 90008608 .S J Appl Physiol 9001; 67(3):993-1000 .M Airway Resistance; Biomechanics; Comparative Study; High-Frequency Ventilation/*MT; Human; Lung/*PH; Lung Compliance; Models, Biological/*; Pressure; Pulmonary Gas Exchange; Respiration; Respiratory System; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Thorax. .T Minimization of lung pressure swings during high-frequency ventilation: a model. .P JOURNAL ARTICLE. .W The goal of this theoretical study was to develop a simple computational model for determining the lung pressure excursions that accompany the maintenance of adequate gas transport through high-frequency airway oscillations applied via the trachea (HFAO) and by transthoracic means (HFTO). Respiratory mechanics and gas transport parameters estimated from the preceding companion study (J. Appl. Physiol. 67: 985-992, 1989) were used in the model for computing tracheal, alveolar, pleural, and transpulmonary pressure swings. Comparison of model predictions with corresponding data obtained in dogs showed close agreement. The specification of eucapnia as a constraint led to results that were significantly different from previous findings which had assumed constant airflow. We used the model to identify "quasi-optimal" strategies for HFAO and HFTO application in which all pressure excursions were kept below the corresponding levels produced by conventional mechanical ventilation operating at 15 breaths/min. The model suggests the application of both HFAO and HFTO at frequencies substantially lower than the settings commonly employed in high-frequency ventilation. Application of HFAO at frequencies ranging from 1 to 4 Hz is recommended, whereas for HFTO the quasi-optimal range lies between 1 and 1.7 Hz. In patients with chronic obstructive pulmonary disease, pressure costs during HFAO or HFTO are minimized in the vicinity of 1 Hz. .A Khoo MC; Yamashiro SM; Yamashiro P. .I 201293 .U 90008610 .S J Appl Physiol 9001; 67(4):1319-22 .M Adult; Epinephrine/*BL; Exercise/*PH; Human; Lactates/*BL; Male; Norepinephrine/*BL; Oxygen Consumption/PH. .T Influence of plasma catecholamines on the lactate threshold during graded exercise. .P JOURNAL ARTICLE. .W This investigation examined the relationship among plasma catecholamines, the blood lactate threshold (TLa), and the ventilatory threshold (TVE) in highly trained endurance athletes. Six competitive cyclists and six varsity cross-country runners performed a graded exercise test via two different modalities: treadmill running and bicycle ergometry. Although maximal oxygen consumption (VO2 max) did not differ significantly for the cyclists for treadmill running and cycling (64.6 +/- 1.0 and 63.5 +/- 0.4 ml O2.kg-1-min-1, respectively), both TLa and TVE occurred at a relatively earlier work load during the treadmill run. The opposite was true for the runners as TLa and TVE appeared at an earlier percent of VO2max during cycling compared with treadmill running (60.0 +/- 1.7 vs. 75.0 +/- 4.0%, respectively, TLa). The inflection in plasma epinephrine shifted in an identical manner and occurred simultaneously with that of TLa (r = 0.97) regardless of the testing protocol or training status. Although a high correlation (r = 0.86) existed for the shift in TVE and TLa, this relationship was not as strong as was seen with plasma epinephrine. The results suggest that a causal relationship existed between the inflection in plasma epinephrine and TLa during a graded exercise test. This association was not as strong for TVE and TLa. .A Mazzeo RS; Marshall P. .I 201294 .U 90008611 .S J Appl Physiol 9001; 67(4):1323-30 .M Albumins/*ME; Animal; DTPA; Extracellular Space/*ME; Female; Iodine Radioisotopes; Lung/*ME; Lymph/PH; Male; Sheep; Support, U.S. Gov't, P.H.S.; Technetium. .T Measurement of lung fluid volumes and albumin exclusion in sheep. .P JOURNAL ARTICLE. .W A radioactive tracer technique was used to determine interstitial diethylenetriaminepentaacetic acid (DTPA) and albumin distribution volume in sheep lungs. 125I- and/or 131I-labeled albumin were injected intravenously and allowed to equilibrate for 24 h. 99mTc-labeled DTPA and 51Cr-labeled erythrocytes were injected and allowed to equilibrate (2 h and 15 min, respectively) before a lethal dose of thiamylal sodium. Two biopsies (1-3 g) were taken from each lung and the remaining tissue was homogenized for wet-to-dry lung weight and volume calculations. Estimates of distribution volumes from whole lung homogenized samples were statistically smaller than biopsy samples for extravascular water, interstitial 99mTc-DTPA, and interstitial albumin. The mean fraction of the interstitium (Fe), which excludes albumin, was 0.68 +/- 0.04 for whole lung samples compared with 0.62 +/- 0.03 for biopsy samples. Hematocrit may explain the consistent difference. To make the Fe for biopsy samples match that for homogenized samples, a mean hematocrit, which was 82% of large vessel hematocrit, was required. Excluded volume fraction for exogenous sheep albumin was compared with that of exogenous human albumin in two sheep, and no difference was found at 24 h. .A Pou NA; Roselli RJ; Parker RE; Clanton JA; Harris TR. .I 201295 .U 90008612 .S J Appl Physiol 9001; 67(4):1331-5 .M Acetylcholine/*PD; Animal; Bronchi/AH/*PH; Dogs; Muscle Contraction/*DE; Muscle, Smooth/AH/*PH; Myosin/*PH; Support, Non-U.S. Gov't; Trachea/AH/*PH. .T Response to acetylcholine and myosin content of isolated canine airways. .P JOURNAL ARTICLE. .W Contractility of tracheal smooth muscle strips and spiral strips of fourth to fifth generation bronchi was studied in organ baths. The relationship among contractility, airway smooth muscle myosin, and smooth muscle thickness was also examined. The trachea was divided into three segments, each consisting of 12-14 rings. Smooth muscle strips from each of the three regions (top, middle, and bottom of the trachea) and from fourth to fifth generation bronchi were studied. Acetylcholine (ACh) sensitivity (-log EC50) was 8.1, 7.1, 7.9, and 6.1 for the top, middle, and bottom of the trachea and the bronchi, respectively. At P = 0.01, the EC50 ACh value of the top of the trachea differed from the EC50 value of the bronchi. Maximal tension (Tmax) generated in bronchi (3.2 g) was lower (P less than 0.01) than in the top (10.4 g), middle (7.1 g), and bottom of the trachea (5.1 g). Differences between trachea and bronchi disappeared when Tmax was corrected for smooth muscle myosin content. Thickness of smooth muscle in bronchi was less (P less than 0.01) than in the three regions of trachea. Tmax was significantly correlated with airway smooth muscle thickness (r = 0.56; P less than 0.05). These results suggest that in mongrel dogs sensitivity to ACh shows a gradient from the top of the trachea to the bronchi and that Tmax is greater in the trachea than in the bronchi and is significantly correlated with thickness of smooth muscle. .A Mapp CE; Chitano P; De Marzo N; Di Blasi P; Saetta M; Di Stefano A; Bosco VM; Allegra L; Fabbri LM. .I 201296 .U 90008613 .S J Appl Physiol 9001; 67(4):1336-40 .M Altitude Sickness/*CO; Anoxia; Blood Coagulation/*PH; Bradykinin/*BL; Factor XI/ME; Factor XII/ME; Kininogens/BL; Prekallikrein/ME; Prothrombin Time; Pulmonary Edema/*BL/ET; Support, Non-U.S. Gov't. .T Contact phase of blood coagulation is not activated in edema of high altitude. .P JOURNAL ARTICLE. .W To examine whether bradykinin generated by the activation of the contact phase of blood coagulation is involved in the pathogenesis of edema occurring after acute exposure to high altitude, 15 mountaineers were examined at 490 m and 1, 3, and 5 days after arrival at 4,559 m. The clotting activity levels of factor XII, factor XI, plasma prekallikrein, and high-molecular-weight kininogen (HMWK) were measured, and plasma kallikrein-induced proteolytic cleavage of HMWK was assessed by ligand blotting by use of radiolabeled factor XI. After an ascent on foot from 1,170 to 4,559 m in 3 days, three subjects developed high-altitude pulmonary edema, and four subjects presented facial edema. There was no evidence for activation of the contact system in any subject as demonstrated by the lack of proteolytic cleavage of HMWK at high altitude. The absence of contact system activation was further supported by stable plasma levels of the individual factors of contact activation. Therefore, we conclude that bradykinin generated by plasma kallikrein-induced cleavage of HMWK is not involved in the pathogenesis of edema due to acute exposure to high altitude. .A Bartsch P; Lammle B; Huber I; Haeberli A; Vock P; Oelz O; Straub PW. .I 201297 .U 90008615 .S J Appl Physiol 9001; 67(4):1349-53 .M Adolescence; Adult; Aged; Body Height; Body Weight; Female; Human; Lung Volume Measurements; Male; Middle Age; Respiratory Function Tests; Sleep Apnea Syndromes/PA/*PP; Trachea/PA/*PP. .T Tracheal hysteresis in sleep apnea. .P JOURNAL ARTICLE. .W The collapsibility of pharyngeal walls, characteristic of patients with obstructive sleep apnea, likely results from reduced tone of the pharyngeal muscles. This reduction in the upper airway muscle tone may not end at the pharynx but may extend further distally, e.g., into the trachea. Because tracheal tone cannot be measured directly in conscious humans, we inferred the tone from the relative hysteresis of the tracheal area compared with the lung. Relative hysteresis was measured by plotting the cross-sectional area of a tracheal segment obtained by the acoustic reflection technique vs. lung volume. All measurements were performed during wakefulness. We found that in 42 patients with obstructive sleep apnea (apnea/hypopnea index greater than 10), relative hysteresis of the proximal trachea was predominantly clockwise, i.e., smaller than that of the lung parenchyma; in the 33 nonapneic patients (apnea/hypopnea index less than or equal to 10), it was predominantly counter-clockwise, i.e., larger than that of the lung parenchyma. For the distal trachea all patients, apneic and nonapneic, had similar, clockwise, relative hysteresis. We conclude that reduction in the upper airway muscle tone in patients with obstructive sleep apnea extends into the trachea. .A Katz I; Zamel N; Slutsky AS; Rebuck AS; Hoffstein V. .I 201298 .U 90008616 .S J Appl Physiol 9001; 67(4):1354-63 .M Animal; Argon/*AD; Body Weight; Decompression/*; Decompression Sickness/*ET; Diving; Helium/*AD; Kinetics; Male; Oxygen/AD; Pulmonary Gas Exchange/PH; Rats; Rats, Inbred Strains; Risk Factors; Support, U.S. Gov't, Non-P.H.S.. .T Effect of inert gas switching at depth on decompression outcome in rats. .P JOURNAL ARTICLE. .W The present investigation was performed to determine whether inert gas sequencing at depth would affect decompression outcome in rats via the phenomenon of counterdiffusion. Unanesthetized rats (Rattus norvegicus) were subjected to simulated dives in either air, 79% He-21% O2, or 79% Ar-21% O2; depths ranged from 125 to 175 feet of seawater (4.8-6.3 atmospheres absolute). After 1 h at depth, the dive chamber was vented (with depth held constant) over a 5-min period with the same gas as in the chamber (controls) or one of the other two inert gas-O2 mixtures. After the gas switch, a 5- to 35-min period was allowed for gas exchange between the animals and chamber atmosphere before rapid decompression to the surface. Substantial changes in the risk of decompression sickness (DCS) were observed after the gas switch because of differences in potencies (He less than N2 less than Ar) for causing DCS and gas exchange rates (He greater than Ar greater than N2) among the three gases. Based on the predicted gas exchange rates, transient increases or decreases in total inert gas pressure would be expected to occur during these experimental conditions. Because of differences in gas potencies, DCS risk may not directly follow the changes in total inert gas pressure. In fact, a decline in predicted DCS risk may occur even as total inert gas pressure in increasing. .A Lillo RS; MacCallum ME. .I 201299 .U 90008617 .S J Appl Physiol 9001; 67(4):1364-70 .M Animal; Cats; Electric Stimulation; Kainic Acid/PD; Microelectrodes; Motor Neurons/PH; Phrenic Nerve/DE/*PH; Reflex/PH; Respiration/PH; Support, U.S. Gov't, P.H.S.. .T Botzinger complex region role in phrenic-to-phrenic inhibitory reflex of cat. .P JOURNAL ARTICLE. .W Neuronal recordings, microstimulation, and electrolytic and chemical lesions were used to examine the involvement of the Botzinger Complex (BotC) in the bilateral phrenic-to-phrenic inhibitory reflex. Experiments were conducted in decerebrate cats that were paralyzed, ventilated, thoracotomized, and vagotomized. Microelectrode recordings within the BotC region revealed that some neurons were activated by phrenic nerve stimulation (15 of 69 expiratory units, 9 of 67 inspiratory units, and 19 nonrespiratory-modulated units) at average latencies similar to the onset latency of the phrenic-to-phrenic inhibition. In addition, microstimulation within the BotC caused a short latency transient inhibition of phrenic motor activity. In 17 cats phrenic neurogram responses to threshold and supramaximal (15 mA) stimulation of phrenic nerve afferents were recorded before and after electrolytic BotC lesions. In 15 animals the inhibitory reflex was attenuated by bilateral lesions. Because lesion of either BotC neurons or axons of passage could account for this attenuation, in eight experiments the phrenic-to-phrenic inhibitory responses were recorded before and after bilateral injections of 5 microM kainic acid (30-150 nl) into the BotC. After chemical lesions, the inhibitory response to phrenic nerve stimulation remained; however, neuronal activity typical of the BotC could not be located. These results suggest that axons important in producing the phrenic-to-phrenic reflex pass through the region of the BotC, but that BotC neurons themselves are not necessary for this reflex. .A Speck DF. .I 201300 .U 90008618 .S J Appl Physiol 9001; 67(4):1371-6 .M Animal; Comparative Study; Lung/*AH; Pleura/PH; Posture/*PH; Pressure; Pulmonary Alveoli/AH; Rabbits; Regression Analysis; Support, U.S. Gov't, P.H.S.. .T Regional variations in lung expansion in rabbits: prone vs. supine positions. .P JOURNAL ARTICLE. .W We studied the vertical gradient in lung expansion in rabbits in the prone and supine body positions. Postmortem, we used videomicroscopy to measure the size of surface alveoli through transparent parietal pleural windows at dependent and nondependent sites separated in height by 2-3 cm at functional residual capacity (FRC). We compared the alveolar size measured in situ with that measured in the isolated lungs at different deflationary transpulmonary pressures to obtain transpulmonary pressure (pleural surface pressure) in situ. The vertical gradient in transpulmonary pressure averaged 0.48 +/- 0.16 (SD) cmH2O/cm height (n = 10) in the supine position and 0.022 +/- 0.014 (SD) cmH2O/cm (n = 5) in the prone position. In mechanically ventilated rabbits, we used the rib capsule technique to measure pleural liquid pressure at different heights of the chest in prone and supine positions. At FRC, the vertical gradient in pleural liquid pressure averaged 0.63 cmH2O/cm in the supine position and 0.091 cmH2O/cm in the prone position. The vertical gradients in pleural liquid pressure were all less than the hydrostatic value (1 cmH2O/cm), which indicates that pleural liquid is not generally in hydrostatic equilibrium. Both pleural surface pressure and pleural liquid pressure measurements show a greater vertical gradient in the supine than in the prone position. This suggests a close relationship between pleural surface pressure and pleural liquid pressure. Previous results in the dog and pony showed relatively high vertical gradients in the supine position and relatively small gradients in the prone position. This behavior is similar to the present results in rabbits. Thus the vertical gradient is independent of animal size and might be related to chest shape and weight of heart and abdominal contents. .A Yang QH; Kaplowitz MR; Lai-Fook SJ. .I 201301 .U 90008619 .S J Appl Physiol 9001; 67(4):1377-82 .M Adrenal Cortex Hormones/*PD; Airway Resistance/DE; Animal; Animals, Newborn/*PH; Betamethasone/PD; Female; Gestational Age/*; Lung/DE/*EM/PH; Lung Compliance/DE; Pregnancy; Pulmonary Surfactants/PD/*PH; Rabbits; Respiratory Mechanics/DE; Support, U.S. Gov't, P.H.S.. .T Antenatal steroids, postnatal surfactant, and pulmonary function in premature rabbits. .P JOURNAL ARTICLE. .W Antenatal corticosteroids reduce the incidence of the respiratory distress syndrome and improve pulmonary mechanics at least in part by mechanisms other than surfactant stimulation. We measured several aspects of pulmonary function in rabbits to better understand the mechanisms involved. Seven does were given intramuscular betamethasone and six were given vehicle on days 25 and 26 of gestation. Delivery was on day 27 (term = 31). Half of the fetuses from each litter were given rabbit surfactant before the first breath. All fetuses were then ventilated at a consistent tidal volume for 1 h. Pulmonary function tests included static and dynamic compliance, expiratory time constant, stress relaxation, total lung resistance, and total lung conductance. Steroid or surfactant treatment increased dynamic compliance, and the effects of both together were greater than either alone. Static compliance was affected more by surfactant than steroids, whereas lung resistance and conductance were affected more by steroids. The differences in action of the two therapies help account for the increased dynamic compliance seen with combination therapy. .A Gladstone IM; Mercurio MR; Devenny SG; Jacobs HC. .I 201302 .U 90008620 .S J Appl Physiol 9001; 67(4):1383-7 .M Animal; Carbon Monoxide/*PD; Carotid Body/CY/*DE; Endothelium, Vascular/CY; Erythropoiesis/*DE; Hematocrit; Male; Microscopy, Electron; Rats; Rats, Inbred Strains; Support, U.S. Gov't, P.H.S.. .T Chronic CO exposure stimulates erythropoiesis but not glomus cell growth. .P JOURNAL ARTICLE. .W The effect of chronic CO exposure, which stimulates erythropoietin production and erythropoiesis, was studied on carotid body cells in the rat. The hypothesis to be tested was that chronic CO inhalation would stimulate cellular hypertrophy and hyperplasia of carotid body if it caused local tissue hypoxia as in chronic hypoxia. The failure of an appropriate response would indicate a lack of a specific local effect on carotid body tissue PO2 presumably because of its unusually high tissue blood flow. Six young male rats were exposed to 0.4-0.5 Torr (0.05-0.07%) inspired PCO in air for 22 days. Control rats (n = 6) were maintained under similar conditions except for CO exposure. After the exposure period the rats were anesthetized, blood was collected for hematocrit, and the carotid bodies were surgically exposed and fixed for electron microscopy and morphometry of type I and type II cells and capillary endothelium. Hematocrit was significantly greater in the CO-exposed group (75 vs. 48%), whereas no significant difference was found in the carotid body parenchyma between the control and CO-exposed groups. We conclude that the lack of an effect of chronic CO exposure on the carotid bodies in contrast to the strong erythropoietic response indicates a relatively high tissue blood flow rate in the carotid body and that CO did not exert a direct cellular effect. The results also suggest that the hypertrophic response of carotid body glomus cells to chronic hypoxic hypoxia is the result of a local direct effect of low PO2 rather than secondary to systemic effects. .A Sherpa AK; Albertine KH; Penney DG; Thompkins B; Lahiri S. .I 201303 .U 90008621 .S J Appl Physiol 9001; 67(4):1388-94 .M Acetylcholine/AD/*PD; Animal; Atropine/PD; Blood Pressure/DE; Dose-Response Relationship, Drug; Female; Gallamine Triethiodide/PD; Indomethacin/PD; Lung/*BS; Male; Meclofenamic Acid/PD; Pirenzepine/PD; Rabbits; Receptors, Muscarinic/PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Vascular Resistance/*PH; Vasodilation/DE/PH. .T Influence of tone on responses to acetylcholine in the rabbit pulmonary vascular bed. .P JOURNAL ARTICLE. .W Pulmonary vascular responses to acetylcholine were compared under resting and high tone conditions of the intact-chest rabbit. Under resting tone conditions, intralobar injections of acetylcholine increased lobar arterial pressure in a dose-related manner. The pressor responses to acetylcholine under resting conditions were blocked by meclofenamate, indomethacin, atropine, and pirenzepine. When lobar vascular resistance was raised to a high steady level, low doses of acetylcholine decreased lobar arterial pressure, whereas higher doses elicited a biphasic response with the pressor component predominating at the highest dose studied. Under high tone conditions, only the pressor component of the response was blocked by meclofenamate or indomethacin, whereas pressor and depressor responses were blocked by atropine or the 600-micrograms/kg iv dose of pirenzepine. Pressor responses to acetylcholine under resting and high tone conditions were blocked by pirenzepine (50 micrograms/kg iv), whereas gallamine had no effect on responses to acetylcholine. The 50-micrograms/kg iv dose of pirenzepine had no effect on depressor responses or the depressor component of the response to acetylcholine. The present data support the concept that acetylcholine has significant cyclooxygenase-dependent pressor activity in the rabbit pulmonary vascular bed and suggest that this response is mediated by a muscarinic M1-type receptor. These data also show that, under high tone conditions, a vasodilator response or a vasodilator component of a biphasic response is unmasked. This response is not dependent on the release of cyclooxygenase products and is mediated by a muscarinic receptor that is neither of the M1- nor the M2-type. .A Hyman AL; Kadowitz PJ. .I 201304 .U 90008622 .S J Appl Physiol 9001; 67(4):1395-400 .M Animal; Dogs; Electric Stimulation; Intercostal Muscles/*PH; Muscle Contraction/*PH; Pressure; Respiration/*PH; Respiratory Mechanics/PH; Spinal Cord/PH; Support, U.S. Gov't, P.H.S.. .T Inspiratory action of separate external and parasternal intercostal muscle contraction. .P JOURNAL ARTICLE. .W We have previously shown that electrical stimulation of the thoracic spinal cord produces near maximal activation of the inspiratory intercostal muscles. In the present investigation, we used this technique to evaluate the relative capacity of separate external (EI) and parasternal intercostal (PA) muscle contraction to produce changes in airway pressure and inspired volume. Studies were performed in 23 anesthetized phrenicotomized dogs. Electrical stimuli were applied to the spinal cord after hyperventilation-induced apnea, before and after sequentially severing either the PA or EI muscles from the first through sixth intercostal spaces. During spinal cord stimulation (SCS), measurements were made of inspired volume (delta V) with the airway open and negative airway pressure (delta P) during tracheal occlusion. Compared with control values, sectioning of the PA muscles resulted in a 40.9% reduction in delta P and 35.7% reduction in delta V during SCS. In other animals, initial sectioning of the EI muscles produced reductions in delta P and delta V of 67.4 and 63.0, respectively, during SCS. After subsequent section of the PA muscles, SCS produced only negligible inspired volumes and changes in airway pressure. We conclude that 1) the EI and PA muscles are each capable of generating substantial changes in airway pressure and large inspired volumes and 2) the ventilatory capacity of the EI muscles exceeds that of the PA muscles. .A Budzinska K; Supinski G; DiMarco AF. .I 201305 .U 90008623 .S J Appl Physiol 9001; 67(4):1401-8 .M Adenosine Triphosphatase, Myosin/ME; Aging/*PH; Animal; Body Weight; Heart/AH; Male; Muscle Contraction/*PH; Muscles/AH/*PH; Organ Weight; Physical Conditioning, Animal/*; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't; Swimming; Weight Lifting. .T Contractile properties of old rat muscles: effect of increased use. .P JOURNAL ARTICLE. .W To examine how different kinds of activity affect the composition and contractile properties of aging skeletal muscle, old male rats were strength and swim trained. The mass of weights lifted during the strength training increased by 85 +/- 9% (P less than 0.05), which was accompanied by an increase by 32 +/- 5% (P less than 0.05) of the estimated force developed. The wet muscle weight of the soleus and the plantaris decreased significantly with age. The phenomenon was counteracted but not neutralized by the strength training. Twitch and tetanic tension also decreased significantly with age in both the soleus and plantaris muscle. This was avoided by the strength training. This training also significantly decreased time to peak tension and half-relaxation time of both muscles. The swim training increased the heart-to-body weight ratio by 21 +/- 5% (P less than 0.05) and the endurance of the soleus muscle. Time to peak tension and triosephosphate dehydrogenase activity of the plantaris muscle were strongly correlated (P less than 0.001) with myosin adenosinetriphosphatase activity. The results show that the composition and contractile properties of old skeletal muscle are considerably affected by strength training repeated during a substantial period of old age, whereas swim training only affects the endurance of the skeletal muscle. .A Klitgaard H; Marc R; Brunet A; Vandewalle H; Monod H. .I 201306 .U 90008624 .S J Appl Physiol 9001; 67(4):1409-17 .M Adenosine Triphosphate/ME; Aging/*PH; Animal; Citrate Synthase/ME; Glyceraldehydephosphate Dehydrogenase/ME; Glycogen/ME; Hexokinase/ME; Lactate Dehydrogenase/ME; Lactate Dehydrogenase Isoenzymes/ME; Male; Muscles/*AH/EN; Phosphocreatine/ME; Physical Conditioning, Animal/*; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't; Swimming; Weight Lifting. .T Morphological and biochemical changes in old rat muscles: effect of increased use. .P JOURNAL ARTICLE. .W Male Wistar rats were strength and swim trained during a substantial period of old age to determine the influence of aging and activity on the histochemical and metabolic characteristics of a predominantly slow (soleus) and a predominantly fast (plantaris) skeletal muscle. Strength training counteracted the age-related atrophy of the fibers and the age-induced changes in fiber-type distribution of both muscles. Swim training, on the other hand, was without any effect on these parameters. The activity of both mitochondrial and cytoplasmic enzymes became lower with aging in the soleus muscle, whereas only the activity of the cytoplasmic enzymes became lower in the plantaris. Strength training reduced the aerobic capacity of both muscles, whereas swim training had the opposite effect. Aging induced a lower glycogen concentration of the lateral gastrocnemius muscle. This was avoided by swim training. The phosphocreatine and adenosine 5'-triphosphate concentrations were unchanged with aging but became higher with strength training. The activity pattern, therefore, seems to have a considerable influence on the age-related modification of the histochemical and metabolic characteristics of skeletal muscles of the rat. The effect, however, is related to the recruitment pattern of the fiber populations and the form of activity. .A Klitgaard H; Brunet A; Maton B; Lamaziere C; Lesty C; Monod H. .I 201307 .U 90008625 .S J Appl Physiol 9001; 67(4):1418-21 .M Animal; Biomechanics; Carnivora/*PH; Ferrets/*PH; Lung/*GD; Male; Pneumonectomy/*; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Total Lung Capacity. .T Lung volumes after an increase in lung distension in pneumonectomized ferrets. .P JOURNAL ARTICLE. .W To investigate the role of lung distension in compensatory lung growth, the right lung of each of 21 adult male ferrets was replaced with a silicone rubber balloon filled with mineral oil. Three to thirteen weeks after surgery, the oil was removed through a subcutaneous port. Lung volumes were measured serially until 3-6 wk after balloon deflation. With pneumonectomy the total lung capacity (TLC) decreased to less than 50% of the preoperative value and remained essentially unchanged while the balloon was inflated. At balloon deflation, TLC and vital capacity did not change immediately, whereas functional residual capacity increased by 44%, indicating a change of 2-3 cmH2O in end-expiratory transpulmonary pressure. TLC increased by 10% within 3 days and continued to increase over the subsequent 3-5 wk by a total of 25% over TLC at balloon deflation. There was little difference in this response between animals whose balloons were deflated 3 wk after surgery and those in which deflation was delayed up to 13 wk. After pneumonectomy in the adult ferret, the remaining lung increases in volume in response to an increase in lung distension even weeks or months after surgery. The extent to which this volume increase involves lung tissue growth or depends on previous lung resection is at present unknown. This model may be useful for studies of the mechanisms by which lung distension influences lung volume and compensatory lung growth. .A McBride JT. .I 201308 .U 90008626 .S J Appl Physiol 9001; 67(4):1422-7 .M Animal; Animals, Newborn/*GD; Biomechanics; Elasticity; Female; Lung/*GD/PH; Mathematics; Membranes/PH; Pleura/PH; Support, U.S. Gov't, P.H.S.; Swine. .T Elastic moduli of lungs during postnatal development in the piglet. .P JOURNAL ARTICLE. .W Several manifestations of lung disease during infancy suggest that mechanical interdependence can be relatively high in newborn lungs. To test this possibility, we measured elastic moduli and pleural membrane tension in lungs excised from piglets ranging in age from less than 12 h to 85 days. Near maximum inflation, newborn lungs (less than 12 h, n = 6) had no detectable pleural membrane tension, although 3- to 5-day-old lungs (n = 6) had tension greater than 5,000 dyn/cm. In contrast, parenchymal recoil was greater in the newborn lungs [19.3 +/- 3.0 (SD) vs. 14.3 +/- 2.4 cmH2O at 90% of maximum inflation volume, P less than 0.01]. Shear moduli were higher (13.5 +/- 4.6 vs. 9.2 +/- 1.5 cmH2O at 15 cmH2O transpulmonary pressure, P less than 0.05) and Poisson ratios were lower in the newborn lungs as compared with the 3- to 5-day-old lungs. Postnatal lung growth between 3 and 85 days was characterized by 1) a constant shear modulus (0.6 times transpulmonary pressure); 2) decrease in the bulk modulus (from 6.8 to 5.1 times transpulmonary pressure, P less than 0.005); and 3) evidence of gas trapping at progressively higher transpulmonary pressures. Therefore, growth of parenchyma in the piglet lung is associated with reduced stiffness to volume change but with no effect on overall stiffness to shape change. Nevertheless, a relatively great stiffness to shape change occurs transiently in newborn piglet lungs. .A Mansell AL; Moalli RR; Calista CL; Pipkin AC. .I 201309 .U 90008627 .S J Appl Physiol 9001; 67(4):1428-37 .M Administration, Inhalation; Animal; Blood Pressure/DE; Bronchi/DE/PH; Capsaicin/AD/*PD; Chemoreceptors/DE/PH; Comparative Study; Dogs; Female; Heart Rate/DE; Injections, Intravenous; Larynx/PH; Lung/IR/*PH; Male; Rats; Rats, Inbred Strains; Reflex/DE/*PH; Respiration/PH; Support, U.S. Gov't, P.H.S.; Trachea/DE/PH; Vagotomy; Vagus Nerve/PH. .T Reflex responses to capsaicin: intravenous, aerosol, and intratracheal administration [published errata appear in J Appl Physiol 1990 Jan;68(1):following Table of Contents and 1990 Jun;68(6):following 2701] .P JOURNAL ARTICLE. .W Intravenous capsaicin elicits the "pulmonary chemoreflex" (apnea, bradycardia, and hypotension) presumably through the stimulation of "pulmonary C-fibers." The present study was designed to ascertain whether tracheobronchial C-fibers play a role in the above reflex response. We compared the effects of capsaicin injected intravenously, administered as an aerosol, and administered topically into the intrathoracic trachea in anesthetized dogs (n = 17) and rats (n = 17). We measured esophageal, subglottic, and arterial pressures together with abdominal muscle electromyogram. Changes in expiratory duration [(TE), measured as the ratio TEtest to TEcontrol, mean +/- SD] due to capsaicin were similar with all three routes of administration in both dogs (intravenous, 7.9 +/- 4.6; aerosol, 5.5 +/- 3.1; topically into intrathoracic trachea, 7.1 +/- 4.8) and rats (intravenous, 22.6 +/- 10.3; aerosol, 11.1 +/- 8.2; topically into intrathoracic trachea, 21.6 +/- 4.6). An increase in laryngeal resistance was a constant finding in the rat, but it was less frequent in the dog. Cardiovascular responses consisting of bradycardia and hypotension occurred with all three routes of administration but had longer delays than the respiratory responses. Capsaicin instillation into the extrathoracic trachea in dogs (n = 7) also induced qualitatively similar cardiorespiratory responses. We conclude that 1) capsaicin-sensitive receptors are accessible from both the pulmonary circulation and the airway lumen and 2) afferents, even in the extrapulmonary portion of the tracheobronchial tree, can play a role in the reflex responses to intraluminal capsaicin. .A Palecek F; Sant'Ambrogio G; Sant'Ambrogio FB; Mathew OP. .I 201310 .U 90008628 .S J Appl Physiol 9001; 67(4):1438-42 .M Animal; Dogs; Electromyography; Lung Volume Measurements; Muscle Denervation; Posture/*PH; Respiration/PH; Respiratory Muscles/*PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tidal Volume/*PH. .T Expiratory muscle contribution to tidal volume in head-up dogs. .P JOURNAL ARTICLE. .W A change from the supine to the head-up posture in anesthetized dogs elicits increased phasic expiratory activation of the rib cage and abdominal expiratory muscles. However, when this postural change is produced over a 4- to 5-s period, there is an initial apnea during which all the muscles are silent. In the present studies, we have taken advantage of this initial silence to determine functional residual capacity (FRC) and measure the subsequent change in end-expiratory lung volume. Eight animals were studied, and in all of them end-expiratory lung volume in the head-up posture decreased relative to FRC [329 +/- 70 (SE) ml]. Because this decrease also represents the increase in lung volume as a result of expiratory muscle relaxation at the end of the expiratory pause, it can be used to determine the expiratory muscle contribution to tidal volume (VT). The average contribution was 62 +/- 6% VT. After denervation of the rib cage expiratory muscles, the reduction in end-expiratory lung volume still amounted to 273 +/- 84 ml (49 +/- 10% VT). Thus, in head-up dogs, about two-thirds of VT result from the action of the expiratory muscles, and most of it (83%) is due to the action of the abdominal rather than the rib cage expiratory muscles. .A Farkas GA; Estenne M; De Troyer A. .I 201311 .U 90008629 .S J Appl Physiol 9001; 67(4):1443-6 .M Arthritis, Rheumatoid/PA; Bronchoalveolar Lavage Fluid/*PA; Cell Count; Eosinophils/PA; Female; Human; Irrigation/MT; Lymphocytes/PA; Macrophages/PA; Male; Neutrophils/PA; Pulmonary Fibrosis/*PA; Sarcoidosis/PA; Support, U.S. Gov't, P.H.S.. .T Bronchoalveolar lavage in interstitial lung disease: effect of volume of fluid infused. .P JOURNAL ARTICLE. .W To evaluate the effect of varying infusate volume on the results of bronchoalveolar lavage (BAL) in patients with interstitial lung disease, 55 patients underwent 58 BAL during which both a 100- and 250-ml lavage was performed in the same lobe of the lung. Although the percent of the fluid that was returned and the total numbers of cells were greater in the 250- vs. the 100-ml lavage, there were no significant differences in cell differentials or numbers of cells per milliliter between the 100- and 250-ml BAL. We conclude that infusate volume does not affect cell differentials or numbers of cells per milliliter of bronchoalveolar lavage fluid in patients with interstitial lung disease. .A Helmers RA; Dayton CS; Floerchinger C; Hunninghake GW. .I 201312 .U 90008630 .S J Appl Physiol 9001; 67(4):1447-55 .M Adult; Arrhythmia, Sinus/*; Denervation/*; Electrocardiography; Female; Heart/*IR; Heart Rate/*PH; Heart Transplantation/*; Human; Male; Middle Age; Respiration/*PH; Support, U.S. Gov't, Non-P.H.S.; Valsalva's Maneuver. .T Respiratory sinus arrhythmia in the denervated human heart. .P JOURNAL ARTICLE. .W We performed this study to test whether the denervated human heart has the ability to manifest respiratory sinus arrhythmia (RSA). With the use of a highly sensitive spectral analysis technique (cross correlation) to define beat-to-beat coupling between respiratory frequency and heart rate period (R-R) and hence RSA, we compared the effects of patterned breathing at defined respiratory frequency and tidal volumes (VT), Valsalva and Mueller maneuvers, single deep breaths, and unpatterned spontaneous breathing on RSA in 12 normal volunteers and 8 cardiac allograft transplant recipients. In normal subjects R-R changes closely followed changes in respiratory frequency (P less than 0.001) but were little affected by changes in VT. On the R-R spectrum, an oscillation peak synchronous with respiration was found in heart transplant patients. However, the average magnitude of the respiration-related oscillations was 1.7-7.9% that seen in normal subjects and was proportionally more influenced by changes in VT. Changes in R-R induced by Valsalva and Mueller maneuvers were 3.8 and 4.9% of those seen in normal subjects, respectively, whereas changes in R-R induced by single deep breaths were 14.3% of those seen in normal subjects. The magnitude of RSA was not related to time since the heart transplantation, neither was it related to patient age or sex. Thus the heart has the intrinsic ability to vary heart rate in synchrony with ventilation, consistent with the hypothesis that changes, or rate of changes, in myocardial wall stretch might alter intrinsic heart rate independent of autonomic tone. .A Bernardi L; Keller F; Sanders M; Reddy PS; Griffith B; Meno F; Pinsky MR. .I 201313 .U 90008631 .S J Appl Physiol 9001; 67(4):1456-62 .M Acclimatization/*PH; Adult; Altitude/*; Anoxia/ME; Exercise/*PH; Femoral Artery; Human; Iliac Vein; Lactates/*BL; Male; Muscles/*ME; Oxygen Consumption/PH; Support, U.S. Gov't, P.H.S.. .T Decreased exercise muscle lactate release after high altitude acclimatization. .P JOURNAL ARTICLE. .W Blood lactate concentration during exercise decreases after acclimatization to high altitude, but it is not clear whether there is decreased lactate release from the exercising muscle or if other mechanisms are involved. We measured iliac venous and femoral arterial lactate concentrations and iliac venous blood flow during cycle exercise before and after acclimatization to 4,300 m. During hypoxia, at a given O2 consumption the venous and arterial lactate concentrations, the venous and arterial concentration differences, and the net lactate release were lower after acclimatization than during acute altitude exposure. While breathing O2-enriched air after acclimatization at a given O2 consumption the venous and arterial lactate concentrations and the venous and arterial concentration differences were significantly lower, and the net lactate release tended to be lower than while breathing ambient air at sea level before acclimatization. We conclude that the lower lactate concentration in venous and arterial blood during exercise after altitude acclimatization reflected less net release of lactate by the exercising muscles, and that this likely resulted from the acclimatization process itself rather than the hypoxia per se. .A Bender PR; Groves BM; McCullough RE; McCullough RG; Trad L; Young AJ; Cymerman A; Reeves JT. .I 201314 .U 90008632 .S J Appl Physiol 9001; 67(4):1463-71 .M Animal; Blood Pressure; Complement Inactivators/*TU; Complement 3a/ME; Drug Interactions; Guanidines/*TU; Hemodynamics/PH; Heparin/AD/*AE/TU; Hypertension, Pulmonary/CI/*PC; Lung/BS; Protamines/AD/*AE/TU; Protease Inhibitors/*TU; Pulmonary Artery/PP; Sheep; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Thromboxane B2/BL; Vascular Resistance. .T Nafamstat mesilate attenuates pulmonary hypertension in heparin-protamine reactions. .P JOURNAL ARTICLE. .W Rapid protamine reversal of heparin anticoagulation in awake sheep caused, after 1 min, a approximately 15-fold increase of arterial plasma thromboxane B2 (TxB2) levels, a 4-fold rise of pulmonary vascular resistance (PVR), a 2-fold rise of pulmonary arterial pressure, and after 3 min, a 2-fold rise of ovine arterial plasma complement C3a levels (P less than 0.05). Infusion of nafamstat mesilate (FUT-175), a protease and complement pathway inhibitor, before protamine reduced these increases by approximately 60-90% (P less than 0.05). FUT-175 did not modify heparin + protamine-induced leukopenia, suggesting that FUT-175 incompletely blocked C5a production. We also learned that infusing protamine first and heparin 5 min later did not increase either plasma C3a or TxB2 levels or PVR while the activated clotting time increased only minimally. Thus, in awake sheep, the sequence of heparin and protamine infusion influences complement activation and pulmonary vasoconstriction. FUT-175 pretreatment reduces thromboxane release and pulmonary vasoconstriction probably by limiting complement activation. .A Kreil E; Montalescot G; Greene E; Fitzgibbon C; Robinson D; Chenoweth D; Zapol WM. .I 201315 .U 90008633 .S J Appl Physiol 9001; 67(4):1472-8 .M Abdomen/*PH; Animal; Biomechanics; Dogs; Lung/*PH; Lung Volume Measurements; Plethysmography, Whole Body; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Thorax/*PH; Tidal Volume/PH; Tracheostomy. .T Rib cage vs. abdominal displacement in dogs during forced oscillation to 32 Hz. .P JOURNAL ARTICLE. .W Allen et al. (J. Clin. Invest. 76: 620-629, 1985) reported that during oscillatory forcing the base of isolated canine lungs distends preferentially relative to the apex as frequency and tidal volume increase. The tendency toward such nonuniform phasic lung distension might influence phasic displacement of the rib cage (RC) relative to the abdomen (ABD). To test this hypothesis we measured RC and ABD displacement in four anesthetized dogs during forced oscillation. Sinusoidal volume changes were delivered through a tracheostomy at 1-32 Hz and measured by body plethysmography. RC and ABD displacements were measured by inductive plethysmography. During oscillation with air at fixed tidal volumes (10-80 ml) RC, normalized to unity at 1 Hz, increased to 2.06-2.22 at 8 Hz (P less than 0.001) and then decreased to 1.06-1.35 (P less than 0.0025) at 32 Hz. ABD, normalized to unity at 1 Hz, was 1.12-1.16 at 4 Hz (P less than 0.001) and decreased to 0.12-0.14 at 32 Hz (P less than 0.001). Displacement of ABD relative to RC did not increase systematically with increasing tidal volume during sinusoidal forcing at any frequency. Thus we found no discernible influence of nonuniform phasic lung distension on chest wall behavior. We infer that in the dog the nonuniform mechanical behavior of the chest wall dominates the nonuniform (but opposing) mechanical tendency of the lung. .A Boynton BR; Glass G; Frantz ID 3d; Fredberg JJ. .I 201316 .U 90008634 .S J Appl Physiol 9001; 67(4):1479-88 .M Acetylcholine/PD; Animal; Blood Platelets/*PA; Blood Volume; Erythrocytes/*PA; Extracellular Space/*ME; Guinea Pigs; Indium Radioisotopes; Iodine Radioisotopes; Lung/BS/ME/PA; N-Formylmethionine Leucyl-Phenylalanine/PD; Neutrophils/*PA; Platelet Activating Factor/PD; Pneumonia/ME/*PA; Serum Albumin/*ME; Technetium; Tidal Volume. .T A new method to evaluate extravascular albumin and blood cell accumulation in the lung. .P JOURNAL ARTICLE. .W A method was developed to evaluate blood volume, accumulation of extravascular albumin (ALBev), and platelet (PL) or polymorphonuclear neutrophil (PMN) sequestration in lungs after challenge with inflammatory agents. Erythrocytes (RBC), albumin, and PL or PMN, labeled with 99mTc, 131I, and 111In,-respectively, were injected intravenously into anesthetized and ventilated guinea pigs. The different parameters were calculated from in vivo lung and blood radioactivity values. When N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) was injected intravenously at 10 micrograms.kg-1, lung RBC content dropped by 14.7 +/- 1.8% (SE; n = 10), indicating a reduced lung blood volume, ALBev rose to 15.0 +/- 3.2% of the initial albumin vascular content, and the circulating PMN were sequestered by 9.2 +/- 1.7%. A transient PL sequestration was also observed 1 min after the injection of fMLP (13.1 +/- 2.0%, n = 7). During the infusion of 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphorylcholine, the lung PL content rose dose dependently from 10.1 +/- 2.2% of the circulating pool with 3 ng.kg-1.min-1 to 54.9 +/- 20.1% with 44 ng.kg-1.min-1, the lung RBC content decreased by greater than 10%, and the ALBev increased beyond 16%. Our method allows the study of the correlations between cell entrapment and the variations of the albumin exchanges in the lung and may lead to a better understanding of the correlations between cell activation and edema. .A Bureau MF; Malanchere E; Pretolani M; Boukili MA; Vargaftig BB. .I 201317 .U 90008635 .S J Appl Physiol 9001; 67(4):1489-94 .M Animal; Dogs; Lung/PA; Mucous Membrane/PA; Necrosis; Oxygen/AD/BL; Pressure; Pulmonary Alveoli/*PH; Pulmonary Gas Exchange/*PH; Respiration, Artificial/*/AE; Respiratory Mechanics/PH; Support, U.S. Gov't, P.H.S.. .T Alveolar pressure inhomogeneity and gas exchange during constant-flow ventilation in dogs. .P JOURNAL ARTICLE. .W Analysis of momentum transfer between inflow jets and resident gas during constant-flow ventilation (CFV) predicts inhomogeneity of alveolar pressures (PA) and volume, which might account for specific ventilation-variance in the lung. Using alveolar needles to measure pressures (PA) during CFV in eight anesthetized dogs with wide thoracotomy, we observed random dispersion of PA among lobes of up to 12.5 cmH2O. Within each lobe, the PA dispersion was up to 10 cmH2O at CFV of 90 l/min; when flow decreased, PA at all sites decreased, as did the intralobar dispersion. These pressure differences were not observed during conventional mechanical ventilation (CMV). During CFV with room air, dogs were hypoxemic [arterial PO2 (Pao2) 54 +/- 15 Torr] and the venous admixture (Qva/QT) was 50 +/- 15%. When inspiratory O2 fraction was increased to 0.4, Pao2 increased to 172 +/- 35 Torr and Qva/QT dropped to 13.5 +/- 8.4%, confirming considerable ventilation-perfusion (VA/Q) variance not observed during CMV. We conclude that momentum transfer between the inflow stream and resident gas caused inhomogeneities of alveolar pressures, volumes, and ventilation responsible for VA/Q variance and hypoxemia during CFV. Conceivably, the abnormal ventilation distribution is minimized by collateral ventilation and forces of interdependence between regions of high and low alveolar pressures. Momentum transfer also predicted the mucosal damage observed on histological evaluation of the bronchial walls near the site of inflow jet impact. .A Sznajder JI; Nahum A; Crawford G; Pollak ER; Schumacker PT; Wood LD. .I 201318 .U 90008637 .S J Appl Physiol 9001; 67(4):1504-11 .M Animal; Bronchi/*DE/PP; Capsaicin/PD; Constriction, Pathologic; Electric Stimulation; Glycopeptides/PD; Guinea Pigs; Male; Membrane Metallo-Endopeptidase/AI/*PH; Muscle, Smooth/PP; Para-Influenza/*PP; Para-Influenza Virus Type 1; Respiratory Tract Infections/ET/*PP; Substance P/PD; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Tachykinins/*PD. .T Virus induces airway hyperresponsiveness to tachykinins: role of neutral endopeptidase. .P JOURNAL ARTICLE. .W We examined the effects of viral respiratory infection by Sendai virus on airway responsiveness to tachykinins in guinea pigs. We measured the change in total pulmonary resistance induced by substance P or capsaicin in the presence or absence of the neutral endopeptidase inhibitor, phosphoramidon, in infected and in noninfected animals. In the absence of phosphoramidon, the bronchoconstrictor responses to substance P and to capsaicin were greater in infected than in noninfected animals. Phosphoramidon did not further potentiate the responses to substance P and to capsaicin in the infected animals, whereas it did so in noninfected animals. Studies performed in vitro showed that nonadrenergic noncholinergic bronchial smooth muscle responses to electrical field stimulation were also increased in tissues from infected animals and that phosphoramidon increased the response of tissues from noninfected animals greatly but increased the responses of tissues from infected animals only slightly. Responses to acetylcholine were unaffected by viral infection. Neutral endopeptidase activity was decreased by 40% in the tracheal epithelial layer of the infected animals. We suggest that respiratory infection by Sendai virus causes enhanced airway responsiveness to tachykinins by decreasing neutral endopeptidase-like activity in the airway epithelium. .A Dusser DJ; Jacoby DB; Djokic TD; Rubinstein I; Borson DB; Nadel JA. .I 201319 .U 90008640 .S J Appl Physiol 9001; 67(4):1525-34 .M Action Potentials; Diaphragm/*PH; Electrodes; Electromyography/*MT; Human; Respiration; Support, U.S. Gov't, P.H.S.; Tidal Volume. .T Diaphragmatic electromyography using a multiple electrode array. .P JOURNAL ARTICLE. .W We have developed a new technique for diaphragmatic electromyography using an array of seven sequential electrode pairs at 1.0-cm spacing on an esophageal catheter. This array provides information about the spatial distribution of the electrical field generated by the diaphragm and reveals a sharply peaked variation of electrical potential with distance along the esophagus. The rectified and integrated information from each of the seven pairs is summed to give an approximation to the total electrical activity over the span of the array, providing a signal that is relatively insensitive to the position of the array over approximately 4 cm of catheter movement and removes the requirement for balloon stabilization of the catheter. With our array, we have confirmed the artifact in the evoked compound muscle action potential that seems to be related to diaphragmatic shape as reported by others who used supramaximal phrenic nerve stimulation, but the magnitude of this artifact (compared with the functional residual capacity level) was modest near functional residual capacity, averaging 12 +/- 14% (SD) for lung volumes 1.0 l above and -4 +/- 15% for lung volumes 1.0 l below functional residual capacity along the rib cage-abdomen relaxation line. .A Daubenspeck JA; Leiter JC; McGovern JF; Knuth SL; Kobylarz EJ. .I 201320 .U 90008641 .S J Appl Physiol 9001; 67(4):1535-41 .M Adult; Airway Resistance/DE; Exercise; Human; Lidocaine/PD; Lung/*DE/PH; Lung Compliance/DE; Male; Ozone/*PD; Respiration/DE; Respiratory Mechanics/DE; Support, U.S. Gov't, Non-P.H.S.; Tidal Volume/DE; Vital Capacity/DE. .T Mechanism of action of ozone on the human lung. .P JOURNAL ARTICLE. .W Fourteen healthy normal volunteers were randomly exposed to air and 0.5 ppm of ozone (O3) in a controlled exposure chamber for a 2-h period during which 15 min of treadmill exercise sufficient to produce a ventilation of approximately 40 l/min was alternated with 15-min rest periods. Before testing an esophageal balloon was inserted, and lung volumes, flow rates, maximal inspiratory (at residual volume and functional residual capacity) and expiratory (at total lung capacity and functional residual capacity) mouth pressures, and pulmonary mechanics (static and dynamic compliance and airway resistance) were measured before and immediately after the exposure period. After the postexposure measurements had been completed, the subjects inhaled an aerosol of 20% lidocaine until response to citric acid aerosol inhalation was abolished. All of the measurements were immediately repeated. We found that the O3 exposure 1) induced a significant mean decrement of 17.8% in vital capacity (this change was the result of a marked fall in inspiratory capacity without significant increase in residual volume), 2) significantly increased mean airway resistance and specific airway resistance but did not change dynamic or static pulmonary compliance or viscous or elastic work, 3) significantly reduced maximal transpulmonary pressure (by 19%) but produced no changes in inspiratory or expiratory maximal mouth pressures, and 4) significantly increased respiratory rate (in 5 subjects by more than 6 breaths/min) and decreased tidal volume.(ABSTRACT TRUNCATED AT 250 WORDS) .A Hazucha MJ; Bates DV; Bromberg PA. .I 201321 .U 90008642 .S J Appl Physiol 9001; 67(4):1542-50 .M Abdomen/PH; Functional Residual Capacity; Human; Inspiratory Capacity; Lung Volume Measurements/*; Respiration/*PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Thorax/*PH; Tidal Volume; Vital Capacity; Weightlessness/*. .T Lung volumes, chest wall configuration, and pattern of breathing in microgravity. .P JOURNAL ARTICLE. .W We studied the changes in functional residual capacity (FRC), thoracoabdominal volume (Vw), and chest wall configuration in five normal subjects seated in an aircraft flying parabolic trajectories resulting in 20-s periods of microgravity. We measured vital capacity (VC), inspiratory capacity, and tidal volume by integrating airflow at the mouth and changes in rib cage and abdominal volume (delta Vrc and delta Vab, respectively, where delta Vrc + delta Vab = delta Vw) using induction plethysmography. During microgravity (0 Gz) FRC decreased by 413 +/- 70 (SE) ml and VC by 0.37 liter. The decrease in Vw did not differ from that in FRC and was entirely the result of reduction of Vab, the Vrc showing no significant change. During tidal breathing the abdominal contribution (delta Vab/delta Vw) increased from 0.39 +/- 0.08 at 1 Gz to 0.57 +/- 0.08 at 0 Gz. During brief periods of hypergravity (approximately 1.8 Gz) all changes were opposite in sign and relatively smaller. Limited data during "roller coaster" flight patterns suggested that, in contrast to configurational changes, the temporal pattern of breathing was uninfluenced by changes in Gz. We conclude that at the onset of weightlessness there are substantial changes in lung volume and thoracoabdominal configuration. Abdominal contribution to tidal excursions increases but the temporal pattern of breathing is unchanged. .A Paiva M; Estenne M; Engel LA. .I 201322 .U 90008643 .S J Appl Physiol 9001; 67(4):1551-9 .M Animal; Cardiac Output/*DE; Dogs; Female; Heart Rate/DE; Lung/BS; Male; Myocardium/ME; Oxygen/*AD/BL/PD; Oxygen Consumption/*DE; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Vascular Resistance/DE. .T Decreased O2 consumption and cardiac output during normobaric hyperoxia in conscious dogs. .P JOURNAL ARTICLE. .W Recent reports indicate that under certain restricted conditions hyperoxia may decrease tissue O2 consumption. However, this effect has not been established for whole body O2 consumption in the intact healthy conscious state. The goal of the present study was to document the effect of hyperoxia on resting whole body O2 consumption and hemodynamics under these latter more general physiological conditions. The inspired gas was delivered by mask to six fasted resting conscious dogs and alternated hourly between air and O2-enriched air (hyperoxia) for 5 h, while hemodynamics and blood gas data were obtained every 20 min. Compared with air breathing, hyperoxia increased the mean arterial O2 tension from 95 to 475 Torr and decreased heart rate, cardiac output, pulmonary vascular resistance, and right and left ventricular work rates and thus, presumably, myocardial O2 consumption. Hyperoxia also increased systemic vascular resistance and right atrial pressure but did not change stroke volume or systemic arterial pressure. The increase in arterial O2 content during hyperoxia was counterbalanced by the decrease in cardiac output, so that O2 delivery was unchanged by hyperoxia. Surprisingly, hyperoxia decreased the arterial-to-mixed venous difference in O2 content; this decrease together with the decrease in cardiac output produced a decrease in resting whole body O2 consumption from 5.88 +/- 0.68 to 4.80 +/- 0.62 ml O2.min-1.kg-1 (P = 0.0002). It is concluded that under physiological conditions normobaric hyperoxia may decrease metabolic rate in addition to cardiac output, which may have important implications for the metabolic regulation of O2 utilization as well as for the medical and nonmedical uses of O2. .A Lodato RF. .I 201323 .U 90008646 .S J Appl Physiol 9001; 67(4):1578-84 .M Animal; Carotid Body/*ME; Cats; Denervation/*; Female; Kinetics; Male; Microelectrodes; Oxygen Consumption/*PH; Support, U.S. Gov't, P.H.S.. .T Evidence for second metabolic pathway for O2 from PtiO2 measurements in denervated cat carotid body. .P JOURNAL ARTICLE. .W O2 microelectrode studies were conducted in the cat carotid body (CB) to investigate the hypothesis that there is a second, low affinity metabolic pathway for O2 in addition to classical oxidative metabolism. Tissue PO2 (PtiO2) and O2 disappearance rates (dPO2/dt) after brief blood flow occlusion were measured with recessed cathode microelectrodes (tip diameter less than 5 microns) at 150 sites in 15 normal cats (controls) and at 154 sites in 5 cats in which one CB had been denervated 2 or 3 days before the experiments. Mean PtiO2 was slightly higher in denervated CBs: 79.6 +/- 1.6 (SE) Torr compared with 76.4 +/- 2.0 Torr for controls (P = not significant). Mean dPO2/dt was 8.4% faster: -8.42 +/- 0.28 Torr/s compared with -7.77 +/- 0.43 Torr/s for controls (P less than 0.05). The O2 consumption rate (VO2), calculated from dPO2/dt correcting for cat oxyhemoglobin, was 7.5% higher: 1.62 and 1.51 ml.100 g-1.min-1, respectively, for denervated and control CBs (P less than 0.05). The apparent Michaelis-Menten constant, Kmapp (defined as the PtiO2 where dPO2/dt decreased by 50% from the initial rate during the first 3 s after occlusion) was determined for each O2 disappearance curve. After denervation, Kmapp decreased significantly by -47%: 12.0 +/- 1.3 Torr compared with 22.6 +/- 2.5 Torr for controls (P less than 0.01). The data provide evidence for a second metabolic pathway for O2 in the CB that loses its influence on VO2 after denervation. .A Buerk DG; Nair PK; Whalen WJ. .I 201324 .U 90008647 .S J Appl Physiol 9001; 67(4):1585-90 .M Animal; Cattle; Cell Cycle/RE; Cell Division/RE; Cell Survival/RE; Endothelium, Vascular/*CY/RE; Flow Cytometry; Interphase/RE; Male; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Endothelial cell subpopulations in vitro: cell volume, cell cycle, and radiosensitivity. .P JOURNAL ARTICLE. .W Vascular endothelial cells (EC) are important clinical targets of radiation and other forms of free radical/oxidant stresses. In this study, we found that the extent of endothelial damage may be determined by the different cytotoxic responses of EC subpopulations. The following characteristics of EC subpopulations were examined: 1) cell volume; 2) cell cycle position; and 3) cytotoxic indexes for both acute cell survival and proliferative capacity after irradiation (137Cs, gamma, 0-10 Gy). EC cultured from bovine aortas were separated by centrifugal elutriation into subpopulations of different cell volumes. Through flow cytometry, we found that cell volume was related to the cell cycle phase distribution. The smallest EC were distributed in G1 phase and the larger cells were distributed in either early S, middle S, or late S + G2M phases. Cell cycle phase at the time of irradiation was not associated with acute cell loss. However, distribution in the cell cycle did relate to cell survival based on proliferative capacity (P less than 0.01). The order of increasing radioresistance was cells in G1 (D0 = 110 cGy), early S (135 cGy), middle S (145 cGy), and late S + G2M phases (180 cGy). These findings 1) suggest an age-related response to radiation in a nonmalignant differentiated cell type and 2) demonstrate EC subpopulations in culture. .A Rubin DB; Drab EA; Bauer KD. .I 201325 .U 90008648 .S J Appl Physiol 9001; 67(4):1591-6 .M Airway Resistance/PH; Animal; Bronchial Fistula/*PP; Fistula/*PP; Lung/PP; Pleural Diseases/*PP; Pressure; Rabbits; Respiratory Mechanics/*PH; Thorax/PP. .T Determinants of gas flow through a bronchopleural fistula. .P JOURNAL ARTICLE. .W To assess the determinants of bronchopleural fistula (BPF) flow, we used a surgically created BPF to study 15 anesthetized intubated mechanically ventilated New Zealand White rabbits. Mean airway pressure and intrathoracic pressure were evaluated independently. Mean airway pressure was varied (8, 10, or 12 cmH2O) by independent manipulations of either peak inspiratory pressure, positive end-expiratory pressure, or inspiratory time. Intrathoracic pressure was varied from 0 to -40 cmH2O. BPF flow varied directly with mean airway pressure (P less than 0.001). However, at constant mean airway pressure, BPF flow was not influenced independently by changes in peak inspiratory pressure, positive end-expiratory pressure, or inspiratory time. Resistance of the BPF increased as intrathoracic pressure became more negative. Despite increased resistance, BPF flow also increased. BPF resistance was constant over the range of mean airway (P less than 0.01) pressures investigated. Our data document the influence of mean airway pressure and intrathoracic pressure on BPF flow and suggest that manipulations which reduce transpulmonary pressure will decrease BPF flow. .A Walsh MC; Carlo WA. .I 201326 .U 90008649 .S J Appl Physiol 9001; 67(4):1597-605 .M Animal; Animals, Newborn/*ME; Bronchoalveolar Lavage Fluid/ME; Choline/ME; Kinetics; Lactate Dehydrogenase/ME; Lung/EM/*ME; Metabolic Clearance Rate; Phospholipids/ME; Pulmonary Alveoli/ME; Pulmonary Surfactants/*ME; Rabbits; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tritium. .T Surfactant secretion and clearance in the newborn. .P JOURNAL ARTICLE. .W Pregnant rabbits (30 days) were injected intravenously with [3H]choline 8 h before delivery. The fetuses were delivered, and lung lavage and lamellar body phospholipids (PL) were analyzed. Some newborns also received radioactively labeled surfactant intratracheally on delivery and were permitted to breathe. With time, intratracheal label decreased in lavage and appeared in the lamellar body fraction, and intravenous label accumulated in both pools. Using a tracer analysis for non-steady state, we calculated surfactant secretion and clearance rates for the newborn period. Before birth, both rates rose slightly from 1.8 micrograms PL.g body wt-1.h-1 at 6 h before birth to 7.3 at birth. Immediately after birth, secretion rate rose to 37.7 micrograms PL.g body wt-1.h-1. Between 1.5 and 2 h after birth it fell to a minimum of 1.8 micrograms PL.g body wt-1.h-1 and then rose slowly to 6.0 at 12 h. After birth, clearance rate increased less than secretion rate (maximum 24.7 micrograms PL.g body wt-1.h-1 shortly after birth) then followed the same pattern but did not balance secretion rate in the 1st day. .A Stevens PA; Wright JR; Clements JA. .I 201327 .U 90008653 .S J Appl Physiol 9001; 67(4):1623-9 .M Adult; Airway Resistance/PH; Elasticity; Human; Lung/*PH; Male; Mathematics; Models, Biological; Plethysmography, Impedance; Respiration/PH; Respiratory Mechanics/*PH; Support, Non-U.S. Gov't; Tidal Volume; Viscosity. .T Lung impedance in healthy humans measured by forced oscillations from 0.01 to 0.1 Hz. .P JOURNAL ARTICLE. .W Lung impedance was measured from 0.01 to 0.1 Hz in six healthy adults by superimposing small-amplitude forced oscillations on spontaneous breathing. Measurements were made with an almost constant-volume input (160-180 ml) or with an almost constant-flow input (20-30 ml.s-1). No significant difference was found between the two conditions. Lung resistance (RL) sharply decreased from 0.97 kPa.l-1.s at 0.01 Hz to 0.27 kPa.l-1.s at 0.03 Hz and then mildly to 0.23 kPa.l-1.s at 0.1 Hz. Lung effective compliance (CL) decreased slightly and regularly from 0.01 Hz (2.38 l.kPa-1) to 0.1 Hz (1.93 l.kPa-1). The data were analyzed using a linear viscoelastic model adapted from Hildebrandt (J. Appl. Physiol. 28:365-372, 1970) and complemented by a Newtonian resistance (R): RL = R + B/(9.2f); CL = 1/(A + 0.25B + B.log2 pi f), where f is the frequency and B/A is an index of lung tissue viscoelasticity. A good fit was generally obtained, with an average difference of 10% between the observed and predicted values. The ratio B/A was not affected by the breathing and was 10.6 and 13.6% in the constant-volume and constant-flow conditions, respectively, which agrees with Hildebrandt's observations in isolated cat lungs. R was systematically larger than the plethysmographic airway resistance, suggesting that lung tissue resistance might also include a Newtonian component. .A Suki B; Peslin R; Duvivier C; Farre R. .I 201328 .U 90008654 .S J Appl Physiol 9001; 67(4):1630-7 .M Airway Obstruction/*PP; Anoxia/*PP; Human; Hypercapnia/*PP; Male; Respiration/*PH; Sleep/*PH. .T Chemosensitivity and the ventilatory response to airflow obstruction during sleep. .P JOURNAL ARTICLE. .W There is an accumulating body of evidence which suggests that chemical control of breathing can play a role in destabilizing respiratory rhythm during sleep. We hypothesized that the sleeping ventilatory response to hypercapnia (HCVR) and/or hypoxia (HVR) would predict respiratory events following release of inspiratory airway obstruction (IAO) in normal men during non-rapid-eye-movement (NREM) sleep. We therefore measured HCVR, HVR, and ventilation for three breaths preceding and eight breaths following three totally obstructed inspirations in eight normal subjects during NREM sleep. After IAO, we generally observed transient hyperventilation that resulted in hypocapnia and prolonged expiratory time. We found the initial increase in inspiratory minute ventilation (VI) following IAO to be correlated with HCVR (r = 0.72, P less than 0.05) but not HVR. In addition, the maximum decrease in PCO2 below base line was also related to HCVR (r = 0.83, P less than 0.05). This decrement in PCO2 predicted the subsequent prolongation in expiratory time (TE, r = 0.83, P less than 0.05) that was frequently observed. HCVR tended to predict the prolongation of TE, at the nadir of CO2 (r = 0.69, P = 0.057). In conjunction with this hypocapnia and prolongation of TE, hypoventilation with falling VI was often observed followed by periodic hyper- and hypoventilation. These results suggest that high HCVR may result in ventilatory overshoot following IAO and may contribute to ventilatory instability during sleep. .A Gleeson K; Zwillich CW; White DP. .I 201329 .U 90008655 .S J Appl Physiol 9001; 67(4):1638-42 .M Acetyl CoA Carboxylase/ME; Adipose Tissue/ME; Aging/*ME; Animal; ATP Citrate Lyase/ME; Fatty Acid Synthetase Complex/ME; Fatty Acids/BI; Glucosephosphate Dehydrogenase/ME; Glycerides/BI; Glycerophosphates/ME; Lipids/*ME; Lipoprotein Lipase/ME; Liver/ME; Malate Dehydrogenase/ME; Male; Physical Conditioning, Animal/*; Rats; Rats, Inbred F344; Support, U.S. Gov't, P.H.S.. .T Influence of age and exercise training on lipid metabolism in Fischer-344 rats. .P JOURNAL ARTICLE. .W The influence of training on fatty acid and glyceride synthesis by liver and adipose tissue homogenates of young and old Fischer-344 rats was examined. Four groups of rats (10 animals/group) were studied: young untrained, young trained, old untrained, and old trained. Training of each group was for 10 wk at 75% maximal O2 uptake. Young rats were killed at 6 mo of age and old rats were killed at 27 mo of age. Fatty acid synthesis was assessed by measuring the activities of acetyl-CoA carboxylase, fatty acid synthase, ATP citrate-lyase, "malic" enzyme, and glucose-6-phosphate dehydrogenase. Glyceride synthesis was evaluated by determining the rate of incorporation of [14C]glycerol 3-phosphate into lipids. In addition, lipoprotein lipase activity was measured in acetone-ether powders of adipose tissue from the four groups of rats. In liver, training had no effect on fatty acid or glyceride synthesis in either group. However, aging caused a significant decrease in the activities of four of the lipogenic enzymes but had no effect on glyceride synthesis. Training caused an increase in fatty acid synthase and glyceride synthesis in adipose tissue, and aging decreased lipoprotein lipase activity. It was concluded that training enhances the synthetic capacity of lipids by adipose tissue but that aging had a more profound effect in that the activities of the enzymes involved in these processes were lower in the old rats. Furthermore, the decreased activity of lipoprotein lipase in the older rats may explain the higher plasma triglyceride levels that were observed in these animals. .A Barakat HA; Dohm GL; Shukla N; Marks RH; Kern M; Carpenter JW; Mazzeo RS. .I 201330 .U 90008656 .S J Appl Physiol 9001; 67(4):1643-8 .M Adipose Tissue; Adult; Body Composition/*; Body Weight; Caloric Intake; Electric Conductivity; Electrodes; Exercise; Human; Male; Regression Analysis. .T Sensitivity of bioelectrical impedance to detect changes in human body composition [see comments] .P JOURNAL ARTICLE. .W The purpose of this study was to compare the estimates of lean body mass (LBM) and percent body fat (%BF), as predicted by bioelectrical impedance (BIA) and sum of skinfolds (SF), with those derived by hydrostatic weighing (HW) obtained before and after a 10-wk diet and exercise regimen. The experimental (E) group consisted of 17 healthy male subjects; 20 healthy males served as the control (C) group. Post hoc Scheffe contrasts computed on E group data indicated that, for both LBM and %BF, the Lukaski and Segal BIA equations, as well as the Durnin SF equation, derived mean values that were not significantly different (0.05 significance level) from HW in both pre- and postregimen conditions. For LBM, the same equations derived the following significant (P less than 0.01) correlation coefficients for both pre- and postregimen data: Lukaski, 0.87 and 0.85; Segal, 0.89 and 0.87; and Durnin, 0.90 and 0.88. For %BF, the correlation coefficients were slightly lower but remained statistically significant (P less than 0.01). The findings of this study suggest that the BIA method, by use of either the Lukaski or Segal prediction equations, is a valid means of predicting changes in human body composition as measured by the Siri transformation of body density. .A Ross R; Leger L; Martin P; Roy R. .I 201331 .U 90008657 .S J Appl Physiol 9001; 67(4):1649-54 .M Airway Resistance/PH; Animal; Bronchi/PH; Dogs; Human; Respiration/*PH; Respiratory Airflow/*PH; Respiratory Mechanics/*PH; Support, U.S. Gov't, P.H.S.; Trachea/PH. .T Flow distribution through human and canine airways during inhalation and exhalation. .P JOURNAL ARTICLE. .W Airflow distribution through the tracheobronchial tree is influenced by many factors. In a hollow cast of the central airways, the only factors involved are resistance and inertia of the airflow. Distribution of steady flow during both inhalation and exhalation was measured at different total flow rates in human and canine tracheobronchial casts. The resulting airflow rates in peripheral segments were measured with a sensitive apparatus, which did not disturb the distribution of flow. Inertia of the airflow was found to be small but significant in airways of the human cast and substantially greater in the canine airway cast than in the human cast during inhalation. The influence of airflow inertia during inhalation was largely responsible for the different distributions of flow during inhalation and exhalation through the airway casts. Airflow resistance was found to be considerably greater during exhalation and may have contributed to the redistribution of flow. The forces involved are small but should be considered when modeling the in vivo distribution of airflow. .A Briant JK; Cohen BS. .I 201332 .U 90008659 .S J Appl Physiol 9001; 67(4):1662-9 .M Human; Infant; Lung Diseases, Obstructive/PP; Pressure; Respiratory Airflow/*PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Thorax. .T A new technique to demonstrate flow limitation in partial expiratory flow-volume curves in infants. .P JOURNAL ARTICLE. .W Partial expiratory flow-volume (PEFV) curves in infants are generated by applying a compressive pressure over the chest wall with an inflatable jacket. This study addresses two issues: pressure transmission to and across the chest wall and whether flow limitation can be identified. Eleven infants sedated with chloral hydrate were studied. Pressure transmission to the chest wall, measured with neonatal blood pressure cuffs placed on the infant's body surface, was 72 +/- 4% of jacket pressure during compression maneuvers. The pressure transmission to the air spaces, determined by measuring airway pressure during a compression maneuver against an occluded airway, was 56 +/- 6% of jacket pressure. A significant amount of the applied pressure is therefore lost across both the jacket and chest wall. Rapid pressure oscillations (RPO) were superimposed on static jacket pressures while expiratory flow was measured. Absence of associated oscillations of flow measured at the mouth was taken to indicate that flow was independent of driving pressure and therefore limited. Flow limitation was demonstrable with the RPO technique in all infants for jacket pressures greater than 50 cmH2O; however, it was evident at jacket pressures less than 30 cmH2O jacket pressure in four infants with obstructive airway disease. The RPO technique is a useful adjunct to the compression maneuver utilized to generate PEFV curves in infants because it facilitates the recognition of expiratory flow limitation. .A Ratjen F; Zinman R; Wohl ME. .I 201333 .U 90008660 .S J Appl Physiol 9001; 67(4):1670-86 .M Argon/*ME; Diffusion; Heat; Helium/*ME; Human; Mathematics; Models, Biological/*; Permeability; Regional Blood Flow/PH; Skin/*BS; Skin Absorption/*PH; Support, U.S. Gov't, Non-P.H.S.; Xenon/*ME. .T Permeation of inert gases through human skin: modeling the effect of skin blood flow. .P JOURNAL ARTICLE. .W We present an analytic method for determining the effects of skin perfusion--vasculature and flow rates--on the flux of inert gases through human skin. We systematically specify the underlying blood flow and examine the resulting fluxes of several gases, allowing for the appropriate tissue resistances. For physiological flows, the stratum corneum has an effect equivalent to a series resistance. Helium flux at low total flow depends primarily on subdermal perfusion, but at higher flow, middermal and subpapillary effects become important. The fluxes of less permeable gases, such as argon and xenon, depend on middermal and subpapillary flow at lower total flows. From any single measurement of gas flux, it is difficult to establish an unambiguous value for the underlying blood flow, but the simultaneous measurement of different gases narrows the range of plausible conditions. .A Whang JM; Quinn JA; Graves DJ; Neufeld GR. .I 201334 .U 90008661 .S J Appl Physiol 9001; 67(4):1687-91 .M Animal; Blood Circulation/*PH; Microcomputers/*; Respiration, Artificial/*IS; Respiratory Function Tests/*IS; Software. .T A computerized respiratory system including test functions of lung and circulation. .P JOURNAL ARTICLE. .W The design of a microcomputer-controlled ventilator for automatic performance of lung function and circulatory tests has been described. It incorporates the characteristics of normal mechanical ventilation and also allows one to perform a multitude of test procedures for lung function and circulatory studies in paralyzed animals. The major components of the setup are a pump assembly with solenoid valves to direct gas flow, an electromechanical servo system, and a MS-DOS microcomputer system. The pump assembly has been constructed as a relatively simple device. Great versatility is created by the use of a microcomputer for the control of the ventilator. The software can be easily adapted to several other types of experimental studies. Besides the keyboard input the ventilator can be controlled by a remote computer system. This allows one to run an experimental protocol automatically and to use it in closed-loop servo ventilation. The flexibility in the choice of the respiratory parameters makes the ventilator suitable for lung function and circulatory studies during artificial ventilation. The ventilator has been successfully used in different animal studies during the last 6 yr. .A Jansen JR; Hoorn E; Van Goudoever J; Versprille A. .I 201335 .U 90008662 .S J Appl Physiol 9001; 67(4):1692-8 .M Biomechanics; Bone and Bones/PH; Equipment and Supplies/*; Evaluation Studies; Locomotion/*PH; Muscles/PH; Support, U.S. Gov't, P.H.S.; Tendons/PH. .T A treadmill-mounted force platform. .P JOURNAL ARTICLE. .W Muscle, bone, and tendon forces; the movement of the center of mass, and the spring properties of the body during terrestrial locomotion can be measured using ground-mounted force platforms. These measurements have been extremely time consuming because of the difficulty in obtaining repeatable constant speed trials (particularly with animals). We have overcome this difficulty by mounting a force platform directly under the belt of a motorized treadmill. With this arrangement, vertical force can be recorded from an unlimited number of successive ground contacts in a much shorter time. With this treadmill-mounted force platform it is possible to accurately make the following measurements over the full range of steady speeds and under various perturbations of normal gait: 1) vertical ground reaction force over the course of the contact phase; 2) peak forces in bone, muscle, and tendon; 3) the vertical displacement of the center of mass; and 4) contact time for the limbs. In our treadmill-force platform design, belt forces and frictional forces cause no measurable cross-talk problem. Natural frequency (160 Hz), nonlinearity (less than 5%), and position independence (less than 2%) are all quite acceptable. Motor-caused vibrations are greater than 150 Hz and thus can be easily filtered. .A Kram R; Powell AJ. .I 201336 .U 90008663 .S J Appl Physiol 9001; 67(4):1699-703 .M Adult; Aging/ME; Breath Tests/*MT; Comparative Study; Female; Human; Male; Middle Age; Neon/DU; Pulmonary Alveoli/*PH; Pulmonary Gas Exchange/*PH; Support, U.S. Gov't, P.H.S.; Vital Capacity. .T Display of the alveolar plateau of single-breath tests in "dilution index" format. .P JOURNAL ARTICLE. .W In 1949, Fowler (J. Appl. Physiol. 2: 283-299) advocated calculation of a "dilution index" from data of the alveolar plateau of single-breath tests; the calculation provides an estimate of the dilution of resident gas in the lung that gave rise to the observed concentrations. In this communication, we show that the calculation can be applied to conventional single-breath tests where O2 is inhaled by air-breathing persons, and we illustrate the principle with vital capacity breaths of a mixture that contained a low concentration of neon. The dilution was approximately 3:1 in young subjects (20-30 yr), as if a vital capacity of 6 liters were mixed with a residual volume of 2 liters. The dilution was less, 2:1, in older subjects (56 yr) and tended to become as low as 1:1 during emptying of the closing volume. In addition to being more informative, the dilution index format allows common sense comparison of alveolar plateau levels and slopes when single-breath tests are done by various methods. .A Van Liew HD; Mahajan RK. .I 201337 .U 90008944 .S J Bone Joint Surg [Am] 9001; 71(9):1280-8 .M Acute Disease; Adolescence; Adult; Child; Dislocations/SU/*TH; Female; Human; Joint Instability/ET; Life Style; Male; Pain; Patient Education; Postoperative Complications; Sternoclavicular Joint/*/AH/SU. .T Spontaneous atraumatic anterior subluxation of the sternoclavicular joint. .P JOURNAL ARTICLE. .W We reviewed the cases of thirty-seven young patients, ten to thirty-six years old, who had had spontaneous atraumatic anterior subluxation of the sternoclavicular joint. Sudden atraumatic subluxation is quite alarming to the patient and the physician. Twenty-nine of the thirty-seven patients were treated non-operatively by observation and rehabilitative measures. Eight patients had been treated elsewhere with attempted operative reconstruction of the sternoclavicular joint or with resection arthroplasty. After an average follow-up of eight years, the twenty-nine patients who were treated non-operatively (group I) had excellent results, with no limitations of activity or changes in life-style. The eight patients who were treated operatively (group II) had numerous problems, including noticeable scars, persistent instability, pain, or limitation of activity that resulted in an alteration in lifestyle. Three of the eight patients had had a resection of the medial portion of the clavicle. Two of them had a second resection and the third patient had a third resection. A thoracic-outlet syndrome developed in this patient and the clavicle had to be totally resected to obtain relief. Since spontaneous atraumatic anterior subluxation of the sternoclavicular joint has a benign natural course, it should not be treated with operative stabilization of the joint. Instead, a conservative approach that includes education and reassurance of the patient will result in an unaltered lifestyle with no limitation of activity and little or no discomfort. .A Rockwood CA Jr; Odor JM. .I 201338 .U 90008945 .S J Bone Joint Surg [Am] 9001; 71(9):1289-96 .M Adult; Aged; Arthritis, Rheumatoid/EP/*SU; Case Report; Consumer Satisfaction; Female; Human; Joint Prosthesis/*; Male; Middle Age; Movement; Osteoarthritis/EP/*SU; Postoperative Care; Prosthesis Design; Shoulder Joint/PH/*SU; Survival Analysis. .T Survivorship of unconstrained total shoulder arthroplasty. .P JOURNAL ARTICLE. .W The results of fifty-three unconstrained (Neer-II or Gristina) total shoulder arthroplasties were reviewed with the use of survivorship analysis. Failure was defined as the need for revision or the onset of the patient's dissatisfaction. The method of survivorship analysis is presented in detail. Fifty-one total shoulder arthroplasties were followed for a minimum of two years (average, sixty-seven months). The results are reported with the use of the American Shoulder and Elbow Surgeons' rating form. After eleven years, the survivorship was 73 per cent for all prostheses, 71 per cent for the Neer prostheses, and 92 per cent for all prostheses in patients who had rheumatoid arthritis. Data on survivorship of the Gristina prosthesis were available after four years only, at which time it was 100 per cent. The relief of pain, which was the primary reason for the operation, was good or excellent in 82 per cent, improved in 6 per cent, and poor in 12 per cent of the shoulders in these patients. .A Brenner BC; Ferlic DC; Clayton ML; Dennis DA. .I 201339 .U 90008946 .S J Bone Joint Surg [Am] 9001; 71(9):1297-307 .M Animal; Cartilage, Articular/AN/CY/*TR; Comparative Study; Dogs; Female; Freezing; Glycosaminoglycans/AN; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; Histocompatibility Testing/*; Male; Radius/*TR; Synovial Membrane/CY/TR; Tissue Preservation/MT; Transplantation, Homologous. .T The fate of articular cartilage after transplantation of fresh and cryopreserved tissue-antigen-matched and mismatched osteochondral allografts in dogs. .P JOURNAL ARTICLE. .W The long-term success of massive osteochondral allografts depends not only on the incorporation of the transplanted articular cartilage. Osteochondral allografts are immunogenic, and, once an immune response is stimulated by exposure to donor cellular antigens, the cartilage becomes vulnerable to direct injury by cytotoxic antibodies or by lymphocytes, or to indirect injury by inflammatory mediators and enzymes induced by the immune response. To clarify the role of histocompatibility antigen-matching on the health of transplanted articular cartilage, we orthotopically implanted canine leukocyte antigen-matched and mismatched proximal osteochondral allografts of the radius, both fresh and cryopreserved, in beagles. Four groups of dogs received: (1) canine leukocyte antigen-mismatched frozen allografts, (2) canine leukocyte antigen-mismatched fresh allografts, (3) canine leukocyte antigen-matched fresh allografts, or (4) canine leukocyte antigen-matched frozen allografts. In twelve of the dogs, the contralateral leg was subjected to a sham operation, and in ten of the dogs, the proximal part of the radius was removed and replaced as an autogenous graft control. All animals were followed for eleven months after the operation and then were killed. The cartilage of the grafts was evaluated grossly, histologically, and biochemically. The biochemical analysis consisted of measurement of dry weight, content of glycosaminoglycan and hydroxyproline, and galactosamine-to-glucosamine ratios. Analyses of variance were used to study the effect of tissue antigen-matching and freezing on degradation of cartilage. During the study, no dog had grossly obvious clinical abnormalities, all host-graft interfaces healed, and no joints dislocated. The gross appearance of the cartilage was normal for both the joints that had an autogenous graft and those that were subjected to the sham operation. The cartilage of all allografts was thinned, dull, and roughened. The synovial membrane of all of the joints that had been operated on was mildly fibrotic and hyperplastic, but only that of the dogs that had an allograft was severely fibrotic and hyperplastic and demonstrated an inflammatory response. The inflammatory response was most severe in joints that had received a fresh canine leukocyte antigen-mismatched allograft. Invasive pannus was more frequent in joints that had received a fresh graft, particularly those that had received a canine leukocyte antigen-mismatched allograft, and cartilage was sometimes eroded to subchondral bone. Freezing was harmful to the cartilage. Very few cells survived the freezing procedure, and frozen grafts received s significantly worse histological scores had significantly less glycosaminoglycans and had a lower ratio of galactosamine to glucosamine than fresh grafts. .A Stevenson S; Dannucci GA; Sharkey NA; Pool RR. .I 201340 .U 90008947 .S J Bone Joint Surg [Am] 9001; 71(9):1308-13 .M Adult; Bone Transplantation; Bone Wires; Female; Human; Male; Middle Age; Orthopedic Fixation Devices/*; Postoperative Complications/ET; Pseudarthrosis/ET; Scoliosis/RA/*SU; Transplantation, Autologous. .T Adult idiopathic scoliosis treated with Luque or Harrington rods and sublaminar wiring. .P JOURNAL ARTICLE. .W We reviewed the results of spinal arthrodesis that was performed, with sublaminar wires that were attached to either double L-shaped Luque rods or to a Harrington rod, in forty-two adults who had idiopathic scoliosis. The minimum length of follow-up was two years; the maximum, five years; and the average, three years. The average scoliosis measured 67 degrees preoperatively, was corrected to 37 degrees at operation, and was 44 degrees at the time of follow-up. The final correction averaged 34 per cent. A single Harrington rod and multiple sublaminar wires were used in thirty-one patients. Eighteen of the thirty-one patients had a posterior arthrodesis only and thirteen, a preliminary anterior arthrodesis followed by a posterior arthrodesis. Eleven patients had instrumentation with double L-shaped Luque rods; six of them had posterior arthrodesis only and five, a preliminary anterior arthrodesis followed by a posterior arthrodesis. One patient had neurological deficit that was related to the operation. Three patients had a pseudarthrosis, which was in the lumbar area in all of them. All three patients had had only a posterior operation. No statistically significant difference in the amount of final correction was demonstrated between the subgroups. .A Winter RB; Lonstein JE. .I 201341 .U 90008948 .S J Bone Joint Surg [Am] 9001; 71(9):1314-23 .M Adolescence; Adult; Bone Transplantation/*; Child; Child, Preschool; Debridement; Drug Therapy, Combination; Female; Follow-Up Studies; Human; Isoniazid/AD; Kyphosis/ET/*SU; Male; Random Allocation; Rifampin/AD; Spinal Fusion/*MT; Tuberculosis, Spinal/CO/DT/*SU. .T Progression of kyphosis in tuberculosis of the spine treated by anterior arthrodesis. .P JOURNAL ARTICLE. .W The case of eighty-one patients who had tuberculosis of the spine that was treated by debridement and anterior arthrodesis were reviewed eight years or more postoperatively. We studied the progression of the kyphosis and evaluated the function and fate of the bone grafts that were used. At eight years, the results with respect to the progression of the kyphosis were classified as excellent or good in forty-eight patients (59 per cent), all of whom had had minimum destruction of the vertebral bodies; limited surgical excision of bone, resulting in a small post-debridement defect that needed only a short graft; marked intraoperative correction of the deformity; and involvement of lower lumbar segments. Fifteen patients (19 per cent) had a fair result and eighteen (22 per cent), a poor result. An increase in the deformity was common in patients who had extensive involvement of the vertebral bodies that had resulted in a large post-debridement defect necessitating a graft spanning more than two disc spaces. Lesions of the thoracic vertebrae were associated with many of the poor results, and patients who had a marked kyphosis before treatment also did not do well. A stable graft that provided structural support was observed in only thirty-three patients (41 per cent), and failure of the graft due to slippage, fracture, absorption, or subsidence was seen in forty-eight patients (59 per cent). The length of the graft also played a role: the graft failed most often in patients in whom it spanned more than two disc spaces. We concluded that it is unwise to rely solely on the graft to prevent vertebral collapse in patients in whom the length of the graft exceeds two disc spaces. These patients may benefit from additional measures, such as an extended period of non-weight-bearing, posterior arthrodesis after six to twelve weeks, and prolonged use of a brace until complete consolidation is evident. .A Rajasekaran S; Soundarapandian S. .I 201342 .U 90008949 .S J Bone Joint Surg [Am] 9001; 71(9):1324-31 .M Adolescence; Adult; Aged; Bone Nails/*; Debridement; Female; Femoral Fractures/PP/RA/*SU; Fracture Fixation, Intramedullary/*IS; Fractures, Open/CL/PP/*SU; Human; Irrigation; Male; Middle Age; Retrospective Studies; Time Factors; Wound Healing. .T Intramedullary nailing of open fractures of the femoral shaft. .P JOURNAL ARTICLE. .W The cases of eighty-six patients in whom eighty-nine open fractures of the femoral shaft had been treated by intramedullary nailing with reaming were retrospectively reviewed. Twenty-seven fractures were classified as grade-I open fractures; sixteen, as grade-II open fractures; and forty-six, as grade-III open fractures. Immediate intramedullary nailing was done for fifty-six fractures, and delayed stabilization (five to seven days after delayed closure of the wound) was done for thirty-three fractures. A prerequisite for immediate intramedullary nailing was that irrigation and debridement of the open wound be done within eight hours after injury. All fractures healed in an average of 5.2 months. No infections occurred in the sixty-two grade-I, grade-II, or grade-IIIA open fractures, regardless of whether immediate or delayed intramedullary nailing was performed. Of the twenty-seven grade-IIIB fractures, infection developed in three: in one after immediate intramedullary nailing and in two after delayed intramedullary nailing. We concluded that, if a thorough and timely debridement can be accomplished, immediate intramedullary nailing of grade-I and grade-II open fractures of the femoral shaft does not increase the risk of postoperative infection. Selected patients who have a grade-III open fracture may be candidates for immediate intramedullary stabilization, depending on the degree of the patient's associated injuries and the extent of disruption and contamination of the soft tissues of the thigh. .A Brumback RJ; Ellison PS Jr; Poka A; Lakatos R; Bathon GH; Burgess AR. .I 201343 .U 90008950 .S J Bone Joint Surg [Am] 9001; 71(9):1331-6 .M Animal; Blood Pressure; Bone Cements/TU; Cardiovascular Diseases/PC/PP; Comparative Study; Dogs; Embolism, Fat/PC; Hip Prosthesis/*; Irrigation/*MT; Pressure; Pulmonary Artery/PH; Pulmonary Circulation; Support, Non-U.S. Gov't; Vascular Resistance. .T High-volume, high-pressure pulsatile lavage during cemented arthroplasty. .P JOURNAL ARTICLE. .W To determine the efficacy of high-volume, high-pressure pulsatile lavage in the prevention of cardiopulmonary dysfunction and fat embolism during cemented arthroplasty, we studied twenty-eight mongrel dogs that had had a bilateral cemented arthroplasty. Significant increases in pulmonary-artery pressure and pulmonary vascular resistance, accompanied by decreases in arterial oxygen tension and increases in intrapulmonary shunt fraction (Qs/Qt), characterized cardiopulmonary dysfunction after bilateral cemented arthroplasty when no lavage was used. Low-volume, low-pressure manual lavage did not significantly alter these physiological changes, but there was a significant reduction in the number of fat emboli that were demonstrated in the lungs as compared with the no-lavage group. High-volume, high-pressure pulsatile lavage of the intramedullary cavity after reaming significantly reduced the changes in pulmonary-artery pressure, pulmonary vascular resistance, arterial oxygen tension, and intrapulmonary shunt fraction (Qs/Qt). In the pulsatile-lavage group, the number of fat microemboli that were found in the lungs was reduced to 25.7 per cent of those found in the no-lavage group. We concluded that meticulous high-volume, high-pressure pulsatile lavage reduces both pulmonary physiological derangements and fat emboli during bilateral cemented arthroplasty in dogs. .A Byrick RJ; Bell RS; Kay JC; Waddell JP; Mullen JB. .I 201344 .U 90008951 .S J Bone Joint Surg [Am] 9001; 71(9):1337-42 .M Adult; Alloys/*AE; Case Report; Corrosion; Female; Femur Head; Hip Prosthesis/*; Human; Male; Middle Age; Osteolysis/*ET/RA; Prosthesis Failure; Reoperation; Synovial Membrane/PA; Titanium/*AE. .T Aseptic loosening in total hip arthroplasty secondary to osteolysis induced by wear debris from titanium-alloy modular femoral heads [see comments] .P JOURNAL ARTICLE. .W Since 1984, we have used components made of titanium alloy for total joint arthroplasty. Recently, two patients needed revision hip arthroplasty, approximately three years after the initial procedure, because of aseptic loosening secondary to severe osteolysis that had been induced by metallic debris. Although implants made of titanium alloy have many favorable qualities--most importantly, superb biocompatibility--the alloy is more susceptible to wear by particles of acrylic cement and tends to generate more polyethylene wear than do components made of stainless steel or chromium-cobalt. A new process of implanting ions has reportedly improved resistance to wear as well as fatigue properties and has enhanced the resistance to corrosion of the implants. Although, to our knowledge, only in vitro studies of this process have been reported to date, we recommend avoiding the use of components made of titanium alloy in which ions have not been implanted. We suggest considering the possibility of osteolysis secondary to appreciable metallic debris in patients who have aseptic loosening of titanium-alloy components that were not implanted with ions. .A Lombardi AV Jr; Mallory TH; Vaughn BK; Drouillard P. .I 201345 .U 90008952 .S J Bone Joint Surg [Am] 9001; 71(9):1343-7 .M Aged; Cadaver; Comparative Study; Fluoroscopy/*; Human; Knee Joint/*RA; Knee Prosthesis/*; Male; Support, Non-U.S. Gov't; Technology, Radiologic. .T A comparison of plain and fluoroscopically guided radiographs in the assessment of arthroplasty of the knee. .P JOURNAL ARTICLE. .W A cadaver model was used to compare the sensitivity of fluoroscopically guided radiographs with that of plain radiographs in revealing lucent lines beneath the tibial component of an uncemented total knee arthroplasty and subsidence of the component. Fluoroscopically guided radiographs allowed accurate measurement of a lucent line that was one millimeter wide. Plain radiographs were inadequate for the detection and measurement of these lucent lines, leading to inaccuracy. Fluoroscopically guided radiographs also allowed measurement of the distance between the tibial component and radiopaque markers in the proximal part of the tibial metaphysis that was reproducible to within one-half millimeter. Plain radiographs did not provide a reproducible measurement of this distance. The relatively simple technique of fluoroscopically guided radiography is recommended to detect the presence and progression of radiolucent lines and the subsidence of uncemented tibial components after total knee arthroplasty. .A Mintz AD; Pilkington CA; Howie DW. .I 201346 .U 90008953 .S J Bone Joint Surg [Am] 9001; 71(9):1348-54 .M Adolescence; Adult; Aged; Aged, 80 and over; Casts, Surgical; Child; Child, Preschool; Female; Fracture Fixation, Internal; Human; Joint Instability/ET; Male; Middle Age; Retrospective Studies; Splints; Ulna Fractures/CL/RA/*TH. .T Fractures of the coronoid process of the ulna. .P JOURNAL ARTICLE. .W A review of thirty-five patients who had a fracture of the coronoid process of the ulna revealed three types of fracture: Type I--avulsion of the tip of the process; Type II--a fragment involving 50 per cent of the process, or less; and Type III--a fragment involving more than 50 per cent of the process. A concurrent dislocation or associated fracture was present in 14, 56, and 80 per cent of these patients, respectively. The outcome correlated well with the type of fracture. According to an objective elbow-performance index used to assess the results for the thirty-two patients who had at least one year of follow-up (mean, fifty months), 92 per cent of the patients who had a Type-I fracture, 73 per cent who had a Type-II fracture, and 20 per cent who had a Type-III fracture had a satisfactory result. Residual stiffness of the joint was most often present in patients who had a Type-III fracture. We recommend early motion within three weeks after injury for patients who have a Type-I or Type-II fracture. Reduction and fixation, followed by early motion when possible, may be the preferred treatment for patients who have a Type-III fracture. .A Regan W; Morrey B. .I 201347 .U 90008954 .S J Bone Joint Surg [Am] 9001; 71(9):1355-62 .M Adult; Aged; Aged, 80 and over; Arthrodesis/*; Female; Follow-Up Studies; Hip Joint/RA/*SU; Hip Prosthesis/*; Human; Knee Prosthesis/*; Male; Middle Age; Osteoarthritis/SU; Osteoarthritis, Hip/SU; Postoperative Complications/ET. .T Contralateral total hip arthroplasty or ipsilateral total knee arthroplasty in patients who have a long-standing fusion of the hip. .P JOURNAL ARTICLE. .W We studied the cases of twenty patients who had had an ipsilateral total knee arthroplasty or a contralateral total hip arthroplasty, or both, long after one hip had been fused in an acceptable position. Between 1972 and 1986, we performed twenty-one total joint arthroplasties (on thirteen hips and eight knees) and followed two additional patients (one hip and one knee) in whom the operation had been performed elsewhere. The average age of the patients at the time of arthroplasty was fifty-seven years (range, thirty-one to eighty-one years), and the average time from arthrodesis to arthroplasty was thirty-two years (range, eleven to fifty-four years). The results of eighteen of the twenty-three arthroplasties were evaluated at an average of seven years and nine months postoperatively. Four of the remaining five patients, who were followed for an average of eight years, died of a cause that was unrelated to the arthroplasty. After the hip arthroplasty, five hips were rated excellent; five, good; one, fair; and three, poor. Each hip that had a poor result was revised twice for mechanical loosening. Three hips for which the result was not considered poor had progressive radiolucency. After the knee arthroplasty, three knees were rated excellent; four, good; one, fair; and one, poor (because of infection). Seven knees were manipulated a total of fifteen times. Only one patient had progressive symptomatic radiolucency, nine years after the insertion of a posterior stabilized prosthesis. Clinically important ligamentous instability was not encountered.(ABSTRACT TRUNCATED AT 250 WORDS) .A Garvin KL; Pellicci PM; Windsor RE; Conrad EU; Insall JN; Salvati EA. .I 201348 .U 90008955 .S J Bone Joint Surg [Am] 9001; 71(9):1363-70 .M Animal; Dogs; Immobilization/*; Menisci, Tibial/CY/IN/*PH; Neovascularization; Orthopedic Fixation Devices; Support, U.S. Gov't, Non-P.H.S.; Synovial Membrane/TR; Wound Healing/*. .T Experimental models to promote healing of tears in the avascular segment of canine knee menisci. .P JOURNAL ARTICLE. .W Longitudinal tears were created in canine lateral menisci and techniques were applied to induce healing by removal of a core of tissue from the periphery of the meniscus to the tear or by implantation of a vascularized synovial flap into the tear. The meniscal tears did not heal in knees that were not immobilized, and they healed poorly and sporadically in knees that were immobilized in a cast but bore some weight. However, a higher percentage of tears that were treated by the core-removal or synovial-flap technique healed when the knee was firmly immobilized and weight-bearing was prevented by the use of an external skeletal fixator across the joint for eight to twelve weeks. Neovascularization and access to a source of reparative cells appear to be important in the healing process. .A Gershuni DH; Skyhar MJ; Danzig LA; Camp J; Hargens AR; Akeson WH. .I 201349 .U 90008956 .S J Bone Joint Surg [Am] 9001; 71(9):1370-7 .M Adolescence; Arthrography; Bone Screws/*; Child; Epiphyses, Slipped/*SU; Female; Femur Head/*SU; Follow-Up Studies; Hip Joint/RA; Human; Male; Retrospective Studies. .T Treatment of slipped capital femoral epiphysis with a cannulated-screw technique. .P JOURNAL ARTICLE. .W Sixty patients (eighty hips) who had slipped capital femoral epiphysis were treated by epiphyseodesis with a cannulated-screw technique. Forty-nine patients (sixty-seven hips) were available for follow-up, forty-four (sixty hips) of whom were followed for a minimum of two years. Thirty-five patients (forty-six hips) were followed until the hardware was removed. Of seventy-two hips in which contrast medium was injected, arthrographic results were obtained in three. In these three hips, there was evidence of pre-existing narrowing of the joint space. Four patients (six hips) who did not have evidence of penetration by a screw or guide-wire had evidence of either pre-existing chondrolysis or osteoarthrosis. Chondrolysis did not develop postoperatively in any patient who had no evidence of it preoperatively. .A Koval KJ; Lehman WB; Rose D; Koval RP; Grant A; Strongwater A. .I 201350 .U 90008957 .S J Bone Joint Surg [Am] 9001; 71(9):1378-86 .M Acetabulum/PH; Aged; Case Report; Computer Graphics; Female; Femoral Neck Fractures/*SU; Femur Head/PH; Hip Joint/*PH; Hip Prosthesis/*; Human; Pressure; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Telemetry/MT. .T Contact pressures from an instrumented hip endoprosthesis. .P JOURNAL ARTICLE. .W A pressure-measuring Moore-type endoprosthesis was implanted in a seventy-three-year-old patient who had sustained a displaced fracture of the femoral neck. The measurement and telemetry of contact pressures in the hip began in the operating room, and data were acquired periodically for more than thirty-six months. Unexpectedly high localized contact pressures between the acetabular cartilage and the prosthesis were recorded. Early in the period of recovery, activities such as using a bedpan or performing isometric exercise produced pressures that were close to those recorded during normal walking. The highest pressure, eighteen megapascals, was recorded one year postoperatively, while the patient was rising from a chair. High pressures occurred in the superior and posterior aspects of the acetabulum. .A Hodge WA; Carlson KL; Fijan RS; Burgess RG; Riley PO; Harris WH; Mann RW. .I 201351 .U 90008958 .S J Bone Joint Surg [Am] 9001; 71(9):1386-92 .M Ankle Joint/PH; Arthrodesis; Artificial Limbs; Child; Child, Preschool; Female; Femur/*AB; Gait; Human; Infant; Knee Joint/PH/SU; Male; Movement; Osteotomy/*MT; Retrospective Studies; Tibia/*SU. .T Rotational osteotomy for proximal femoral focal deficiency. .P JOURNAL ARTICLE. .W Thirteen patients who had a proximal femoral focal deficiency and were treated with a rotational osteotomy of the tibia (Van Nes procedure) were evaluated at an average of five years after operation. Five patients needed a repeat osteotomy of the tibia: four because the limb had spontaneously derotated toward the original position and one because the limb had had insufficient rotation at the time of operation. One patient had a disarticulation at the ankle after the first stage of a planned two-stage procedure because the mother was not happy with the child's appearance. In ten limbs, the distal femoral growth plate and epiphysis were removed and in two, the femoral epiphysis and growth plate and the tibial growth plate were removed so that the joint of the prosthetic knee would be positioned at the proper height at the completion of the child's growth. Neither growth plate was removed from one limb, the shorter one in the child who had bilateral involvement. A ten-point grading scale based on use and fit of the prosthesis, gait, range of motion of the ankle, use of external support, and final height of the ankle compared with that of the contralateral knee was used to evaluate the result, which was excellent in six patients, good in four, fair in one, and poor in one. One patient, who had a disarticulation at the ankle, was excluded from the final evaluation. Rotational osteotomy provided good function and acceptable cosmetic appearance in the patients who had unilateral involvement. .A Friscia DA; Moseley CF; Oppenheim WL. .I 201352 .U 90008959 .S J Bone Joint Surg [Am] 9001; 71(9):1392-5 .M Adolescence; Adult; Anesthesia, General; Female; Human; Knee Injuries/*CO/DI/PP; Ligaments, Articular/IN; Male; Movement; Prospective Studies; Tibial Fractures/*CO/DI/TH. .T Injuries of the knee associated with fractures of the tibial shaft. Detection by examination under anesthesia: a prospective study. .P JOURNAL ARTICLE. .W Ligamentous injuries of the ipsilateral knee have been documented in association with 25 to 35 percent of fractures of the femoral shaft. However, to our knowledge, a similar association between ligamentous injuries of the knee and fracture of the tibial shaft has not been studied prospectively. To determine if there was such an association, a prospective study was conducted in which the knees of fifty patients who had a fracture of the ipsilateral tibial shaft of varying severity were examined manually while the patient was under general anesthesia. Eleven patients (22 percent) were found to have sustained an injury to at least one ligament of the knee that resulted in increased laxity of 2+ or more. One knee had dislocated. On the basis of the results of this study, we believe that, after stabilization of a fracture of the tibial shaft, it is essential to examine the knee thoroughly to identify any associated ligamentous injuries. .A Templeman DC; Marder RA. .I 201353 .U 90008960 .S J Bone Joint Surg [Am] 9001; 71(9):1396-9 .M Adult; Ankle Joint/*IN/RA; Case Report; Female; Fractures/*CO/SU; Human; Ligaments, Articular/*IN/SU; Male. .T Unrecognized injuries of the lateral ligaments associated with lateral malleolar fractures of the ankle. .P JOURNAL ARTICLE. .W Of four patients who were treated between May 1985 and November 1987 and who had both a lateral malleolar fracture and a tear of the lateral ligaments of the ipsilateral ankle, three could be followed. The fractured malleolus was treated with rigid internal fixation, but the injury to the lateral ligaments was not diagnosed until the ankle was stressed to test for stability after the internal fixation. We believe that if disruption of the lateral ligaments is noted at operation, repair is indicated. This involves only a slight prolongation of time under anesthesia and markedly increases the chances for a stable ankle. It is important to check intraoperatively for a possible tear of the lateral ligaments in a patient who has a fracture of the ankle, especially when the injury was caused by high-energy trauma. .A Whitelaw GP; Sawka MW; Wetzler M; Segal D; Miller J. .I 201354 .U 90008961 .S J Bone Joint Surg [Am] 9001; 71(9):1400-5 .M Adolescence; Adult; Carpal Bones/*AH/IN/RA; Female; Fractures, Ununited/RA; Human; Male; Middle Age; Osteomalacia/PA/RA; Reference Standards; Reproducibility of Results; Semilunar Bone/PA/RA. .T Determining carpal collapse. An improved method. .P JOURNAL ARTICLE. .W The carpal height index (carpal height ratio of the diseased wrist divided by that of the normal wrist, as described by Kato et al.) was calculated in forty normal subjects, ten patients who had Stage-III lunatomalacia, and eight patients who had non-union of a fracture of the scaphoid. The method of Youm et al. for determining the carpal height index was altered to include the use of defined points of reference and a standardized radiographic technique. Two tests of reproducibility demonstrated the reliability of the method. The carpal height index was found to be superior to the carpal height ratio for the evaluation of unilateral disease. The mean carpal height index of diseased wrists differed significantly from that of normal wrists. The carpal height index (for unilateral disease) or the carpal height ratio (for bilateral disease) can be used to describe the progression of collapse of the wrist quantitatively and to evaluate and compare various forms of treatment. .A Stahelin A; Pfeiffer K; Sennwald G; Segmuller G. .I 201355 .U 90008962 .S J Bone Joint Surg [Am] 9001; 71(9):1406-7 .M Case Report; Femur Head Necrosis/SU; Hip Dislocation/*CO/SU; Hip Prosthesis/*; Human; Male; Middle Age; Prosthesis Failure; Reoperation. .T Displacement of an uncemented femoral component after dislocation of a total hip replacement. A case report [see comments] .P JOURNAL ARTICLE. .A Friedman RJ. .I 201356 .U 90008963 .S J Bone Joint Surg [Am] 9001; 71(9):1408-9 .M Aneurysm/*CO/DI; Case Report; Groin; Human; Iliac Artery/*; Male; Middle Age; Nerve Compression Syndromes/*ET/PP; Obturator Nerve/*; Pain; Thigh. .T Obturator neuropathy caused by an aneurysm of the hypogastric artery. A case report. .P JOURNAL ARTICLE. .A Kleiner JB; Thorne RP. .I 201357 .U 90008964 .S J Bone Joint Surg [Am] 9001; 71(9):1410-1 .M Case Report; Female; Human; Knee; Magnetic Resonance Imaging; Middle Age; Neurilemmoma/*DI/PP/SU; Pain; Peripheral Nerve Neoplasms/*DI/PP/SU; Thigh/*IR. .T Neurilemoma of the saphenous nerve presenting as pain in the knee. A case report. .P JOURNAL ARTICLE. .A Edwards JC; Green CT; Riefel E. .I 201358 .U 90008965 .S J Bone Joint Surg [Am] 9001; 71(9):1412-4 .M Adenoma/*CO/DI/SU; Bone Diseases, Metabolic/ET; Case Report; Female; Femur Head Necrosis/*ET/RA; Human; Middle Age; Pituitary Neoplasms/*CO/DI/SU. .T Idiopathic osteonecrosis of the femoral head associated with a pituitary tumor. Report of a case. .P JOURNAL ARTICLE. .A Alexakis PG; Wallack M. .I 201359 .U 90008966 .S J Bone Joint Surg [Am] 9001; 71(9):1414-7 .M Case Report; Hip Fractures/*CO/RA/SU; Hip Prosthesis/*; Human; Male; Middle Age; Pulmonary Embolism/*ET; Risk Factors; Thrombosis/CO/*ET. .T Deep venous thrombosis after trauma to the lower extremity in patients who had a previous arthrodesis of the hip. A report of three cases. .P JOURNAL ARTICLE. .A Hanks GA; Handal JA; Evarts CM. .I 201360 .U 90008967 .S J Bone Joint Surg [Am] 9001; 71(9):1418 .M Adrenal Gland Hypofunction/*CO/DI/DT; Case Report; Female; Hip Joint/*; Human; Hydrocortisone/TU; Joint Diseases/ET; Knee Joint/*; Middle Age. .T An unusual cause of flexion deformity of the hips and knees. A case report. .P JOURNAL ARTICLE. .A Harper WM; Wray CC; Burden AC. .I 201361 .U 90008970 .S J Bone Joint Surg [Am] 9001; 71(9):1429-30 .M Human; Neoplasm Recurrence, Local/PC; Sarcoma/*SU; Soft Tissue Neoplasms/*SU. .T The surgical margin in soft-tissue sarcoma [letter; comment] .P COMMENT; LETTER. .A Rydholm A; Rooser B. .I 201362 .U 90008972 .S J Burn Care Rehabil 9001; 10(4):287-91 .M Burns/*; Human; Societies, Medical/*; Specialties, Medical/*; United States; Wit and Humor. .T The burn doc at 21. Coming of age. .P JOURNAL ARTICLE. .A Ward CG. .I 201363 .U 90008973 .S J Burn Care Rehabil 9001; 10(4):292-9 .M Burns/PP/*TH; Computer Simulation/*; Fluid Therapy/*MT; Human; Models, Biological; Resuscitation/*MT; Support, Non-U.S. Gov't. .T Computer simulation of fluid resuscitation in trauma. First pragmatic validation in thermal injury. .P JOURNAL ARTICLE. .W A comprehensive pathophysiologic model has been designed to describe the fluid shifts and hemodynamics in connection with fluid therapy for patients who have had trauma. The model is used to simulate treatment of a patient with burn injury, and these results are compared with measured physiologic and biochemical variables. Various formulas for resuscitation of patients with thermal injuries are also simulated to illustrate the potential use of the "patient simulator" for designing fluid resuscitation programs. .A Arturson G; Groth T; Hedlund A; Zaar B. .I 201364 .U 90008977 .S J Burn Care Rehabil 9001; 10(4):321-6 .M Adult; Aged; Antibodies, Bacterial/*TU; Blood Gas Monitoring, Transcutaneous; Burns/*CO; Human; Middle Age; Platelet Count; Pseudomonas/*IM; Retrospective Studies; Shock, Septic/ET/*TH; Vascular Resistance. .T Use of Pseudomonas hyperimmunoglobulin to treat septic shock in burn cases. .P JOURNAL ARTICLE. .W The progress of 18 episodes of septic shock in nine patients with burn injuries after administration of a Pseudomonas immunoglobulin is presented. In nine instances the septic shock was treated successfully. The mean burn index of these nine patients was 96. In six of the nine patients the septic shock was accompanied by simultaneous inhalation trauma and in six by acute kidney failure. In four cases the sepsis was caused by P. aeruginosa and in five by staphylococci. Despite the different causative agents, successful treatment was possible in these cases. The mean burn index for the four patients who eventually died was 119; all patients in this group were suffering from an inhalation trauma and acute kidney failure requiring dialysis. In these cases even the use of Pseudomonas immunoglobulin had no decisive effect. .A Kistler D; Piert M; Kauhl W; Hettich R. .I 201365 .U 90008979 .S J Burn Care Rehabil 9001; 10(4):331-5 .M Adolescence; Adult; Bone and Bones/*; Bone Neoplasms/*ET/RI; Burns/*CO; Child; Choristoma/*ET/RI; Exercise Therapy; False Positive Reactions; Human; Immobilization; Joints/*; Middle Age; Retrospective Studies. .T Heterotopic bone formation in the patient with burn injuries. A retrospective assessment of contributing factors and methods of investigation. .P JOURNAL ARTICLE. .W The incidence of heterotopic bone formation in seven of 25 patients with burn injuries who required endotracheal intubation and ventilation for smoke inhalation injury was believed to be unacceptably high. Factors in the affected patients distinguishing them from those unaffected were sought. Total protein levels were found to be higher in the affected group. This may correlate with the calciuretic response to protein loading reported previously. Of the affected patients, four demonstrated extreme agitation and resisted physiotherapy. Only one of the 18 nonaffected patients was equally agitated and resistant (p less than 0.05). The additional joint trauma sustained by the affected patients may contribute to the development of heterotopic bone. In bone scans in 18 consecutive patients deemed to be at risk, all showed increased radioactivity at multiple joints. Only seven patients developed heterotopic bone. Bone scans are not sufficiently specific to be used as a diagnostic tool in detecting heterotopic bone. .A VanLaeken N; Snelling CF; Meek RN; Warren RJ; Foley B. .I 201366 .U 90008980 .S J Burn Care Rehabil 9001; 10(4):336-45 .M Adult; Bicycling/*; Body Temperature/*; Cold; Human; Hydrotherapy/*MT; Male; Oxygen Consumption; Skin Temperature; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.. .T Core temperature response to immersed bicycle ergometer exercise at water temperatures of 21 degrees, 25 degrees, and 29 degrees C. .P JOURNAL ARTICLE. .W A bicycle ergometer modified for aquatic exercise was used to determine the effects of immersion on core temperature during submaximal exercise at different water temperatures. An exercise intensity (60% of maximal oxygen consumption) and duration (30 minutes) considered appropriate for cardiovascular conditioning were used. These data will be useful in cardiovascular and leg-strengthening hydrotherapy programs. Rectal temperature, skin temperature, and a rating of thermal comfort were studied in five normal men (14.8% +/- 5.6% fat) during headout immersion at water temperatures of 21.1 degrees, 25.3 degrees, and 29.4 degrees C and exercise in air of 21.1 degrees C. Subjects were immersed for 30 minutes during static and exercise (63% +/- 0.6% maximal oxygen consumption) conditions. Data were collected every 5 minutes and analyzed by repeated measured analysis of variance. At water temperatures, rectal temperature fell from control during static immersion (p less than or equal to 0.05) and was lower than control at the end of the 30-minute recovery period (p less than or equal to 0.05). During exercise there was no change in rectal temperature at water temperatures of 21.1 degrees and 25.3 degrees C; however, rectal temperature rose at water temperatures of 29.4 degrees (p less than or equal to 0.05) and air 21.1 degrees C (p less than or equal to 0.05). At the end of recovery rectal temperature was lower than control at water temperatures 21.1 degrees C (p less than or equal to 0.05) and greater than control at water temperatures 29.4 degrees C (p less than or equal to 0.05). There was no change from control in rectal temperatures at water temperatures 25.3 degrees C and air at 21.1 degrees C. These results indicate that immersion in 25.3 degrees and 21.1 degrees C water effectively attenuates the rise in rectal temperature during exercise at 63% of maximal oxygen consumption, whereas immersion in 29.4 degrees C water does not. In addition, both skin and rectal temperatures affect perception of thermal state but do not give the subjects an accurate estimation of thermal balance. .A Israel DJ; Heydon KM; Edlich RF; Pozos RS; Wittmers LE Jr. .I 201367 .U 90008981 .S J Burn Care Rehabil 9001; 10(4):346-9 .M Burns/*RH; Exercise Therapy/IS/*MT; Gait; Human; Leg Injuries/*RH. .T Use of a ramp surface for lower extremity exercise with burn-injured patients. .P JOURNAL ARTICLE. .W The use of a ramp surface in our Burn Center has demonstrated benefits in improving gait, standing postures, and lower extremity muscle length. This technique has been effective with a wide age range of patients and is most useful as part of an overall treatment program including prestretching of lower extremities. .A Duncan CE. .I 201368 .U 90008982 .S J Burn Care Rehabil 9001; 10(4):350-1 .M Exercise Therapy/*MT; Fingers/*; Human. .T Creative use of metal rings in hand therapy. .P JOURNAL ARTICLE. .A Strasser M. .I 201369 .U 90008983 .S J Burn Care Rehabil 9001; 10(4):351-3 .M Burns/*RH; Casts, Surgical/*; Cicatrix/*PC; Hand Injuries/*RH; Human. .T Use of positive plaster impressions to facilitate measurement of anti-burn scar support gloves for severely burned hands. .P JOURNAL ARTICLE. .A Ward RS; Schenbly WA; Kravitz M; Warden GD; Saffle JR. .I 201370 .U 90008984 .S J Burn Care Rehabil 9001; 10(4):356-9 .M Aged; Aged, 80 and over; Burns/EP/ET/*PC; Clothing/*; Female; Human; Patient Education. .T Cooking-related burn injuries in the elderly preventing the "granny gown" burn. .P JOURNAL ARTICLE. .W Cooking-related burn injuries accounted for 27% of the elderly female admissions at one burn center. The primary mode of injury was found to be ignition of clothing while reaching across a stove. To develop a prevention program for this problem, biologic and environmental hazards were identified. From this information, a two-phase prevention program was designed. Phase one, education, entailed the development, publication, and distribution of a pamphlet to a variety of local agencies. Phase two, an environment evaluation, consisted of contacting consumer relation departments of major stove manufacturers suggesting a product safety review. The community response to this program has been favorable. Its design should provide the foundation for preventing increased incidence of cooking-related burn injuries. .A Turner DG; Leman CJ; Jordan MH. .I 201371 .U 90008985 .S J Burn Care Rehabil 9001; 10(4):362-73 .M Burns/*; Human; Nursing Care/*ST. .T Standards for burn nursing practice. .P JOURNAL ARTICLE. .A Bayley EW; Braun AE; D'Italia JG; Fitzgerald JM; Gandolfo SL; Hoban-Kahn M; Kaplon S; Lowe KE; McLaughlin JF; McMonigle PA; et al. .I 201372 .U 90008986 .S J Burn Care Rehabil 9001; 10(4):375-8 .M Adult; Burns/*SU; Hemorrhage/*PC; Human; Intraoperative Complications/*PC; Middle Age; Pilot Projects; Vasopressins/*TU. .T Burn excision with intraoperative vasopressin. .P JOURNAL ARTICLE. .W Reducing blood flow to the skin during burn wound excision should decrease blood loss, which remains a major problem during primary excision of large burns. This clinical investigation demonstrates that arginine-vasopressin appears to reduce intraoperative blood loss and is relatively free of complications. This treatment has potential benefits for the patient with small burns as well. The amount of banked blood required could be greatly reduced, thus decreasing the risks of transfusion and the cost of burn care. .A Achauer BM; Hernandez J; Parker A. .I 201373 .U 90008988 .S J Burn Care Rehabil 9001; 10(5):381-7 .M Animal; Burns/PP/*SU; Halothane/*PD; Hemodynamics; Intraoperative Period; Oxygen Consumption/*DE; Postoperative Period; Sheep; Support, U.S. Gov't, P.H.S.. .T Oxygen consumption is increased in the postanesthesia period after burn excision. .P JOURNAL ARTICLE. .W We studied the intraoperative and postoperative effects of anesthesia and wound excision on oxygen delivery and oxygen consumption after burn injury. Twenty adult sheep were studied: six had halothane anesthesia alone and 14 had anesthesia and third-degree burns over 15% of the total body surface. Body temperatures were maintained within 1 degree C of baseline value during the operations. The burns on six sheep were totally excised and hide from donor sheep was grafted 3 hours after injury; in eight sheep, excision and grafting were done 5 days after injury. We found that 3 hours of anesthesia in controls decreased oxygen delivery (DO2) by 22% +/- 6% and oxygen consumption (VO2) by 30% +/- 7% from waking baseline values primarily because of a decrease in cardiac output as oxygen (O2) extraction from hemoglobin also decreased. However, no base deficit developed. DO2 and (VO2) transiently increased to 9% +/- 3% above baseline value on the sheeps' return to the waking state. Anesthesia and wound excision, which began 3 hours after the burns were formed, decreased DO2 and VO2 by 25% +/- 4% and 32% +/- 4%, respectively, despite baseline filling pressures. However, a base deficit of -3 +/- 1 mEq/L developed during the two-hour operations, which began with the administration of anesthesia alone. Oxygen consumption increased to 25% +/- 6% above the waking baseline value upon each subject's return to the waking state. In the sheep treated 5 days after burn injury, DO2 decreased by 35% +/- 6% and VO2 decreased by 42% +/- 6% below the value during the waking hypermetabolic state when the sheep were under anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS) .A Demling RH; Lalonde C. .I 201374 .U 90008989 .S J Burn Care Rehabil 9001; 10(5):388-93 .M Animal; Burns/*ME/PA; Female; Liver/ME; Lung/ME; Phagocytosis/*; Rats; Reticuloendothelial System/*ME; Spleen/ME; Support, Non-U.S. Gov't; Technetium Tc 99m Sulfur Colloid/DU; Tissue Distribution. .T Effect of acute burn trauma on phagocytic activity of the reticuloendothelial system in rats. .P JOURNAL ARTICLE. .W The effect of acute burn trauma on phagocytic activity of the reticuloendothelial system measured in vivo with technetium 99m sulfur colloid was examined in rats subjected to acute burn trauma. After the scald injuries (10-second, full-thickness burns) were induced, a reduction in phagocytic activity by the spleen took place with an accompanying increase in the uptake of colloid material by the lungs. Uptake of colloid material by the liver was essentially unchanged. These uptake changes, observed within hours after the inducement of acute burn trauma and apparently continuing for 7 days after burn injury, may explain, in part, the development of septicemia in patients with burns because altered phagocytic activity of the reticuloendothelial system can result in subsequent overabundance of microorganisms and bacteria in the blood. .A Trop M; Schiffrin EJ; Jung WK; Callahan RJ; Strauss HW; Carter EA. .I 201375 .U 90008990 .S J Burn Care Rehabil 9001; 10(5):394-401 .M Animal; Burns/BL/*IM; Cell Separation; Chemotaxis, Leukocyte/*IM; Flow Cytometry; Hydrogen Peroxide/ME; Kinetics; Male; Membrane Potentials; Neutrophils; Rats; Support, U.S. Gov't, Non-P.H.S.. .T Alteration of rat polymorphonuclear leukocyte function after thermal injury. .P JOURNAL ARTICLE. .W One portion of host defense to bacterial challenge(s) involves the activation and infiltration of endogenous polymorphonuclear leukocytes. Thermal injuries are frequently associated with immunologic abnormalities including alterations of polymorphonuclear leukocyte-associated nonspecific resistance. We examined isolated peripheral rat polymorphonuclear leukocytes for alterations in membrane potential, oxidative capability, and locomotor function after the experimental application of 20% full-thickness body surface area thermal injury. Thermal injury resulted in significant reductions of peripheral red blood cell concentration(s) and increases in leukocyte and platelet concentrations for 42 days after injury. In addition to the quantitative changes, polymorphonuclear leukocytes also demonstrated altered qualitative functions. Compared with phorbol myristate acetate-induced activation of normal cells, polymorphonuclear leukocyte membranes from thermal-injured animals were electrophysiologically less responsive for 3 weeks after injury. The ability of polymorphonuclear leukocytes to produce intracellular H2O2, a measure of oxidative function, was also significantly decreased for 7 days after injury. The paradox in this paradigm of thermal injury was the demonstration of peripheral polymorphonuclear leukocyte quantitative increases with concurrent significant qualitative impairment. Qualitative lesions included altered states of membrane depolarization and depressed oxidative capability that may individually, or collectively, reduce nonspecific immune capabilities of the host to levels that are inadequate to combat infection. .A Gruber DF; D'Alesandro MM. .I 201376 .U 90008991 .S J Burn Care Rehabil 9001; 10(5):402-5 .M Adult; Aged; Burns/*SU; Comparative Study; Hemorrhage/ET; Human; Laser Surgery/*AE; Middle Age; Postoperative Complications; Skin Transplantation; Support, Non-U.S. Gov't; Surgical Instruments; Time Factors. .T Burn excision with contact neodymium: YAG laser. .P JOURNAL ARTICLE. .W The newest laser modality, the contact Neodymium: YAG laser, was compared with the standard steel scalpel in excisions of full-thickness burns. Six patients with deep burns of variable sizes were included in this pilot study. The area to be operated on in each patient was divided into two areas resembling each other as much as possible in size, tissue type, and depth of injury. The results suggest that bleeding was diminished by 44% in contact laser surgery compared with the steel scalpel. Still the difference was not significant. There was no impairment of graft take after laser surgery compared with the steel scalpel. However, the laser method caused a significant increase (p less than 0.02) in operating time. The contact Nd: YAG laser can be recommended for excision of relatively small deep burn injuries, especially in areas in which bleeding is a problem with other methods. .A Hukki J; Harma M; Asko-Seljavaara S; Schroder T. .I 201377 .U 90008992 .S J Burn Care Rehabil 9001; 10(5):406-9 .M Adult; Aged; Burn Units; Burns/*CO; Female; Hemodynamics/DE; Human; Infusions, Intravenous; Male; Methadone/*AD; Middle Age; Pain/*DT/ET. .T Continuous intravenous infusion of methadone for control of burn pain. .P JOURNAL ARTICLE. .W Seventeen patients with acute, severe burns were treated with a two-stage continuous, intravenous infusion of methadone to control pain. An initial loading infusion was run for 2 hours at 0.1 mg/kg/hr of methadone; then a maintenance infusion was continued at 0.01 mg/kg/hr of methadone. Median visual analog scale scores were 70% pain relief after the 2-hour loading infusion and 80% after 24 hours. Cardiovascular parameters were stable. There was a significant decrease in the respiratory rate of the patients. It appears that continuous intravenous methadone is an effective analgesic agent for the patient with acute, severe burns. Administration of the drug should be on an individualized basis with conservative dosing in a well-monitored environment because somnolence and respiratory depression can occur. .A Concilus R; Denson DD; Knarr D; Warden G; Raj PP. .I 201378 .U 90008994 .S J Burn Care Rehabil 9001; 10(5):418-20 .M Administration, Topical; Adolescence; Adult; Burns/CO/*DT; Child; Comparative Study; Female; Human; Leukocyte Count; Leukopenia/*CI/CO; Male; Middle Age; Silver Nitrate/TU; Silver Sulfadiazine/*AE; Sulfadiazine/*AE. .T Leukopenia in acute thermal injury: evidence against topical silver sulfadiazine as the causative agent. .P JOURNAL ARTICLE. .W White blood cell data from time of admission to 4 days after burn injury was retrospectively reviewed to determine differences in the incidence of leukopenia in patients with burn injuries treated topically with either silver sulfadiazine or silver nitrate. WBC counts decreased in both groups of patients during the first 3 days after burn injury. An incidence of leukopenia (WBC count less than or equal to 5000/mm3) was observed in of 40 (47.5%) patients treated with silver sulfadiazine and in 13 of 30 (43.3%) patients treated with silver nitrate. There was no statistical difference in the incidence of leukopenia between the two treatment groups. These data suggest that silver sulfadiazine may not be the cause of the leukopenia observed early after burn injury. .A Thomson PD; Moore NP; Rice TL; Prasad JK. .I 201379 .U 90008995 .S J Burn Care Rehabil 9001; 10(5):421-4 .M Amoxicillin/*TU; Animal; Antibiotics, Combined/*TU; Burns/*CO; Clavulanic Acids/*TU; Comparative Study; Drug Screening; Penicillins/*TU; Rats; Rats, Inbred Strains; Silver Sulfadiazine/*TU; Sulfadiazine/*TU; Ticarcillin/*TU; Wound Infection/*DT. .T Therapeutic efficacy of timentin and augmentin versus silvadene in burn wound infections. .P JOURNAL ARTICLE. .W Successful closure of thermal injuries, by either skin graft or delayed wound closure, largely depends on the ability to control the number of bacteria in the wound. The purpose of this study was to investigate the efficacy of two new antimicrobial agents, ticarcillin and clavulanate (Timentin) and amoxicillin and clavulanate (Augmentin), in the infected thermal injury. The therapeutic results were compared with the model treated with the standard topical silver sulfadiazine (Silvadene). Seventy-six Sprague-Dawley rats received a 20% full-thickness thermal injury and were then divided into six treatment groups. Three of the groups were inoculated topically with 10(8) Pseudomonas aeruginosa/ml, and three of the groups received topical inoculation of 10(8) Staphylococcus aureus/ml. The groups inoculated with P. aeruginosa received either intraperitoneal Timentin, topical Silvadene, or placebo treatment. The groups inoculated with S. aureus were treated with either enteral Augmentin, topical Silvadene, or placebo. The animals received 10 days of therapy and underwent tissue biopsies on alternate days. Statistical analysis showed that the level of bacteria in the wounds compared with the control group was significantly (p less than 0.05) decreased for both antibiotics tested as measured by quantitative wound biopsies. These studies demonstrate the efficacy of systemic Timentin and Augmentin in the infected thermal injury. .A Heggers JP; McHugh T; Zoellner S; Boertman JA; Niu XT; Robson MC; Velanovich V. .I 201380 .U 90008996 .S J Burn Care Rehabil 9001; 10(5):425-8 .M Adult; Aged; Aged, 80 and over; Burns/*ME; Female; Fluoroimmunoassay; Human; Male; Middle Age; Orosomucoid/*AN; Protein Binding; Serum Albumin/*AN; Support, Non-U.S. Gov't; Vancomycin/*ME. .T The influence of serum albumin and alpha 1-acid glycoprotein on vancomycin protein binding in patients with burn injuries. .P JOURNAL ARTICLE. .W Ten patients with burn injuries (mean total body surface area burn = 29% +/- 16) were studied at various points in the course of their burn therapy. Alpha 1-Acid glycoprotein, albumin, and vancomycin concentrations were determined with either a trough or peak vancomycin quantitative determination. Alpha 1-Acid glycoprotein concentrations ranged from 125 to 333 mg/dl and albumin concentrations ranged from 1.7 to 4.2 gm/dl. Vancomycin protein binding, as determined by ultrafiltration, averaged 29% +/- 6%. There was a strong (r = 0.92) relationship between percent protein-bound vancomycin and albumin. There was a poor statistical relationship between percent protein-bound vancomycin and alpha 1-acid glycoprotein (r = 0.28). Alpha 1-Acid glycoprotein appeared to have virtually no effect on the protein-binding characteristics of vancomycin over the range of concentrations studied. .A Zokufa HZ; Solem LD; Rodvold KA; Crossley KB; Fischer JH; Rotschafer JC. .I 201381 .U 90008997 .S J Burn Care Rehabil 9001; 10(5):429-31 .M Aged; Aged, 80 and over; Burns/*/NU; Female; Hospitalization/*; Human; Length of Stay; Male; Medical Records; Middle Age; Nursing Homes/*; Patient Discharge/*; Retrospective Studies. .T Thermal injury in the elderly. The limited need for nursing home care. .P JOURNAL ARTICLE. .W Although it appears that survival has been increased and hospital stays have been decreased in elderly patients with burn injuries, limited information is available on the functional status of these patients at the time of discharge from the hospital. Because this information is necessary to assess more fully the success or failure of current modes of therapy, we have reviewed the records of 99 surviving patients with burn injuries over the age of 55 years. These patients had a mean age 71.8 years and a mean +/- SD burn size of 8.9% +/- 8.6%, with 36 patients having burns over greater than 10% of body surface area and 14 patients having burns over greater than 20%. The mean hospital stay of these patients was 16.9 days, and 75% of the patients required surgery to heal the burn wounds. Since just five (5%) of the 99 patients required nursing home placement at discharge, it appears that the majority of elderly patients with burn injuries recover sufficiently from the injuries to resume their preinjury life-style. .A Keys TC; Moresi JM; Deitch EA. .I 201382 .U 90008998 .S J Burn Care Rehabil 9001; 10(5):432-5 .M Adolescence; Adult; Burns/EC/*TH; Female; Human; Hyperbaric Oxygenation/*MT; Length of Stay/*; Male; Middle Age. .T Adjunctive hyperbaric oxygen therapy reduces length of hospitalization in thermal burns. .P JOURNAL ARTICLE. .W The use of adjunctive hyperbaric oxygen therapy as part of a comprehensive program of burn care at our institution has resulted in a statistically significant reduction in length of hospital stay (p = less than 0.012) with no increase in cost of hospital care in patients suffering burns over 18% to 39% of total body surface area. .A Cianci P; Lueders HW; Lee H; Shapiro RL; Sexton J; Williams C; Sato R. .I 201383 .U 90008999 .S J Burn Care Rehabil 9001; 10(5):436-44 .M Adolescence; Adult; Burns/*CO; Case Report; Child; Child, Preschool; Cicatrix/*ET/PP; Female; Heat; Human; Lasers/DU; Male; Microcirculation; Middle Age; Vasodilation/*. .T Microcirculation in hypertrophic scars after burn injury. .P JOURNAL ARTICLE. .W Hypertrophic scar formation is a common complication after burn injury. Early active scars show hyperemic appearances that change as the scar matures. This is a report on microcirculation in hypertrophic scars after burn injury among 50 Chinese patients with a laser Doppler flowmeter. The average period of follow-up for the patients was 20 months. The microcirculatory response in scars to vasodilation (heat) stimulus was studied. Significant differences (p less than 0.0001) were demonstrated between scars of different clinical grades of maturity when compared with normal skin. The qualitative and quantitative differences in microcirculatory blood flow were correlated with site variations and different physiologic demands from different grades of scars. The study showed that laser Doppler flowmetry was useful in the clinical grading assessment of or for scar maturity. .A Leung KS; Sher A; Clark JA; Cheng JC; Leung PC. .I 201384 .U 90009001 .S J Burn Care Rehabil 9001; 10(5):448-53 .M Adolescence; Adult; Agricultural Workers' Diseases/*CI/PP/TH; Ammonia/*PO; Burn Units; Burns, Chemical/ET/*PP; Case Report; Eye Burns/CI; Human; Length of Stay; Male; Middle Age. .T Anhydrous ammonia injuries. .P JOURNAL ARTICLE. .W Anhydrous ammonia is a relatively common cause of chemical injuries. Most injuries are the result of accidental exposure, frequently in the course of work. Exposure to anhydrous ammonia may produce serious injury to the eyes, respiratory system, and integument. Anhydrous ammonia injuries occurring in a predominantly agricultural region are reviewed. The pathophysiology of anhydrous ammonia injury is reviewed. Therapeutic modalities are described. Guidelines to prevent or minimize injury are delineated. .A Millea TP; Kucan JO; Smoot EC 3d. .I 201385 .U 90009002 .S J Burn Care Rehabil 9001; 10(5):454-61 .M Adolescence; Adult; Body Image/*; Burns/CO/*PX; Depression/ET; Female; Human; Male; Questionnaires; Self Concept/*. .T Body image, self-esteem, and depression in burn-injured adolescents and young adults. .P JOURNAL ARTICLE. .W The present study was conducted to clarify the effects of burn-related variables (specifically, age at time of burn, years elapsed since burn, locus of burn, and percent of total body surface area burned), demographics, and perceived social support variables on psychological adjustment after injury within a well-defined sample. Subjects were 121 patients, currently 14 to 27 years old, burned within the past 10 years. They completed the following: Semantic Differential Measure of Body Image, Rosenberg Self-Esteem Scale, Beck Depression Inventory, Perceived Social Inventory--Friends, and Perceived Social Inventory--Family. The mean age of the subjects was 17.8 years; the mean percent total body surface area burned was 27.3%, with 75% of the subjects having burns on a visible or socially sensitive area. Correlational and multiple regression analyses showed that subjects perceiving more social support (friends more than family) had more positive body images (p less than 0.01), greater self-esteem (p less than 0.01), and less depression (p less than 0.01) than others, with a significant impact from difference in subjects' gender. .A Orr DA; Reznikoff M; Smith GM. .I 201386 .U 90009003 .S J Burn Care Rehabil 9001; 10(5):462-3 .M Burns/*TH; Child; Child, Preschool; Human; Infant; Skin Transplantation/*; Splints/*. .T The Kerlix tongue-depressor splint for skin-grafted areas in burned children. .P JOURNAL ARTICLE. .W A simple, sterile splint to ensure skin take and to immobilize joints in burned children who have grafted wounds is described. It consists of sterile tongue depressors placed 2 to 3 cm apart on the circumference of the limb and entwined at various layers with wrapped Kerlix. In our practice this device is advantageous because of its evaporative properties; it is lightweight and easily removed. .A Kaufman T; Newman RA; Weinberg A; Wexler MR. .I 201387 .U 90009004 .S J Burn Care Rehabil 9001; 10(5):464-8 .M Adult; Affective Disorders/ET/*TH; Burns/CO/*PX; Case Report; Human; Interpersonal Relations; Male; Marriage; Volition/*. .T Volitional collapse (loss of the will to live) in patients with burn injuries. Treatment strategy. .P JOURNAL ARTICLE. .W Volitional collapse, or loss of the will to live, remains one of the most vexing of the various system failures complicating serious illness or injury. It resembles, but is distinguishable from, major depression. Two features of volitional collapse may sometimes be turned to therapeutic advantage: it releases the patient from a struggle that may be dissipating already depleted energy reserves, and it transfers survival responsibility from one who has given up to others who have not. Preferred treatment involves carefully orchestrated initiatives from the patient's physician, closest friend, and spouse; their leverage derives from traditional sources, most importantly psychologic transference, bonding, and conjugal commitment. A burn unit provides an ideal environment in which to study the disorder and its response to treatment. .A Tempereau CE; Grossman AR; Brones MF. .I 201388 .U 90009194 .S J Clin Endocrinol Metab 9001; 69(5):1003-9 .M Adult; Binding Sites; Complement 3/*BI/SE; Electrophoresis, Polyacrylamide Gel; Endometriosis/*IM; Endometrium/*ME; Epithelium/ME; Female; Human; IgG/IM; Precipitin Tests; Spectrometry, Fluorescence; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tissue Culture. .T Production and secretion of complement component 3 by endometriotic tissue. .P JOURNAL ARTICLE. .W Many investigators have described a variety of immune phenomena associated with endometriosis. Among these are elevated titers of activated macrophages, monokines, and lymphokines in the peritoneal fluid of patients with endometriosis. In 1980, Weed and Arquembourg first described the deposition of complement component C3 in epithelial cells of endometrial glands in patients with endometriosis. In this study our objective was to examine the synthesis and secretion of proteins by endometriotic tissue. Tissues were incubated in Minimal Essential Medium without methionine containing 50 microCi/mL [35S]methionine for 12-16 h at 37 C in 5% CO2-95% air. Twenty thousand trichloroacetic acid-precipitable counts were placed on a 7.5% sodium dodecyl sulfate-polyacrylamide gel, and the radiolabeled proteins were detected by fluorography. We examined the radiolabeled secretory proteins obtained from 17 endometriotic implants and/or endometrioma cyst walls as well as 8 control tissues. A 180 kDa protein was produced in much greater quantities by endometriotic tissue than by control tissues. In the presence of reducing agent this protein dissociated into 113- and 69-kDa subunits. To identify and quantitate this protein we performed immunoprecipitations on the incubated medium using antihuman C3 immunoglobulin G. Up to 16% of the precipitable counts were recovered with this antibody from endometriotic tissue, while a maximum of only 4.6% was recovered from control tissue. In addition, we isolated and incubated the epithelial glandular cells, stromal cells, and remaining cells from two endometriomas. The great majority of the newly synthesized and secreted C3 was found in the glandular epithelial cell incubation. Up to 60% of the total precipitable counts were recovered from the glandular cells using this antibody. Only one protein was immunoprecipitated. The immunoprecipitated protein had a mol wt of 180 kDa under nonreducing conditions and dissociated into two subunits of 113 and 69 kDa in the presence of dithiothreitol. We conclude that the glandular epithelial cells found in endometriotic implants produce and secrete complement component, C3 which could be responsible for many of the immunological phenomena now well described in endometriosis. .A Isaacson KB; Coutifaris C; Garcia CR; Lyttle CR. .I 201389 .U 90009196 .S J Clin Endocrinol Metab 9001; 69(5):1019-23 .M Cells, Cultured; Comparative Study; Connective Tissue/DE/*ME; Dexamethasone/*PD; Eye/*ME; Fibroblasts/ME; Glycosaminoglycans/BI; Graves' Disease/ME; Human; Hyaluronic Acid/*BI; Skin/*ME; Support, U.S. Gov't, Non-P.H.S.; Triiodothyronine/*PD. .T Hormonal regulation of hyaluronate synthesis in cultured human fibroblasts: evidence for differences between retroocular and dermal fibroblasts. .P JOURNAL ARTICLE. .W Fibroblasts derived from retroocular connective tissue and skin were propagated in culture in an effort to identify structural and functional differences in connective tissue which might explain the apparent region-specific involvement in Graves' disease. Striking morphological differences existed between cultured cells from the two anatomical sites. Inhibition of glycosaminoglycan (GAG) accumulation by T3 and dexamethasone in these cultures was compared. Confluent cultures were labeled with [3H]acetate, and total [3H]GAG was quantitated. Fibroblasts from the skin responded to T3 (100 nmol/L) and dexamethasone (100 nmol/L) with 27% and 55% inhibition of [3H]GAG accumulation, respectively (n = 12). In contrast, retroocular fibroblasts responded with 12% and 8% inhibition (n = 6) to the two hormones. When cultures from abdominal skin and retroocular tissue were treated with n-butyrate (10 mM), a compound known to inhibit hyaluronate specifically, they responded similarly with 78% and 83% inhibition, respectively. A pulse-chase study was performed using fibroblasts from both sites, and no [3H]GAG degradation could be detected for the duration of the chase period (up to 72 h). These results suggest that retroocular fibroblasts, likely participants in the pathogenesis of Graves' ophthalmopathy, do not respond vigorously to T3 or glucocorticoids in terms of inhibition of [3H]GAG synthesis as do their dermal counterparts. .A Smith TJ; Bahn RS; Gorman CA. .I 201390 .U 90009197 .S J Clin Endocrinol Metab 9001; 69(5):1024-7 .M Age Factors; Aged; Bone and Bones/*ME; Bone Density/*DE; Calcium/BL; Comparative Study; Female; Human; Hydroxyproline/UR; Infusions, Intravenous; Menopause; Middle Age; Osteoporosis, Postmenopausal/DT/*ME; Parathyroid Hormones/*TU; Support, U.S. Gov't, P.H.S.. .T Bone responsiveness to parathyroid hormone in normal and osteoporotic postmenopausal women. .P JOURNAL ARTICLE. .W Increased bone loss in estrogen-deficient normal and osteoporotic postmenopausal women may be due mainly to increased sensitivity of bone-resorbing cells to circulating PTH, but this is supported only by indirect data. Therefore, we tested the responsiveness of bone to PTH directly by using a 3-day iv infusion of bovine PTH-(1-34) at 400 U/day in 9 normal premenopausal women, 10 normal postmenopausal women, and 12 osteoporotic postmenopausal women. Serum calcium and urinary hydroxyproline concentrations increased (P less than 0.001) over baseline values during infusion, but the mean increases in both variables did not differ among groups. The data do not support the hypothesis that estrogen deficiency increases the sensitivity of bone to PTH or that the sensitivity in osteoporotic women is greater than that in normal postmenopausal women. Within the constraints imposed by the method of testing, we conclude that the additional bone resorption induced by menopause and by osteoporosis may be due to mechanisms that are not due to enhanced responsiveness of bone to PTH. .A Tsai KS; Ebeling PR; Riggs BL. .I 201391 .U 90009198 .S J Clin Endocrinol Metab 9001; 69(5):1028-32 .M Adrenocorticotropic Hormone/*AD/PK; Adult; Aldosterone/*BL; Circadian Rhythm; Comparative Study; Drug Administration Schedule; Human; Hydrocortisone/BL; Infusions, Intravenous; Male; Support, U.S. Gov't, P.H.S.; Time Factors. .T Adrenocorticotropin stimulation of aldosterone: prolonged continuous versus pulsatile infusion. .P JOURNAL ARTICLE. .W Continuous iv administration of ACTH leads to a sustained stimulation of cortisol but a transient stimulation of aldosterone followed by a decline to prestimulation levels by 72 h. Since CRH and ACTH are released in a pulsatile pattern in man, this study sought to investigate whether pulsatile administration of alpha-cosyntropin-(1-24) would lead to the maintenance of aldosterone stimulation over time. Eight normal male subjects on a 10-meq sodium, 100-meq potassium diet received both a continuous and a pulsatile (0.33 U ACTH/pulse over 15 min, pulsed every 2 h) infusion of cosyntropin (4 U/24 h) for 48 h (n = 4) or 72 h (n = 4). Aldosterone and cortisol were sampled every 6 h, and PRA and angiotensin-II every 24 h. Continuous infusion led to a stimulation of aldosterone followed by a progressive decline to preinfusion levels by 72 h [preinfusion 29 +/- 5 ng/dL (810 +/- 139 pmol/L); 72 h, 38 +/- 10 ng/dL (1054 +/- 277 pmol/L); P = 0.40]. Pulsatile infusion led to a stimulation of aldosterone which was maintained up to 72 h [preinfusion 33 +/- 7 ng/dL (915 +/- 194 pmol/L); 72 h, 85 +/- 13 ng/dL (2358 +/- 361 pmol/L); P less than 0.05]. Regression analysis of aldosterone (y) over time (x) from the peak level at 18 h for the continuous infusion showed a significant negative relation (r = 0.63; P = 0.001), indicating a progressive decline in aldosterone. However, for the pulsatile infusion, there was no relation (r = 0.02; P = 0.85), indicating maintenance of aldosterone levels. There were no significant differences in sodium, potassium, PRA, angiotensin-II, or cortisol between infusions to explain these differences in aldosterone levels. Therefore, pulsatile infusion of cosyntropin maintains aldosterone secretion over time. .A Seely EW; Conlin PR; Brent GA; Dluhy RG. .I 201392 .U 90009201 .S J Clin Endocrinol Metab 9001; 69(5):1047-52 .M Adult; Androstenedione/*BI/BL; Dehydroepiandrosterone/*AA/AD/*BI/BL/PK; Dose-Response Relationship, Drug; Estrone/AD; Female; Follicular Phase; Human; Mathematics; Metabolic Clearance Rate; Radioimmunoassay; Stanolone/*BL; Support, U.S. Gov't, P.H.S.; Testosterone/*BI/BL. .T Metabolic clearance rate (MCR) of dehydroepiandrosterone sulfate (DS), its metabolism to dehydroepiandrosterone, androstenedione, testosterone, and dihydrotestosterone, and the effect of increased plasma DS concentration on DS MCR in normal women. .P JOURNAL ARTICLE. .W The combined infusion of [3H]dehydroepiandrosterone sulfate [( 3H]DS) and [14C]estrone (E1) for 6 h in four normal women in the follicular phase of the cycle demonstrated values of 13.77 +/- 0.27 L/day (mean +/- SE) for the DS MCR (MCRDS) and 1343 +/- 206 L/day for MCRE1. The fraction of DS metabolized to dehydroepiandrosterone (D), [rho]DS-D, was 0.285 +/- 0.044, and the fraction of D arising from DS (delta D) was 0.318 +/- 0.096, determined using isotopic techniques. Raising the plasma DS concentration by 8.6 micrograms/mL (23 mumol/L) by infusing DS iv increased the MCRDS to 24.49 L/day in the first subject, and raising the plasma DS by 11.40 +/- 0.33 micrograms/mL (30.94 +/- 0.90 mumol/L) in the next three subjects raised the MCRDS to 35.7 +/- 1.3 L/day (P less than 0.01) without changing the MCRE1. The increase in MCRDS produced by increasing plasma DS makes it difficult to accurately measure the MCRDS in effect at the subject's endogenous plasma DS concentration by infusion of nonisotopic DS. Determination of the fractions of D, androstenedione (delta delta 4A), and testosterone (T) arising from DS using the increase in the plasma concentrations of these steroids produced by infusion of nonisotopic DS gave the following estimates: delta D = 0.262 +/- 0.042, delta delta 4A = 0.089 +/- 0.046, and delta T = 0.273 +/- 0.14. .A Haning RV Jr; Chabot M; Flood CA; Hackett R; Longcope C. .I 201393 .U 90009204 .S J Clin Endocrinol Metab 9001; 69(5):1065-8 .M Adult; Amniotic Fluid/*ME; Circadian Rhythm; Female; Human; Labor/*; Melatonin/*ME/PH; Pregnancy; Radioimmunoassay; Time Factors. .T Serum and amniotic fluid melatonin during human labor. .P JOURNAL ARTICLE. .W The serum and amniotic fluid concentrations of melatonin (MT) were measured by RIA during human labor in different conditions related to the type of delivery and the time of the day of delivery. Serum MT concentrations displayed a normal diurnal rhythm, resembling that of nongravid women; the mean concentration [163.8 +/- 149.6 (+/- SD) pmol/L] at night was significantly (P less than 0.001) higher than that during the day (31.4 +/- 16.3 pmol/L). The amniotic fluid MT concentration, which showed a significant positive correlation to the serum MT concentration (r = 0.625; P less than 0.01), also showed an obvious diurnal rhythm; the mean MT concentration was significantly (P less than 0.01) higher during the night [99.3 +/- 59.3 (+/- SD) pmol/L] than during the day (58.9 +/- 33.5 pmol/L). Reverse phase high pressure liquid chromatography confirmed that the amniotic fluid MT immunoreactivity eluated as synthetic MT. During the night the mean amniotic fluid MT concentration [99.3 +/- 59.3 (+/- SD) pmol/L] was significantly (P less than 0.01) lower than that in serum (178.9 +/- 189.6 pmol/L). The progress of delivery, estimated by cervical dilatation, did not affect serum MT concentrations. Induction of delivery by amniotomy and/or oxytocin, and operative delivery by cesarean section had no effect on serum MT concentrations. Human MT secretion does not seem to be influenced by the physical stress of labor or endocrine changes associated with parturition. The single factor regulating MT secretion during human delivery appears to be the time of day. .A Kivela A; Kauppila A; Leppaluoto J; Vakkuri O. .I 201394 .U 90009205 .S J Clin Endocrinol Metab 9001; 69(5):1069-72 .M Antibodies, Monoclonal; Antibody Specificity; Antigenic Determinants/AN; Female; Human; Immunohistochemistry; Pituitary Gland, Anterior/*ME/UL; Placenta/CY/*ME/UL; Pregnancy; Somatotropin/GE/IM/*ME; Stains and Staining; Support, U.S. Gov't, P.H.S.. .T Immunocytochemical localization of the human growth hormone variant in the human placenta. .P JOURNAL ARTICLE. .W Two monoclonal antibodies (Mab 5B4 and K24) were used for the immunocytochemical localization of human GH (hGH) and human placental GH in the human pituitary and placenta. On the basis of prior selection by RIA, Mab 5B4 was known to be directed to the N-terminal of hGH and was able to detect both pituitary and placental hGH, since their primary amino acid sequences are identical in this domain. Mab K24 was directed to an epitope present in hGH, but not in placental hGH, and was able to detect pituitary hGH only; neither the 5B4 or K24 Mab detected human placental lactogen. Five placentas were studied from women at term after elective cesarean section without labor. The cells of the anterior pituitary gland and the syncytiotrophoblast of the placental villi were stained with Mab 5B4, whereas K24 only stained the pituitary cells; results consistent with the RIA screen. Mab 5B4 specifically stained two different cell types in the placental basal plate. Neither antiserum stained any cell in the amniotic or chorionic membranes or the adherent decidua. The results demonstrate that pituitary hGH and placental hGH are expressed uniquely in the pituitary and fetal placenta, respectively. In addition, the placental hGH gene is also expressed in the placental basal plate, a region of mixed fetal and maternal cells. .A Jara CS; Salud AT; Bryant-Greenwood GD; Pirens G; Hennen G; Frankenne F. .I 201395 .U 90009207 .S J Clin Endocrinol Metab 9001; 69(5):1078-81 .M Adrenal Cortex/*PP; Adrenal Gland Neoplasms/PP/RA/*SU; Adrenalectomy/*; Adult; Case Report; Female; Follow-Up Studies; Human; Neoplasms, Multiple Primary/*; Pheochromocytoma/PP/RA/*SU; Tomography, X-Ray Computed. .T Partial adrenalectomy for pheochromocytoma with maintenance of adrenocortical function. .P JOURNAL ARTICLE. .W A 30-yr-old woman with malignant hypertension was found to have biochemical evidence of pheochromocytoma. Bilateral adrenal tumors were demonstrated on computerized tomographic scanning and confirmed at the time of surgery. Complete removal of one adrenal gland with partial removal of the other adrenal gland resulted in normalization of her blood pressure and biochemical parameters (norepinephrine and epinephrine) with preservation of adrenocortical function. .A Birnbaum J; Giuliano A; Van Herle AJ. .I 201396 .U 90009208 .S J Clin Endocrinol Metab 9001; 69(5):1082-6 .M Adult; Aged; Female; Human; Hyperthyroidism/*PP/TH; Hypothyroidism/*PP/TH; Male; Middle Age; Muscles/*PP/RA; Muscular Atrophy/RA; Support, Non-U.S. Gov't; Thigh/*; Tomography, X-Ray Computed. .T Effect of thyroid dysfunction on thigh muscle efficiency. .P JOURNAL ARTICLE. .W To establish whether muscle weakness in thyroid dysfunction can be attributed solely to muscle atrophy (i.e. reduction in the total muscle cross-section) or whether the intrinsic contractile strength of the muscle is reduced per unit cross-sectional area, the ratio between thigh muscle strength and thigh muscle area was determined before and after treatment of hyper- and hypothyroidism. Midthigh muscle areas, assessed by computer tomography, increased in all seven hyperthyroid and decreased in three of four hypothyroid patients investigated after treatment of the thyroid disease. Peak torque and total work output, assessed by an isokinetic dynamometer (Cybex II), increased in both groups of patients. The muscle efficiency (total work output per cm2 muscle) increased in all patients after therapy [mean +/- SD values before vs. after therapy in hyperthyroid patients, 17.6 +/- 5.3 vs. 30.5 +/- 3.7 joules (J)/cm2 (P less than 0.001); in hypothyroid patients, 12.8 +/- 6.1 J/cm2 vs. 25.8 +/- 8.6 J/cm2 (P less than 0.05)]. Thus, the present study demonstrates that patients with thyroid dysfunction have altered muscle mass and diminished muscle efficiency. .A Zurcher RM; Horber FF; Grunig BE; Frey FJ. .I 201397 .U 90009210 .S J Clin Endocrinol Metab 9001; 69(5):925-8 .M Follow-Up Studies; Human; Neoplasms, Radiation-Induced/*DI/ET/SU; Radiotherapy/AE; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Thyroid Gland/*RE; Thyroid Neoplasms/*DI/ET/SU. .T Clinical review 2: Diagnostic approach and management of patients exposed to irradiation to the thyroid. .P JOURNAL ARTICLE. .A DeGroot LJ. .I 201398 .U 90009211 .S J Clin Endocrinol Metab 9001; 69(5):929-31 .M Absorptiometry, Photon; Bone Density; Female; Human; Osteoporosis/*DT; Sodium Fluoride/AE/*TU; Spine/AN/DE. .T Fluoride and the therapy of osteoporosis [editorial] .P EDITORIAL. .A Brown EM. .I 201399 .U 90009212 .S J Clin Endocrinol Metab 9001; 69(5):932-8 .M Absorptiometry, Photon; Aged; Bone Density/*; Calcium, Dietary/TU; Female; Human; Middle Age; Osteoporosis, Postmenopausal/*DT/ME; Prospective Studies; Sodium Fluoride/AE/*TU; Spine/*DE/ME; Statistics; Support, Non-U.S. Gov't; Time Factors. .T The response of vertebral bone mineral density during the treatment of osteoporosis with sodium fluoride. .P JOURNAL ARTICLE. .W Forty-eight female patients with postmenopausal osteoporotic vertebral compression fractures were treated with sodium fluoride and calcium supplements; their response to treatment was documented by sequential measurements of vertebral and forearm bone mineral density (BMD). During treatment 25 patients developed significant side-effects due to fluoride, and ultimately, 18 patients (37%) were intolerant of the drug after 17.3 +/- 7.3 (+/- SD) months. The remaining patients were followed for 29.4 +/- 9.6 months. By linear regression analysis, 69% of patients had a positive slope of vertebral BMD vs. time of greater than 0.0017 g/cm2.month (range, 0.0017-0.01) and were classified as treatment responders. The increment in vertebral BMD above the baseline value over time was described by the relationship delta BMD (g/cm2.month) = 0.042 + 0.0053 x months, equivalent to a rate of 8.4%/yr. Because the rates of increasing BMD were very variable, it was difficult to determine in individual patients the point at which a positive response to treatment had occurred; by calculating the 95% confidence target BMD by which the BMD must rise above the initial value before discounting the imprecision of the measurements (0.062 g/cm2), only 70% of responders were identified by 12 months. The total cumulative dose of sodium fluoride (31.3 +/- 16.4 g) was significantly higher in patients classified as responders than in the nonresponders (20.6 +/- 13.4 g; P less than 0.05), probably because of differences in side-effects between the two groups. In contrast, forearm BMD fell significantly in the responders by an average of 7.7%/yr, suggesting the possibility of a preferential improvement in axial bone density at the expense of cortical bone. Thus, the majority of patients treated with fluoride respond with increasing vertebral BMD, but it may take 12-24 months to identify these individually. .A Hodsman AB; Drost DJ. .I 201400 .U 90009213 .S J Clin Endocrinol Metab 9001; 69(5):939-45 .M Adult; Autoantibodies/BI; B-Lymphocytes/*IM; Cell Cycle; Cells, Cultured; Female; Graves' Disease/*IM; Human; IgG/BI; Male; Middle Age; Phenotype; Thyroid Gland/*IM. .T Abnormal B lymphocyte function in thyroid glands from patients with Graves' disease. .P JOURNAL ARTICLE. .W Thyroid-infiltrating B lymphocytes from patients with Graves' disease were investigated in regard to their phenotypic profiles, cell size, cell cycle status, proliferative response to Staphylococcus aureus Cowan 1 (SAC), and spontaneous production of immunoglobulin G (IgG) and antithyroidal autoantibodies. Thyroid tissues and peripheral blood were obtained at the time of subtotal thyroidectomy of 27 Graves' patients who had been treated with thionamide drugs and iodide before operation. Two intrathyroidal mononuclear cell populations were obtained from these thyroid tissues. One cell population was isolated from the supernatants after mechanical disaggregation of the tissues and was defined as TG-1 cells. Another cell population, defined as TG-2 cells, was isolated from the supernatants of overnight cultures of the thyroid debris after enzymatic digestion. The percentages of B lymphocytes bearing activated markers and plasma cells (CD20+CD21-, IgM+IgD-, CD20+ transferrin receptor+, PCA-1+) were significantly higher in the TG-1 and TG-2 cell populations than in peripheral blood from Graves' disease patients and normal subjects. These phenotypic changes were accompanied by increased thyroid gland B lymphocyte cell size from patients with Graves' disease. The proliferative response of B lymphocytes to SAC was markedly lower in TG-1 and TG-2 cell populations than in peripheral blood cells from Graves' disease patients and normal subjects. B lymphocytes isolated from thyroid glands secreted significantly more IgG and antithyroidal autoantibodies than those from peripheral blood. Based on the findings of abnormalities in thyroid-infiltrating B lymphocytes, we suggest that activated B lymphocytes may induce the excessive production of antithyroidal autoantibodies in thyroid glands from patients with Graves' disease. .A Ueki Y; Eguchi K; Otsubo T; Kawabe Y; Shimomura C; Tezuka H; Nakao H; Kawakami A; Migita K; Ishikawa; et al. .I 201401 .U 90009215 .S J Clin Endocrinol Metab 9001; 69(5):950-5 .M Adenoma/CO; Adult; Chromogranins/*BL; Female; Human; Hyperparathyroidism/*BL/ET/SU; Hyperplasia/CO/GE; Male; Middle Age; Neoplasms, Multiple Endocrine/*BL/CO; Nerve Tissue Proteins/*BL; Parathyroid Diseases/CO; Parathyroid Glands/SU; Parathyroid Neoplasms/CO; Retrospective Studies; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Plasma chromogranin-A in primary hyperparathyroidism. .P JOURNAL ARTICLE. .W We sought an explanation for prior findings of high plasma chromogranin-A (Chr-A) in primary hyperparathyroidism. Chr-A was measured in plasma samples from 55 controls and 73 patients with primary hyperparathyroidism caused by adenoma (n = 14), sporadic or familial hyperplasia (n = 10), or familial multiple endocrine neoplasia type 1 (FMEN1; n = 49). Serum or plasma samples were also tested for calcium, PTH, gastrin, pancreatic polypeptide, CG alpha, and PRL. Plasma Chr-A was 34 +/- 10 in parathyroid adenoma, 55 +/- 33 in parathyroid hyperplasia without FMEN1, 63 +/- 88 in FMEN1, and 25 +/- 8 in controls (mean +/- SD; nanograms per ml; FMEN1 or parathyroid hyperplasia vs. control, P less than 0.05). Plasma Chr-A did not correlate with other hormonal variables in controls. Plasma Chr-A correlated with log serum gastrin (r = 0.43; P = 0.003) and plasma PTH (r = 0.52; P less than 0.05) only in FMEN1. In FMEN1, plasma Chr-A was highest in subjects with Zollinger-Ellison syndrome (ZES, 120 +/- 127; no ZES, 30 +/- 33 (P less than 0.0001). Parathyroidectomy did not decrease plasma Chr-A in patients with parathyroid adenoma or parathyroid hyperplasia. For FMEN1 patients with available pre- and postparathyroidectomy samples, Chr-A decreased postoperatively in four of five patients with ZES compared to none of six patients without ZES (P less than 0.05). Elevated plasma Chr-A is not a general feature of primary hyperparathyroidism. Elevated plasma Chr-A in primary hyperparathyroidism was restricted principally to patients who also had ZES. Primary hyperparathyroidism may influence the level of Chr-A by an effect of hypercalcemia or elevated PTH on Chr-A secretion from pancreatic islet tissue. .A Nanes MS; O'Connor DT; Marx SJ. .I 201402 .U 90009216 .S J Clin Endocrinol Metab 9001; 69(5):956-62 .M Animal; Dose-Response Relationship, Drug; Female; Fetal Blood/ME; Infusions, Intravenous; Macaca mulatta; Maternal-Fetal Exchange; Menstrual Cycle/DE; Ovulation/DE; Pituitary Gland/DE/PH; Pregnancy; Prolactin/*BL/SE; Relaxin/AD/*PD; Somatotropin/*BL/SE; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T The effect of relaxin infusion on prolactin and growth hormone secretion in monkeys. .P JOURNAL ARTICLE. .W To test the hypothesis that relaxin may affect pituitary hormone secretion, synthetic human relaxin was infused into cycling and pregnant rhesus monkeys. Doses ranging from 0.154-1540 ng/kg.min were calculated to achieve circulating relaxin concentrations of 1 pM to 10 nM. Low (0.154 and 1.54 ng/kg.min), intermediate (15.4 and 154 ng/kg.min), and high (1540 ng/kg.min) doses of relaxin were infused for 15 min each hour into ovulating monkeys at the midluteal phase of the menstrual cycle in two separate experiments. Serum GH and PRL were measured by RIA, and serum relaxin was determined by enzyme-linked immunosorbent assay. Relaxin was undetectable in peripheral plasma during the control saline infusion and during infusion of the lowest dose of relaxin. Serum relaxin levels reached 0.011, 0.119, 0.965, and 13.0 nM with 1.54, 15.4, 154, and 1540 ng/kg.min, respectively. Serum GH was significantly elevated over basal levels upon infusion of relaxin from 1.54-1540 ng/kg.min; however, a plateau was observed with the intermediate doses, and a decrease in the magnitude of the response was observed at the highest dose. Serum PRL increased over basal levels with 15.4 and 154 ng/kg.min, but there was no difference in the magnitude of the increase between these doses. PRL levels during infusion of the highest dose of relaxin were similar to control levels. These data suggest that relaxin can stimulate secretion of GH and PRL in cycling monkeys within a defined dose range, but that a decrease in pituitary responsiveness occurs at higher doses. One high dose of relaxin (2600 ng/kg.min) was infused for 1 h into the maternal and then the fetal circulations of chronically catheterized and tethered pregnant monkeys between 120-140 days gestation. Upon infusion of relaxin into the maternal circulation, there was a significant elevation of PRL in the mother but not the fetus. Upon infusion of relaxin into the fetus, there was no consistent change in PRL secretion in either the mother or the fetus. In conclusion, relaxin may have a heretofore undescribed role in pituitary physiology during the menstrual cycle and in pregnancy. .A Bethea CL; Cronin MJ; Haluska GJ; Novy MJ. .I 201403 .U 90009219 .S J Clin Endocrinol Metab 9001; 69(5):978-84 .M Adult; Africa; B-Lymphocytes/DE/*ME/MI; Cell Transformation, Viral; Cells, Cultured; Dwarfism/*ME; Epstein-Barr Virus; Female; Human; Insulin-Like Growth Factor I/*ME; Insulin-Like Growth Factor II/ME; Lymphocyte Transformation/*DE; Male; Somatomedins/*ME; Somatotropin/PD; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Viral Proteins/PD. .T Insulin-like growth factor secretion by human B-lymphocytes: a comparison of cells from normal and pygmy subjects. .P JOURNAL ARTICLE. .W Freshly isolated human B-lymphocytes from eight subjects and Epstein-Barr virus-transformed human B-lymphocytes from seven subjects were examined for their capacity to secrete insulin-like growth factor-I (IGF-I) and IGF-II and for their capacity to respond to human GH. Similar studies were conducted with Epstein-Barr virus-transformed lymphocytes collected from six African pygmies. When transformed B-lymphocytes from normal stature subjects were cultured for 3 weeks in RPMI-1640 medium (6 x 10(3) cells/75-cm2 flask at seeding), significant amounts of IGF-I, but no IGF-II, were produced. GH (150 ng/mL) significantly increased for control cells the amount of IGF-I produced at each sampling interval compared to that by unstimulated cultures (P less than 0.05 at 1 week; P = 0.005 at 3 weeks). At 3 weeks, cell counts of cultures compared were 4.13 +/- 0.39 X 10(6)/mL for unstimulated cells and 4.23 +/- 0.87 X 10(6)/mL for GH-stimulated cells. IGF-I production at this time interval by unstimulated cells was 2.8 +/- 2.3 ng/mL, and that by GH-stimulated cells was 12.3 +/- 2.5 ng/mL (P = 0.005). Cell multiplication rates of control cultures were increased in 1 week by GH stimulation [GH stimulated, [16.7 +/- 22.0 X 10(4) cells, unstimulated, 5.73 +/- 4.1 X 10(4) cells; (mean +/- SD); n = 14; P less than 0.01]. Similar results occurred with GH studied at a lower concentration of 10 ng/mL for 3 weeks. Freshly isolated B-lymphocytes did not secrete IGF-I and II after 5 days of culture with GH. Cultures established from cells derived from pygmies produced significantly less IGF-I (4.24 +/- 2.62 ng/mL) when stimulated with 150 ng/mL GH than cultures of cells from normal stature subjects (12.3 +/- 2.5 ng/mL; 0.005 less than P less than 0.01). The cultures compared had a similar cell density. A similar significant difference in IGF-I secretion occurred between cultures of pygmy and control cells stimulated with 10 ng/mL GH. These data are consistent with previous in vivo studies in which pygmies failed to increase IGF-I and exhibit metabolic responses to exogenous GH. .A Merimee TJ; Grant MB; Broder CM; Cavalli-Sforza LL. .I 201404 .U 90009220 .S J Clin Endocrinol Metab 9001; 69(5):985-95 .M Adult; Aged; Aged, 80 and over; Binding Sites; Chromatography, Affinity; Concanavalin A/*; Female; Glycopeptides/BL/IP; Human; Hydrolysis; Hypothyroidism/*BL; Lectins/*; Legumes; Male; Middle Age; Molecular Structure; Neuraminidase; Ricin/*; Sialic Acids/BL; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Thyrotropin/*BL/IP. .T Concanavalin-A, lentil, and ricin lectin affinity binding characteristics of human thyrotropin: differences in the sialylation of thyrotropin in sera of euthyroid, primary, and central hypothyroid patients. .P JOURNAL ARTICLE. .W TSH from human serum was separated into classes by serial lectin affinity chromatography using Concanavalin-A (ConA), lentil, and ricin lectins. TSH from 10 euthyroid subjects, 40 patients with primary hypothyroidism, and 1 patient with central hypothyroidism was studied. The patterns of ConA and lentil affinity binding were similar for diverse patients; forms of TSH that bound firmly to ConA also tended to bind firmly to lentil. Differences in TSH-ricin binding suggested that there were differences in the sialylation of TSH in sera of euthyroid, primary, and central hypothyroidism patients. For euthyroid subjects, 16.1 +/- 5.4% (mean +/- SD) of the TSH bound to ricin, while after neuraminidase treatment, 38.4 +/- 5.4% bound. For patients with primary hypothyroidism, 23.5 +/- 6.0% of the TSH bound to the ricin, while after neuraminidase treatment, 65.7 +/- 8.8% bound. The increase in ricin binding induced by neuraminidase treatment was significantly higher for TSH from patients with primary hypothyroidism than in that from euthyroid subjects (42.3 +/- 7.6% vs. 22.3 +/- 4.4%; P less than 0.01) and was greater for long term than for short term hypothyroid patients (49.5 +/- 5.0% vs. 36.5 +/- 6.5%; P less than 0.01). While 30% of native TSH from the serum of the patient with central hypothyroidism bound to ricin, the amount bound increased only 17.6% after neuraminidase treatment. McKenzie bioassay of pituitary-derived TSH that was similarly fractionated using ricin failed to show detectable differences in bioactivity among the lectin column fractions. Thus, 1) circulating human TSH can be consistently separated into discrete classes using serial lectin affinity chromatography; 2) there is relatively more core fucosylation of the less processed high mannose and hybrid forms of TSH and less core fucosylation of more processed complex forms; 3) ConA and lentil binding of TSH in primary and central hypothyroidism is similar to that in the euthyroid state; 4) patients with primary hypothyroidism have more sialylated TSH than a patient with central hypothyroidism or euthyroid subjects; and 5) the degree of TSH sialylation increases with prolonged primary hypothyroidism. .A Miura Y; Perkel VS; Papenberg KA; Johnson MJ; Magner JA. .I 201405 .U 90009294 .S J Clin Invest 9001; 84(4):1056-62 .M Adult; Carbohydrates/ME; Comparative Study; Diarrhea/ET/*PP; Disaccharides/*AE; Electrolytes/AN; Feces/AN; Human; Intestinal Absorption/DE; Lactulose/*AE; Male; Osmolar Concentration; Polyethylene Glycols/*AE; Reference Values; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Water/AN. .T Studies of osmotic diarrhea induced in normal subjects by ingestion of polyethylene glycol and lactulose. .P JOURNAL ARTICLE. .W The purpose of these studies was to gain insight into the pathophysiology of pure osmotic diarrhea and the osmotic diarrhea caused by carbohydrate malabsorption. Diarrhea was induced in normal volunteers by ingestion of polyethylene glycol (PEG), which is nonabsorbable, not metabolized by colonic bacteria, and carries no electrical charge. In PEG-induced diarrhea, (a) stool weight was directly correlated with the total mass of PEG ingested; (b) PEG contributed 40-60% of the osmolality of the fecal fluid, the remainder being contributed by other solutes either of dietary, endogenous, or bacterial origin; and (c) fecal sodium, potassium, and chloride were avidly conserved by the intestine, in spite of stool water losses exceeding 1,200 g/d. Diarrhea was also induced in normal subjects by ingestion of lactulose, a disaccharide that is not absorbed by the small intestine but is metabolized by colonic bacteria. In lactulose-induced diarrhea, (a) a maximum of approximate 80 g/d of lactulose was metabolized by colonic bacteria to noncarbohydrate moieties such as organic acids; (b) the organic acids were partially absorbed in the colon; (c) unabsorbed organic acids obligated the accumulation of inorganic cations (Na greater than Ca greater than K greater than Mg) in the diarrheal fluid; (d) diarrhea associated with low doses of lactulose was mainly due to unabsorbed organic acids and associated cations, whereas with larger doses of lactulose unmetabolized carbohydrates also played a major role; and (e) the net effect of bacterial metabolism of lactulose and partial absorption of organic acids on stool water output was done dependent. With low or moderate doses of lactulose, stool water losses were reduced by as much as 600 g/d (compared with equimolar osmotic loads of PEG); with large dose, the increment in osmotically active solutes within the lumen exceeded the increment of the ingested osmotic load, and the severity of diarrhea was augmented. .A Hammer HF; Santa Ana CA; Schiller LR; Fordtran JS. .I 201406 .U 90009295 .S J Clin Invest 9001; 84(4):1063-9 .M Adolescence; Adult; Alprostadil/*TU; Aspartate Aminotransferase/BL; Bilirubin/BL; Blood Coagulation/DE; Child; Dinoprostone/TU; Female; Hepatitis, Viral, Human/BL/*DT; Human; Liver/DE/PA/PP; Male; Middle Age; Support, Non-U.S. Gov't. .T Biochemical and clinical response of fulminant viral hepatitis to administration of prostaglandin E. A preliminary report. .P JOURNAL ARTICLE. .W The effect of PG on patients with fulminant and subfulminant viral hepatitis (FHF) was studied. 17 patients presented with FHF secondary to hepatitis A (n = 3), hepatitis B (n = 6), and non-A, non-B (NANB) hepatitis (n = 8). 14 of the 17 patients had stage III or IV hepatic encephalopathy (HE). At presentation the mean aspartate transaminase (AST) was 1,844 +/- 1,246 U/liter, bilirubin 232 +/- 135 mumol/liter, prothrombin time (PT) 34 +/- 18, partial thromboplastin time (PTT) 73 +/- 26 s, and coagulation Factors V and VII 8 +/- 4 and 9 +/- 5%, respectively. Intravenous PGE1 was initiated 24-48 h later after a rise in AST (2,195 +/- 1,810), bilirubin (341 +/- 148), PT (36 +/- 15), and PTT (75 +/- 18). 12 of 17 responded rapidly with a decrease in AST from 1,540 +/- 833 to 188 +/- 324 U/liter. Improvement in hepatic synthetic function was indicated by a decrease in PT from 27 +/- 7 to 12 +/- 1 s and PTT from 61 +/- 10 to 31 +/- 2 s, and an increase in Factor V from 9 +/- 4 to 69 +/- 18% and Factor VII from 11 +/- 5 to 71 +/- 20%. Five responders with NANB hepatitis relapsed upon discontinuation of therapy, with recurrence of HE and increases in AST and PT, and improvement was observed upon retreatment. After 4 wk of intravenous therapy oral PGE2 was substituted. Two patients with NANB hepatitis recovered completely and remained in remission 6 and 12 mo after cessation of therapy. Two additional patients continued in remission after 2 and 6 mo of PGE2. No relapses were seen in the patients with hepatitis A virus and hepatitis B virus infection. Liver biopsies in all 12 surviving patients returned to normal. In the five nonresponders an improvement in hepatic function was indicated by a fall in AST (3,767 +/- 2,611 to 2,142 +/- 2,040 U/liter), PT (52 +/- 25 to 33 +/- 18 s), and PTT (103 +/- 29 to 77 +/- 44 s), but all deteriorated and died of cerebral edema (n = 3) or underwent liver transplantation (n = 2). These results suggest efficacy of PGE for FHF, and further investigation is warranted. .A Sinclair SB; Greig PD; Blendis LM; Abecassis M; Roberts EA; Phillips MJ; Cameron R; Levy GA. .I 201407 .U 90009296 .S J Clin Invest 9001; 84(4):1070-5 .M Adult; Aged; Antibodies, Viral/AN/*IM; Antibody Formation; Chromatography, High Pressure Liquid; Enzyme-Linked Immunosorbent Assay; Female; Glomerulonephritis, IGA/*IM; Human; IgA/AN; Immunoglobulin Isotypes/*AN; Influenza/*IM/PC; Influenza Vaccine/*TU; Male; Middle Age; Support, Non-U.S. Gov't. .T Humoral immune response to influenza vaccination in patients with primary immunoglobulin A nephropathy. An analysis of isotype distribution and size of the influenza-specific antibodies. .P JOURNAL ARTICLE. .W Primary IgA nephropathy (IgAN) is characterized by mesangial deposits of IgA1, increased serum IgA1 levels, and circulating immune complexes containing predominantly IgA1. It has previously been found that patients with IgAN have a higher than normal IgA response to vaccination, but the IgA subclasses have not been studied. To investigate whether the IgA hyperresponsiveness is limited to the subclass IgA1, which is involved in the pathogenesis of IgAN, we compared the immune responses of 18 patients with 22 healthy controls after intramuscular vaccination with inactivated influenza virus. Antibody titers were significantly higher (P less than 0.0001) for the IgA1 subclass in patients versus controls, but not for the other isotypes. A substantial portion of the IgA and IgA1 antiinfluenza immune response comprised polymers in both patients and controls. There was no preferential response of polymers in patients. Patients produced significantly more monomeric IgA1 antibodies than controls. These results show that patients with IgAN have a hyperresponsiveness limited to the subclass IgA1 and mainly expressed by an excess of monomers. .A van den Wall Bake AW; Beyer WE; Evers-Schouten JH; Hermans J; Daha MR; Masurel N; van Es LA. .I 201408 .U 90009298 .S J Clin Invest 9001; 84(4):1086-95 .M Adult; Animal; Aorta/ME; Apolipoproteins B/IM; Arteriosclerosis/*ME; Atherosclerosis/*ME; Blotting, Western; Electrophoresis, Polyacrylamide Gel; Human; Lipoproteins, LDL/*ME; Macrophages/ME; Male; Mice; Middle Age; Oxidation-Reduction; Rabbits; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man. .P JOURNAL ARTICLE. .W Three lines of evidence are presented that low density lipoproteins gently extracted from human and rabbit atherosclerotic lesions (lesion LDL) greatly resembles LDL that has been oxidatively modified in vitro. First, lesion LDL showed many of the physical and chemical properties of oxidized LDL, properties that differ from those of plasma LDL: higher electrophoretic mobility, a higher density, higher free cholesterol content, and a higher proportion of sphingomyelin and lysophosphatidylcholine in the phospholipid fraction. A number of lower molecular weight fragments of apo B were found in lesion LDL, similar to in vitro oxidized LDL. Second, both the intact apo B and some of the apo B fragments of lesion LDL reacted in Western blots with antisera that recognize malondialdehyde-conjugated lysine and 4-hydroxynonenal lysine adducts, both of which are found in oxidized LDL; plasma LDL and LDL from normal human intima showed no such reactivity. Third, lesion LDL shared biological properties with oxidized LDL: compared with plasma LDL, lesion LDL produced much greater stimulation of cholesterol esterification and was degraded more rapidly by macrophages. Degradation of radiolabeled lesion LDL was competitively inhibited by unlabeled lesion LDL, by LDL oxidized with copper, by polyinosinic acid and by malondialdehyde-LDL, but not by native LDL, indicating uptake by the scavenger receptor(s). Finally, lesion LDL (but not normal intimal LDL or plasma LDL) was chemotactic for monocytes, as is oxidized LDL. These studies provide strong evidence that atherosclerotic lesions, both in man and in rabbit, contain oxidatively modified LDL. .A Yla-Herttuala S; Palinski W; Rosenfeld ME; Parthasarathy S; Carew TE; Butler S; Witztum JL; Steinberg D. .I 201409 .U 90009299 .S J Clin Invest 9001; 84(4):1096-104 .M Amides/ME; Antithrombin III/ME; Blood Platelets/ME; Chondroitinases/ME; Electrophoresis, Polyacrylamide Gel; Extracellular Matrix/*ME; Glycosaminoglycans/ME; Human; Hydrolysis; Polysaccharide-Lyases/ME; Serotonin/ME; Substrate Specificity; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Thrombin/AI/*ME. .T Binding of thrombin to subendothelial extracellular matrix. Protection and expression of functional properties. .P JOURNAL ARTICLE. .W We have analyzed the binding of thrombin, a serine protease with central roles in hemostasis, to the subendothelial extracellular matrix (ECM) produced by cultured endothelial cells. This substrate provides a thrombogenic surface where hemostasis is initiated. Binding was saturable and equilibrium was achieved after 3 h incubation with 125I-alpha-thrombin. Scatchard analysis of thrombin binding revealed the presence of 5.1 X 10(9) binding sites per squared millimeter ECM, with an apparent Kd of 13 nM. The catalytically blocked enzyme, diisofluorophosphate (DIP)-alpha-thrombin competed efficiently with 125I-alpha-thrombin, indicating that the binding was independent of its catalytic site. Moreover, high concentrations of the synthetic tetradecapeptide, representing residues 367-380 of thrombin B chain (the macrophage mitogenic domain of thrombin), competed with thrombin binding to ECM, indicating that the binding site may reside in the vicinity of "loop B" region. Thrombin binds to dermatan sulfate in the ECM, as demonstrated by the inhibition of 125I-alpha-thrombin binding to ECM pretreated with chondroitinase ABC, but not with heparitinase or chondroitinase AC. This stands in contrast to 125I-FGF (fibroblast growth factor) binding to ECM, which was inhibited by heparitinase but not by chondroitinase ABC, ECM-bound thrombin exhibits an exposed proteolytic site as monitored by the Chromozyme TH assay and by its ability to convert fibrinogen to a fibrin clot and to induce platelet activation as indicated by 14C-serotonin release. ECM-bound thrombin failed to form a complex with its major circulating inhibitor-antithrombin III (AT III), compared with rapid complex formation with soluble thrombin. We propose that thrombin binds to subendothelial ECM where it remains functionally active, localized, and protected from inactivation by circulating inhibitors. .A Bar-Shavit R; Eldor A; Vlodavsky I. .I 201410 .U 90009300 .S J Clin Invest 9001; 84(4):1105-13 .M Adult; Amino Acid Sequence; Amino Acids/AN; Bombesin/*AN; Bronchoalveolar Lavage Fluid/*AN; Chromatography, High Pressure Liquid; Female; Human; Immunohistochemistry; Male; Middle Age; Molecular Sequence Data; Neuropeptides/*AN; Respiratory System/*ME; Smoking/*ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Tobacco/*. .T Increased levels of bombesin-like peptides in the lower respiratory tract of asymptomatic cigarette smokers. .P JOURNAL ARTICLE. .W Bombesin-related peptides are growth factors for a variety of cells, including normal human bronchial epithelial cells. An ELISA for bombesin-like peptides (BLP) has been devised using the MAb BBC353, which is specific for the biologically active carboxy-terminal fragment shared by all known BLP. Using this ELISA, we measured bronchoalveolar lavage (BAL) fluid levels of BLP in normal cigarette smokers (n = 15) and normal nonsmokers (n = 18). Smokers' BAL fluid contained increased levels of BLP, whether expressed in terms of BAL fluid volume (P = 0.0001) or protein content (P less than 0.05). BLP levels did not correlate with any cellular constituent in the BAL fluid but immunostaining of lung tissue with BBC353 revealed an intense specific staining of neuroendocrine cells, implying these as a potential source. Two peaks of bombesin-like immunoreactivity were purified using sequential reverse phase and gel filtration HPLC. Both BLP have apparent molecular weights similar to gastrin-releasing peptide on gel filtration HPLC analysis. However, the amino acid composition of these BLP is different from that of gastrin-releasing peptide or neuromedin B, the only known mammalian forms of BLP, suggesting either incomplete purification or novel peptides. Sequence analysis could not be performed due to blocking groups at the amino terminus of these peptides. Our data demonstrate that cigarette smoking is associated with increased levels of pulmonary BLP and imply a potential role for these neuropeptides in the lung's response to tobacco smoke. .A Aguayo SM; Kane MA; King TE Jr; Schwarz MI; Grauer L; Miller YE. .I 201411 .U 90009301 .S J Clin Invest 9001; 84(4):1114-23 .M Acquired Immunodeficiency Syndrome/CO/IM; Acute Disease; Adult; Antibodies, Viral/AN/*IM; Antibody Formation; Blotting, Western; Child, Preschool; Human; IgG/AN; IgM/AN; Immunity, Cellular; Leukemia, Lymphocytic, Acute, L1/CO/IM; Male; Parvoviridae/*IM/IP/UL; Parvovirus Infections/CO/*IM; Radioimmunoassay. .T Immune response to B19 parvovirus and an antibody defect in persistent viral infection. .P JOURNAL ARTICLE. .W B19 parvovirus has been shown to persist in some immunocompromised patients, and treatment with specific antibodies can lead to decreased quantities of circulating virus and hematologic improvement. A defective immune response to B19 parvovirus in these patients was shown by comparison of results using a capture RIA and immunoblotting. In normal individuals, examination of paired sera showed that the dominant humoral immune response during early convalescence was to the virus major capsid protein (58 kD) and during late convalescence to the minor capsid species (83 kD). In patients with persistent parvovirus infection, variable titers against intact particles were detected by RIA, but the sera from these patients had minimal or no IgG to capsid proteins determined by Western analysis. Competition experiments suggested that this discrepancy was not explicable on the basis of immune complex formation alone and that these patients may have a qualitative abnormality in antibody binding to virus. In neutralization experiments, in which erythroid colony formation in vitro was used as an assay of parvovirus activity, sera from patients with poor reactivity on immunoblotting were also inadequate in inhibiting viral infectivity. A cellular response to purified B19 parvovirus could not be demonstrated using proliferation assays and PBMC from individuals with serologic evidence of exposure to virus. These results suggest that production of neutralizing antibody to capsid protein plays a major role in limiting parvovirus infection in man. .A Kurtzman GJ; Cohen BJ; Field AM; Oseas R; Blaese RM; Young NS. .I 201412 .U 90009303 .S J Clin Invest 9001; 84(4):1130-3 .M Adrenal Glands/EN; Animal; Catecholamines/BL/UR; Denervation; Epinephrine/*BI/BL/UR; Kidney/IR/*ME; Male; Methyltransferases/ME; Phenethanolamine N-Methyltransferase/AI/ME; Rats; Rats, Inbred Strains; Support, U.S. Gov't, P.H.S.. .T Rat renal epinephrine synthesis. .P JOURNAL ARTICLE. .W Rats that underwent adrenal demedullation had a 93% decrease in plasma epinephrine (E) levels, but did not decrease their renal E. Even further treatment with 6-hydroxydopamine and reserpine failed to lower renal E levels. Similarly, urine E levels failed to decrease after adrenal demedullation and renal denervation. There is a renal E-synthesizing enzyme that differs from adrenal phenylethanolamine-N-methyltransferase (PNMT) in that it is only weakly inhibited by SKF 29661 and can synthesize epinine from dopamine, while adrenal PNMT does so poorly. When an adrenalectomized rat received intravenous [3H]methionine, its urine contained radioactivity that appeared to be [3H]E, with small amounts of [3H]epinine. However, after [3H]methionine was infused in the renal artery, the major product in urine appeared to be [3H]epinine, with a small amount of [3H]E. Adrenal demedullation induced renal E synthesis, but denervation returned the rate of renal E synthesis to control values. The combination of adrenal demedullation, 6-hydroxydopamine, and reserpine treatments increased renal E-forming activity to 350% of control. We conclude that appreciable portions of renal and urinary E are synthesized in the kidney by an enzyme distinct from PNMT. The enzyme is induced by some treatments that lower E and NE levels. .A Ziegler MG; Kennedy B; Elayan H. .I 201413 .U 90009304 .S J Clin Invest 9001; 84(4):1134-44 .M Animal; Arteries/*PP; Blood Platelets/*; Disease Models, Animal; Support, U.S. Gov't, P.H.S.; Swine; Thrombosis/*PP. .T Mechanisms of arterial thrombosis in nonparallel streamlines: platelet thrombi grow on the apex of stenotic severely injured vessel wall. Experimental study in the pig model. .P JOURNAL ARTICLE. .W The role of thrombosis in various acute coronary syndromes has been established. However, the basic mechanism by which plaque rupture leads to a growing thrombus in the vicinity of stenotic lesions is not well understood. Using a characterized flow chamber in a rheologically controlled system, we have mimicked stenotic vessels and studied for the first time cell-vessel wall interaction in nonparallel streamlines. Stenoses ranging from 0 to 80% were produced with stripped tunica media to mimic severe vessel wall damage, and perfused with heparinized flowing blood. This perfusion device was placed within an extracorporeal system in swine, and blood was perfused for selected times from 1 to 30 min. Platelet deposition on the surface was evaluated by 111Indium-labeled platelets. As percent stenosis increased, platelet deposition significantly increased (P less than 0.001), indicating a shear-induced cell activation. Analysis of the axial distribution of platelet deposition indicated that the apex, and not the flow recirculation zone distal to the apex, was the segment of greater platelet accumulation within 30 min of blood perfusion (P less than 0.001). These results also indicate that the severity of the acute platelet response to plaque rupture probably depends on the location of the rupture with relation to the apex of the plaque. .A Badimon L; Badimon JJ. .I 201414 .U 90009305 .S J Clin Invest 9001; 84(4):1145-54 .M alpha 1-Antitrypsin/*PK; Aerosols; Animal; Autoradiography; Bronchoalveolar Lavage Fluid/AN/EN; Capillary Permeability; Dogs; Electrophoresis, Polyacrylamide Gel; Female; Human; Immunohistochemistry; Lung/*ME; Lymph/AN; Pancreatopeptidase/AI; Pulmonary Alveoli/BS; Sheep; Support, U.S. Gov't, P.H.S.. .T Pulmonary deposition and clearance of aerosolized alpha-1-proteinase inhibitor administered to dogs and to sheep. .P JOURNAL ARTICLE. .W Augmentation of lung antiprotease levels may be an important therapeutic intervention in the prevention of pulmonary emphysema. We have administered aerosols of plasma-derived human alpha 1 proteinase inhibitor (A1PI) to the lungs of dogs and sheep to investigate (a) delivery of the protein to the distal air spaces of the lung; (b) maintenance of functional activity of the protein; and (c) flux of the protein across the components of the alveolar-capillary membrane. A1PI (26.4 mg/kg body weight) was administered as an aerosol to anesthetized animals; sheep were prepared for the chronic collection of lung lymph. Immunoperoxidase staining of lung tissue obtained 2 h after administration of A1PI demonstrated the presence of human A1PI on the surface of alveoli and distal bronchioles. Bronchoalveolar lavage fluid recovered at intervals after A1PI administration demonstrated time-dependent elevations of human A1PI levels with augmentation of lavage fluid antielastase activity in proportion to the content of human A1PI. Using radiolabeled A1PI as a tracer, we found that 32% of the aerosol was retained in the animals' lungs. Measurements of the rate of loss of A1PI from the lung and of the rate of appearance of human A1PI in plasma resulted in a calculated permeability of the alveolar-capillary membrane to A1PI of 3.49-6.39 X 10(-10) cm/s. Experiments using instrumented sheep allowed independent calculation of endothelial permeability to A1PI of 122-236 X 10(-10) cm/s and calculation of epithelial permeability of 4.70-4.81 X 10(-10) cm/s. Modeling of aerosol delivery of A1PI to humans using the results of these studies predicts that the ratio of plasma/alveolar levels of delivered A1PI will be 0.024, and that aerosolization of 175 mg A1PI/d will result in an A1PI alveolar fluid level of 1.0 mg/ml. Aerosol administration of A1PI may provide an efficient method of augmenting alveolar antiprotease levels. .A Smith RM; Traber LD; Traber DL; Spragg RG. .I 201415 .U 90009306 .S J Clin Invest 9001; 84(4):1155-9 .M Animal; Biological Transport; Blood-Brain Barrier/*; Diazepam/BL/*PK; In Vitro; Rats; Rats, Inbred Strains; Support, U.S. Gov't, P.H.S.. .T Plasma binding and transport of diazepam across the blood-brain barrier. No evidence for in vivo enhanced dissociation. .P JOURNAL ARTICLE. .W The tissue uptake of extensively plasma-bound compounds is reportedly inconsistent with the conventional free-drug hypothesis limiting transport to unbound moiety in rapid intracapillary equilibrium with bound complex. Instead, protein-mediated/cell surface enhancement of dissociation has been postulated to occur in the microvasculature. This possibility was investigated by studying the passive transport of diazepam across the blood-brain barrier. Microdialysis probes placed within the vena cava and brain cortex were used to directly compare steady-state, interstitial unbound diazepam levels in both Wistar and genetically analbuminemic rats. The absence of albumin in the latter increased the unbound fraction of diazepam by almost fivefold; however, in both groups, the ratio of unbound concentrations in brain and blood at equilibrium was equal to unity. If enhanced dissociation occurred in the microvasculature, then the unbound brain level should have been greater than that in the systemic circulation. It is probable that earlier findings suggestive of protein-mediated transport reflect a nonequilibrium phenomenon. Comparison of the extent of diazepam's in vivo binding in blood by microdialysis to that estimated in vitro using conventional equilibrium dialysis with microcells showed good agreement, thus validating a widely accepted assumption of equivalency of these two values. .A Dubey RK; McAllister CB; Inoue M; Wilkinson GR. .I 201416 .U 90009307 .S J Clin Invest 9001; 84(4):1160-6 .M Animal; DNA/GE; DNA Probes; Electrolytes/AN; Erythropoietin/*BI; Female; Hemodialysis; Human; Hydrogen-Ion Concentration; Kidney Failure, Chronic/ME; Kidney, Polycystic/*ME; Mice; Middle Age; Nucleic Acid Hybridization; Oxygen/AN; Proteins/AN; Radioimmunoassay; Support, Non-U.S. Gov't. .T Erythropoietin in polycystic kidneys. .P JOURNAL ARTICLE. .W Erythropoietin (EPO) formation in kidneys of 18 patients with autosomal dominant polycystic kidney disease (ADPKD) was investigated. In 12 patients on hemodialysis and in 6 patients with preterminal renal failure serum, EPO was 29 +/- 7 and 16 +/- 1.5 mU/ml and hemoglobin concentrations were 11.0 +/- 0.6 and 12.7 +/- 1.2 g/dl, respectively. Cyst fluid from a total of 357 renal cysts was obtained by either in vivo aspiration or immediately after nephrectomy. The cysts contained variable concentrations of bioactive EPO from undectable values up to 3.2 U/ml. A pronounced enrichment of EPO was observed in cysts with sodium concentrations greater than 100 mmol/liter, suggesting an association with proximal tubular malformations. The EPO concentrations in the cysts were neither correlated with the protein concentration nor with the oxygen pressure of the cyst fluid. Using a cDNA probe for human EPO, mRNA for EPO was localized in stroma cells of the cyst walls by an in situ hybridization technique. Our findings suggest that single interstitial cells juxtaposed to proximal tubular cysts may produce EPO independent of the oxygen pressure inside the cysts, which ameliorates the anemia during end-stage polycystic kidney disease. .A Eckardt KU; Mollmann M; Neumann R; Brunkhorst R; Burger HU; Lonnemann G; Scholz H; Keusch G; Buchholz B; Frei U; et al. .I 201417 .U 90009308 .S J Clin Invest 9001; 84(4):1167-73 .M Acetylcarnitine/BL/*ME/UR; Adult; Animal; Blood Gas Analysis; Carnitine/*AA/BL/*ME/UR; Exercise/*; Hemodynamics; Human; Hydroxybutyrates/BL; Lactates/BL; Mice; Muscles/*ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.. .T Carnitine and acylcarnitine metabolism during exercise in humans. Dependence on skeletal muscle metabolic state. .P JOURNAL ARTICLE. .W Carnitine metabolism has been previously shown to change with exercise in normal subjects, and in patients with ischemic muscle diseases. To characterize carnitine metabolism further during exercise, six normal male subjects performed constant-load exercise on a bicycle ergometer on two separate occasions. Low-intensity exercise was performed for 60 min at a work load equal to 50% of the lactate threshold, and high-intensity exercise was performed for 30 min at a work load between the lactate threshold and maximal work capacity for the individual. Low-intensity exercise was not associated with a change in muscle (vastus lateralis) carnitine metabolism. In contrast, from rest to 10 min of high-intensity exercise, muscle short-chain acylcarnitine content increased 5.5-fold while free carnitine content decreased 66%, and muscle total carnitine content decreased by 19% (all P less than 0.01). These changes in skeletal muscle carnitine metabolism were present at the completion of 30 min of high-intensity exercise, and persisted through a 60-min recovery period. With 30 min of high-intensity exercise, plasma short-chain and long-chain acylcarnitine concentrations increased by 46% and 23%, respectively. Neither exercise state was associated with a change in the urine excretion rates of free carnitine or acylcarnitines. Thus, alterations in skeletal muscle carnitine metabolism, characterized by an increase in acylcarnitines and a decrease in free and total carnitine, are dependent on the work load and, therefore, the metabolic state associated with the exercise, and are poorly reflected in the plasma and urine carnitine pools. .A Hiatt WR; Regensteiner JG; Wolfel EE; Ruff L; Brass EP. .I 201418 .U 90009310 .S J Clin Invest 9001; 84(4):1181-7 .M Animal; Bile Acids and Salts/*ME; Biliary Tract/SE; Cholesterol/*BI/SE; Cholesterol Esters/ME; Female; Liver/*ME; Lovastatin/PD; Membrane Lipids/ME; Microsomes, Liver/ME; Rats; Rats, Inbred Strains; Sterols/*ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Inappropriate hepatic cholesterol synthesis expands the cellular pool of sterol available for recruitment by bile acids in the rat. .P JOURNAL ARTICLE. .W These studies test the hypothesis that a major determinant of excessive biliary cholesterol secretion is a level of hepatic sterol synthesis that is inappropriately high relative to the needs of the liver cell for preserving cholesterol balance. Biliary cholesterol secretion was measured in vivo in two models after loading the hepatocyte with sterol by two different mechanisms. In the first model, cholesterol was delivered physiologically to the liver in chylomicron remnants. This resulted in a sixfold increase in cholesteryl ester content and marked suppression of cholesterol synthesis, but biliary cholesterol secretion remained essentially constant. In the second model, 3-hydroxy-3-methyl-glutaryl CoA reductase levels in the liver were markedly increased by chronic mevinolin (lovastatin) administration. Withdrawal of the inhibitor resulted in a sudden fivefold increase in the rate of sterol synthesis in the liver of the experimental animals that was inappropriately high for cellular needs. This excessive synthesis, in turn, was accompanied by a fivefold increase in the cholesteryl ester content, enrichment of microsomal membranes with cholesterol and, most importantly, by a threefold increase in the rate of biliary sterol secretion. As the rate of sterol synthesis gradually returned to normal over 48 h, the cholesterol ester content, the lipid composition of the microsomal membranes, and rate of cholesterol secretion into bile also returned to baseline values. These results further support the concept of functional compartmentalization of cholesterol in the hepatocyte. Derangements that cause an inappropriately high rate of sterol synthesis in the endoplasmic reticulum may lead to an expansion of that pool of cholesterol that is recruitable by bile acids and, hence, to greater situation of the bile. .A Bilhartz LE; Spady DK; Dietschy JM. .I 201419 .U 90009312 .S J Clin Invest 9001; 84(4):1196-205 .M Animal; Antigens, Neoplasm/IM; Calcium/*ME; Cell Adhesion Molecules/*ME; Endothelium, Vascular/*ME; Flow Cytometry; Guinea Pigs; Human; Lectins/*ME; Leukemia, Lymphocytic, Acute/*ME; Lymph Nodes/*ME; Mice; Rats; Stimulation, Chemical; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tetradecanoylphorbol Acetate/PD; Tumor Cells, Cultured. .T Adhesion molecules of cultured hematopoietic malignancies. A calcium-dependent lectin is the principle mediator of binding to the high endothelial venule of lymph nodes. .P JOURNAL ARTICLE. .W This study documents that a calcium-dependent phosphomanosyl-binding site on human lymphoid malignancies mediates attachment to the peripheral node high endothelial venule (PNHEV). The phorbol ester PMA coordinately upregulates lectin activity and binding to the PNHEV in the human T-lymphoblastic cell line Jurkat but not in the less phenotypically mature lines HSB2, Molt4, CEM, and HPB-ALL. In contrast, expression of CD18, CD2, and several common epitopes of the putative adhesion receptor gp90Hermes (CD44) did not correlate with attachment to PNHEV in this series of cell lines. Insensitivity to inhibition by the CD18 MAb TS 1.18, temperature and divalent cation requirements further distinguish the Jurkat-PNHEV adhesive interaction from CD11a/18- and CD2-mediated adhesion. The PMA-induced phenotypic changes in the Jurkat line parallel late thymocyte differentiation as well as lymphocyte activation, suggesting that expression of the endothelial-binding lectin may be linked to one or both of these processes. The lectin-like activity on Jurkat cells is functionally indistinguishable from those previously linked to PNHEV recognition in normal human lymphocytes, normal rat lymphocytes and both normal and malignant murine lymphoid cells. In the mouse, this activity is either contained in or functionally linked to a member of the LEC-CAM family gp90Mel14, suggesting that Jurkat cells express the human homologue of the murine nodal homing receptor. Thus cultured T lymphoblastic malignancies express a variety of potential endothelial adhesion molecules but use primarily a highly conserved surface lectin to interact with PNHEV. .A Stoolman LM; Ebling H. .I 201420 .U 90009313 .S J Clin Invest 9001; 84(4):1206-14 .M Adult; Amino Acid Sequence; Case Report; Child; Child, Preschool; Chromatography, DEAE-Cellulose; Collagen/AN/*GE; Cysteine/*GE; Electrophoresis, Polyacrylamide Gel; Female; Glycine/*GE; Human; Molecular Sequence Data; Mutation; Osteogenesis Imperfecta/*GE; Peptides/AN; Phenotype; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Osteogenesis imperfecta. The position of substitution for glycine by cysteine in the triple helical domain of the pro alpha 1(I) chains of type I collagen determines the clinical phenotype. .P JOURNAL ARTICLE. .W Skin fibroblasts grown from three individuals with osteogenesis imperfecta (OI) each synthesized a population of normal type I collagen molecules and additional molecules that had one or two alpha 1(I) chains that contained a cysteine residue within the triple-helical domain, a region from which cysteine normally is excluded. The patients had very different phenotypes. One patient with OI type I had a population of alpha 1(I) chains in which glycine at position 94 of the triple helix was substituted by cysteine; a patient with OI type III had a population of alpha 1(I) chains in which glycine at position 526 of the triple helix was substituted by cysteine; and the third patient, with OI type II, had a cysteine for glycine substitution at position 718 of the alpha 1(I) chain. From all three patients, molecules that contained two mutant chains formed interchain, intramolecular disulfide bonds, and although less stable to thermal denaturation than normal molecules, they were more stable than molecules that contained only a single mutant chain. These findings indicate that substitutions for glycine within the triple-helical domain of the alpha 1(I) chain are not invariably lethal and that their phenotypic effect largely depends on the nature of the substituting residue and its location in the chain. .A Starman BJ; Eyre D; Charbonneau H; Harrylock M; Weis MA; Weiss L; Graham JM Jr; Byers PH. .I 201421 .U 90009314 .S J Clin Invest 9001; 84(4):1215-9 .M Adenosine/GE; Apolipoproteins C/GE; Blotting, Northern; Blotting, Southern; Codon; Cytosine; DNA/AN/GE; Electrophoresis, Agar Gel; Electrophoresis, Gel, Two-Dimensional; Human; Mutation/*; Nucleic Acid Hybridization; Pedigree; Polymerase Chain Reaction; RNA/AN. .T A nonsense mutation in the apolipoprotein C-IIPadova gene in a patient with apolipoprotein C-II deficiency. .P JOURNAL ARTICLE. .W The apo C-II gene from a patient with apo C-II deficiency has been sequenced after amplification by the polymerase chain reaction. A substitution of an adenosine for a guanosine at position 3002 in exon 3 of the patient's gene was identified by sequence analysis. This mutation leads to the introduction of a premature termination codon (TAA) at a position corresponding to amino acid 37 of mature apo C-II and to the formation of a new Rsa I restriction enzyme site not present in the normal apo C-II gene. Amplification of DNA from family members by the polymerase chain reaction and digestion with Rsa I established that the patient is a true homozygote for the mutation. Analysis of the patient's plasma by two-dimensional gel electrophoresis and immunoblotting detected an apo C-II that exhibited abnormal electrophoretic mobility. We propose that the C to A substitution in the apo C-IIPadova gene is the primary genetic defect that leads to premature termination and the synthesis of a truncated 36 amino acid apo C-II that is unable to activate lipoprotein lipase. .A Fojo SS; Lohse P; Parrott C; Baggio G; Gabelli C; Thomas F; Hoffman J; Brewer HB Jr. .I 201422 .U 90009315 .S J Clin Invest 9001; 84(4):1220-5 .M Adult; Benzodiazepinones/*PD; Cholecystokinin/BL/*PH; Eating; Gallbladder/*DE/PH; Gastric Emptying/*DE; Human; Male; Radioimmunoassay; Receptors, Cholecystokinin/*AI; Support, U.S. Gov't, P.H.S.. .T Effects of a novel cholecystokinin (CCK) receptor antagonist, MK-329, on gallbladder contraction and gastric emptying in humans. Implications for the physiology of CCK. .P JOURNAL ARTICLE. .W To explore the physiology of cholecystokinin (CCK) in humans, we investigated the effect on gallbladder contraction and gastric emptying of a recently developed CCK receptor antagonist, MK-329. In a double-blind, four-period crossover study eight subjects received single doses of 0.5, 2, or 10 mg MK-329, or placebo, followed by an intravenous infusion of CCK-8 (30 pmol/kg.h). In placebo-treated subjects gallbladder volumes decreased on average to 43% of initial volumes after 2 h of CCK infusion. MK-329 caused a dose-dependent inhibition of CCK-stimulated gallbladder contraction with 10 mg producing complete blockade (P less than 0.01, cf. placebo). Gallbladder contraction and gastric emptying rates after a mixed meal were then measured in a two-period crossover study. Subjects received placebo or 10 mg of MK-329 2 h before eating. Gastric emptying of both solids and liquids was measured simultaneously by gamma scintigraphy. In placebo-treated subjects plasma CCK levels increased postprandially to 2.3 pM, gallbladder volumes decreased 68.4 +/- 3.8% (SE), and the times for 50% emptying of liquids and solids from the stomach were 58 +/- 10 and 128 +/- 8 min, respectively. In MK-329-treated subjects there was a marked elevation in peak CCK levels to 13.8 pM (P less than 0.01, cf. placebo), and gallbladder contraction was completely inhibited. Solid and liquid emptying rates were unaffected. These findings demonstrate that (a) MK-329 is a potent, orally active antagonist of CCK in humans, and (b) CCK is the major regulator of postprandial gallbladder contraction. These data also support the concept of negative feedback regulation of CCK secretion and suggest that mechanisms other than CCK play a dominant role in the regulation of postprandial gastric emptying rates. .A Liddle RA; Gertz BJ; Kanayama S; Beccaria L; Coker LD; Turnbull TA; Morita ET. .I 201423 .U 90009316 .S J Clin Invest 9001; 84(4):1226-35 .M Adult; Amino Acids/BL; Female; Fibrinogen/AN/BI; Fibronectins/*BI/BL; Glycine/BL; Hippurates/UR; Human; Hydrolysis; Male; Mass Fragmentography; Middle Age; Nitrogen Isotopes; Reference Values; Support, U.S. Gov't, P.H.S.; Wounds and Injuries/*BL. .T Plasma fibronectin synthesis in normal and injured humans as determined by stable isotope incorporation. .P JOURNAL ARTICLE. .W In humans, plasma fibronectin decreases early after operative injury, burn, or trauma, followed by a rapid restoration with a secondary decline typically observed if such patients become septic. We determined the rate of plasma fibronectin and plasma fibrinogen synthesis in normal subjects and injured patients using a stable isotope incorporation technique with [15N]glycine. During a constant 14-h infusion of [15N]glycine, the enrichment of [15N]glycine in both the free plasma glycine precursor pool as well as the urinary hippurate pool was determined; the latter used as an estimate of intracellular hepatic precursor enrichment. [15N]Glycine enrichment in both plasma fibronectin and fibrinogen was also quantified. The synthesis rate (Js/V) expressed in micrograms per milliliter of plasma per hour and the fractional synthesis rate (FSR) expressed as percentage of the plasma pool produced per day were determined. In normal subjects, the FSR for plasma fibronectin using 15N enrichment into urinary hippurate was 35.35 +/- 1.46%/d, whereas the Js/V was 4.45 +/- 0.19 micrograms/ml plasma per h. In normal subjects, the FSR for plasma fibronectin using 15N enrichment into free plasma glycine was 14.73 +/- 0.63%/d, whereas the Js/V was 1.98 +/- 0.09 micrograms/ml plasma per h. Early (2-3 d) after burn injury, fibronectin synthesis was increased (Js/V = 5.74 +/- 0.36; P less than 0.05), whereas later after injury, fibronectin synthesis began to decline (Js/V = 3.52 +/- 0.24; P less than 0.05) based on 15N enrichment of urinary hippurate. In contrast, the Js/V and FSR of plasma fibrinogen, a well-documented acute-phase plasma protein, revealed a sustained elevation (P less than 0.05) after injury in both the trauma and burn patients. Thus, plasma fibronectin synthesis is elevated early postinjury, which may contribute to the rapid restoration of its blood level. However, once fibronectin levels have normalized, the synthesis of plasma fibronectin appears to decline. .A Thompson C; Blumenstock FA; Saba TM; Feustel PJ; Kaplan JE; Fortune JB; Hough L; Gray V. .I 201424 .U 90009317 .S J Clin Invest 9001; 84(4):1236-42 .M Adult; Alanine/*GE; Amino Acid Sequence; Antithrombin III/*GE; Base Sequence; Binding Sites; DNA/AN; DNA Polymerase I/ME; Electrophoresis, Agar Gel; Female; Human; Molecular Sequence Data; Mutation/*; Nucleic Acid Hybridization; Polymerase Chain Reaction; Support, Non-U.S. Gov't. .T Molecular characterization of antithrombin III (ATIII) variants using polymerase chain reaction. Identification of the ATIII Charleville as an Ala 384 Pro mutation. .P JOURNAL ARTICLE. .W The genes of seven structural mutants of antithrombin III (ATIII), presenting either defective serine protease reactivity or abnormal heparin binding, were analyzed. The polymerase chain reaction (PCR) was used to amplify the corresponding gene exon and the mutation was identified by either dot blot analysis using a battery of allele-specific oligonucleotide probes or sequencing. Variants Paris and Paris 2 were identified as Arg 47 Cys mutations, and Clichy, Clichy 2, and Franconville were found to be Pro 41 Leu mutations. All five are heparin binding-site variants. ATIII Avranches is an Arg 393 His mutation and ATIII Charleville is an Ala 384 Pro mutation. These two mutations impair the reactive site of the molecule. ATIII Charleville is a new mutation of the reactive center, as predicted by previous biochemical data. The position of this new mutation, together with the other previously described mutations of the reactive center, sheds light on the molecular function of this site in inhibiting thrombin. Finally, genomic amplification by PCR is a powerful technique for the fast identification of antithrombin III mutations and their homozygous/heterozygous status, and should be useful for predicting thrombotic risk. .A Molho-Sabatier P; Aiach M; Gaillard I; Fiessinger JN; Fischer AM; Chadeuf G; Clauser E. .I 201425 .U 90009318 .S J Clin Invest 9001; 84(4):1243-52 .M Amino Acid Sequence; Base Sequence; Cloning, Molecular; DNA/*GE; Electrophoresis, Agar Gel; Elliptocytosis, Hereditary/*GE; Exons; Gene Library; Human; Introns; Molecular Sequence Data; Mutation/*; Polymerase Chain Reaction; Spectrin/*GE; Support, U.S. Gov't, P.H.S.. .T Sequence and exon-intron organization of the DNA encoding the alpha I domain of human spectrin. Application to the study of mutations causing hereditary elliptocytosis. .P JOURNAL ARTICLE. .W We have determined the exon-intron organization and the nucleotide sequence of the exons and their flanking intronic DNA in cloned genomic DNA that encodes the first 526 amino acids of the alpha I domain of the human red cell spectrin polypeptide chain. From the gene sequence we designed oligonucleotide primers to use in the polymerase chain reaction technique to amplify the appropriate exons in DNA from individuals with three variants of hereditary elliptocytosis characterized by the presence of abnormal alpha I spectrin peptides, 46-50 and 65-68 kD in size, in partial tryptic digests of spectrin. The alpha I/68-kD abnormality resulted from a duplication of leucine codon 148 in exon 4: TTG-CTG to TTG-TTG-CTG. The alpha I/50a defect was associated in different individuals with two separate single base changes in exon 6: CTG to CCG (leucine to proline) encoding residue 254, and TCC to CCC (serine to proline) encoding residue 255. In another individual with the alpha I/50a polypeptide defect, the nucleotide sequence encoding amino acid residues 221 through 264 was normal. The alpha I/50b abnormality resulted from a single base change of CAG (glutamine) to CCG (proline) encoding residue 465 in exon 11 in two unrelated individuals. In a third individual with alpha I/50b-kD hereditary elliptocytosis, the entire exon encoding residues 445 through 490 was normal. The relationship of the alpha I domain polypeptide structure to these mutations and the organization of the gene is discussed. .A Sahr KE; Tobe T; Scarpa A; Laughinghouse K; Marchesi SL; Agre P; Linnenbach AJ; Marchesi VT; Forget BG. .I 201426 .U 90009319 .S J Clin Invest 9001; 84(4):1253-9 .M Animal; Dexamethasone/TU; Disease Models, Animal; Glucose/CF; Haemophilus influenzae/IP; Lactates/CF; Lipopolysaccharides/TO; Male; Meningitis, Haemophilus/CI/*DT/ME; Proteins/AN; Rabbits; Tumor Necrosis Factor/CF/IM/*TU. .T Tumor necrosis factor in mediating experimental Haemophilus influenzae type B meningitis. .P JOURNAL ARTICLE. .W Tumor necrosis factor (TNF) could possibly be instrumental in mediating injury to the CNS during bacterial meningitis. In CSF of rabbits with meningitis induced with Haemophilus influenzae type b (Hib) lipooligosaccharide (LOS), TNF activity was first detected 45 min after intracisternal (IC) injection of 20 ng Hib LOS and white blood cells (WBC) first appeared 75 min later. The peak TNF activity (45 ng/ml) was observed at 120 min after IC and persisted for 5 h. When 1-2 X 10(7) CFU of Hib was used to induce meningitis, peak CSF TNF activity was comparable with that after 20 ng Hib LOS, but the activity persisted for 14 h. Dexamethasone (DXM) (1 mg/kg per i.v.) given 1 h before or simultaneously with IC Hib LOS reduced significantly TNF activity and meningeal inflammation. Goat anti-human TNF alpha antibodies given IC with 20 ng Hib LOS or 2 X 10(6) CFU of Hib resulted in a significant reduction in CSF TNF concentrations, which was also associated with reduced meningeal inflammation in Hib LOS-inoculated animals. We conclude that TNF participates in mediating meningeal inflammation associated with Hib experimental meningitis, and that DXM, when given before or with Hib LOS, inhibits CSF TNF production and modulates the meningeal inflammatory response. .A Mustafa MM; Ramilo O; Olsen KD; Franklin PS; Hansen EJ; Beutler B; McCracken GH Jr. .I 201427 .U 90009321 .S J Clin Invest 9001; 84(4):1267-75 .M Animal; Catecholamines/AN/BL; Dogs; Down-Regulation (Physiology)/*; Heart Failure, Congestive/ME/*PP; Hemodynamics; In Vitro; Myocardium/ME; Neurons/ME/*PH; Norepinephrine/ME; Receptors, Adrenergic, Beta/ME/*PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tyramine/PD. .T Decreased adrenergic neuronal uptake activity in experimental right heart failure. A chamber-specific contributor to beta-adrenoceptor downregulation. .P JOURNAL ARTICLE. .W The reduction of myocardial beta-adrenoceptor density in congestive heart failure has been thought to be caused by agonist-induced homologous desensitization. However, recent evidence suggests that excessive adrenergic stimulation may not produce myocardial beta-receptor downregulation unless there is an additional defect in the local norepinephrine (NE) uptake mechanism. To investigate the association between beta-adrenoceptor regulation and NE uptake activity, we carried out studies in 30 dogs with right heart failure (RHF) produced by tricuspid avulsion and progressive pulmonary artery constriction and 23 sham-operated control dogs. We determined NE uptake activity by measuring accumulation of [3H]NE in tissue slices, NE uptake-1 carrier density by [3H]mazindol binding and beta-adrenoceptor density by [3H]dihydroalprenolol binding. Compared with sham-operated dogs, RHF dogs showed a 26% decrease in beta-adrenoceptor density, a 51% reduction in NE uptake activity, and a 57% decrease in NE uptake-1 carrier density in their right ventricles. In addition, right ventricle beta-receptor density correlated significantly with NE uptake activity and NE uptake-1 carrier density. In contrast, neither NE uptake activity nor beta-receptor density in the left ventricle and renal cortex was affected by RHF. Thus, the failing myocardium is associated with an organ- and chamber-specific subnormal neuronal NE uptake. This chamber-specific loss of NE uptake-1 carrier could effectively reduce local NE clearance, and represent a local factor that predisposes the failing ventricle to beta-adrenoceptor downregulation. .A Liang CS; Fan TH; Sullebarger JT; Sakamoto S. .I 201428 .U 90009322 .S J Clin Invest 9001; 84(4):1276-86 .M Animal; Capillary Permeability/*DE; Fibrin/ME; Granulocytes/*DE; Mast Cells/*ME; Mice; Mice, Inbred Strains; Substance P/*PD; Support, U.S. Gov't, P.H.S.. .T Substance P-induced augmentation of cutaneous vascular permeability and granulocyte infiltration in mice is mast cell dependent. .P JOURNAL ARTICLE. .W The undecapeptide substance P is thought to mediate both vasodilatation and augmented vascular permeability when released from sensory nerve endings in the skin. Substance P also induces mast cell degranulation in vitro or in vivo. However, the extent to which substance P-induced changes in vascular permeability are mast cell-dependent is unclear. We investigated this issue by injecting substance P and certain related peptides (substance P1-4, substance P4-11) into the skin of genetically mast cell-deficient WBB6F1-W/W or WCB6F1- SI/SId mice the congenic normal (+/+) mice, and W/W mice which had undergone selective local repair of their mast cell deficiency by intradermal injection of IL-3-dependent mast cells generated in vitro from the bone marrow cells of the congenic +/+ mice. Substance P induced significant augmentation of vascular permeability and significant cutaneous swelling when injected into normal mice at doses as low as 2 pmol i.d. Substance P also induced granulocyte infiltration, although the infiltrate were modest and were seen at doses of peptide from 5 to more than 20-fold higher than those required for induction of tissue swelling. The effects of substance P on tissue swelling, vascular permeability, and granulocyte infiltration were virtually entirely mast cell dependent. By contrast, substance P1-4 was inactive in our assays at 25 nmol/site, and substance P4-11 induced modest augmentation of vascular permeability, which was at least in part mast cell independent. .A Yano H; Wershil BK; Arizono N; Galli SJ. .I 201429 .U 90009324 .S J Clin Invest 9001; 84(4):1295-301 .M Animal; Animals, Newborn; Biological Transport, Active; Calcium/*ME; Chlorides/ME; Cytoplasm/AN; Female; Lung/EM/UL; Pregnancy; Pulmonary Alveoli/ME; Pulmonary Surfactants/*ME; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't. .T Perinatal changes in lung surfactant calcium measured in situ. .P JOURNAL ARTICLE. .W Calcium ion is thought to play a role in the structure and function of pulmonary surfactant after secretion into the alveolar space. Since fetal lung liquid calcium concentration is inadequate for this hypothesized role, at a time when optimal surfactant function is necessary for survival, we speculated that the necessary calcium is secreted with the surfactant material, i.e., in the lamellar body. Lungs from rat fetuses at 20, 21, and 22 d gestation, and also from newborn rats at 3-5 h, 1 and 3 d, were rapidly frozen, sectioned, freeze-dried, and examined cold (-100 degrees C) in a transmission electron microscope equipped with a fully quantitative energy-dispersive x-ray detector and analyzer. X-ray spectra were collected from the lamellar bodies and cytoplasm of type II cells at each time point. Lamellar body calcium concentration in the fetus was approximately twice that of the adult (70 +/- 4 vs. 37 +/- 2 mmol/kg dry wt +/- SEM, P less than 0.01), and it decreased rapidly after birth to adult levels. Apically located lamellar bodies in the fetus have a significantly higher calcium concentration than those in a perinuclear position (76 +/- 4 vs. 52 +/- 3, P less than 0.01). There is significant correlation of calcium and chloride concentrations in lamellar bodies, suggesting that factors responsible for the distribution of chloride, i.e., pH, may also be responsible for the accumulation of calcium by these organelles. These results show that mature calcium transport in lamellar bodies is achieved prenatally in the rat, and suggest that the calcium required for normal surfactant function at birth is secreted with the lamellar body. .A Eckenhoff RG. .I 201430 .U 90009326 .S J Clin Invest 9001; 84(4):1314-9 .M Hepatitis B Surface Antigens/*IM; Hepatitis B Virus/*IM; Human; Protein Precursors/*IM; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; T-Lymphocytes/*IM; Viral Envelope Proteins/*IM; Viral Hepatitis Vaccines/*IM. .T The preS1 antigen of hepatitis B virus is highly immunogenic at the T cell level in man. .P JOURNAL ARTICLE. .W 14 hepatitis B vaccine recipients who showed high titers of anti-hepatitis B surface antibodies in serum after booster immunization with a polyvalent hepatitis B surface antigen vaccine that contained trace amounts of hepatitis B virus (HBV) preS1 and preS2 envelope antigens were studied for their in vitro T cell response to these antigens. All 14 subjects displayed a significant proliferative T cell response to the S/p25 envelope region encoded polypeptide; 8 also responded to preS1, while only 1 showed a significant level of T cell proliferation to preS2. Limiting dilution analysis demonstrated that the frequency of preS-specific T cells in two of these vaccine recipients was higher than that of S/p25-specific T cells. T cell cloning was then performed and a total of 29 HBV envelope antigen-reactive CD4+ cloned lines were generated from two preS-responsive vaccines. 21 of these lines were S/p25 specific, 7 preS1 specific, and 1 preS2 specific. Taken together, all these results suggest that the preS1 antigen may function as a strong T cell immunogen in man. .A Ferrari C; Penna A; Bertoletti A; Cavalli A; Valli A; Schianchi C; Fiaccadori F. .I 201431 .U 90009328 .S J Clin Invest 9001; 84(4):1325-33 .M Adipose Tissue/CY/*ME; Albumins/*PH; Animal; Liver/CY/*ME; Male; Models, Biological; Myocardium/CY/*ME; Oleic Acids/AN/*PK; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T At physiologic albumin/oleate concentrations oleate uptake by isolated hepatocytes, cardiac myocytes, and adipocytes is a saturable function of the unbound oleate concentration. Uptake kinetics are consistent with the conventional theory. .P JOURNAL ARTICLE. .W To reexamine the role of albumin in cellular uptake of long chain fatty acids, we measured [3H]oleate uptake by isolated hepatocytes, adipocytes, and cardiac myocytes from incubations containing oleate/albumin complexes at molar ratios from 0.01:1 to 2:1. For each ratio the uptake was studied over a wide range of albumin concentrations. In all three cell types and at any given oleate/albumin ratio, the uptake appeared saturable with increasing concentrations of oleate:albumin complexes despite the fact that the unbound oleate concentration for each molar ratio is essentially constant. However, the "Km" but not the "Vmax" of these pseudosaturation curves was influenced by substrate availability. At low albumin concentrations, uptake velocities did not correlate with unbound oleate concentrations. However, observed and expected uptake velocities coincided at albumin concentrations approaching physiologic levels and were a saturable function of the oleate/albumin ratios and the consequent unbound oleate concentrations employed. Hence, under the experimental conditions employed in this study using a variety of suspended cell types, oleate uptake kinetics were consistent with the conventional theory at physiologic concentrations of albumin. .A Sorrentino D; Robinson RB; Kiang CL; Berk PD. .I 201432 .U 90009330 .S J Clin Invest 9001; 84(4):1340-4 .M Cross-Linking Reagents; Electrophoresis, Polyacrylamide Gel; Erythroid Progenitor Cells/ME; Erythropoiesis; Erythropoietin/*ME; Human; Polycythemia Vera/*ME; Receptors, Endogenous Substances/*ME; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Erythropoietin receptors in polycythemia vera. .P JOURNAL ARTICLE. .W The role of erythropoietin (EP) in polycythemia vera (PV) is controversial, with some experiments suggesting that erythroid progenitors in PV are exquisitely sensitive to EP and EP dependent, and others suggesting that PV progenitors are EP independent. We have examined the characteristics of the EP receptor (EP-R) on erythroid colony-forming cells (ECFC) from patients with PV. In contrast to normal ECFC, which have two classes of EP-R, with 20% showing high affinity (Kd = 0.13 nM; range, 0.04-0.20 nM) and the remainder lower affinity (Kd = 0.37 nM; range, 0.28-0.57 nM), PV ECFC show a single class of 851 low affinity EP-R with Kd = 0.72 nM (range, 0.36-0.85 nM). ECFC from patients with secondary (EP driven) polycythemia or anemia show two classes of EP-R (Kd = 0.18 and 1.10 nM, respectively). Attempts to remove tightly bound EP from putative high affinity EP-R in PV did not reveal any higher affinity receptors. Determination of molecular size by crosslinking showed two proteins of 90 and 100 kD similar to those seen with normal EP-R. These studies indicate the PV ECFC have EP-R that are structurally similar to normal EP-R but lack the higher binding affinity for EP. .A Means RT Jr; Krantz SB; Sawyer ST; Gilbert HS. .I 201433 .U 90009331 .S J Clin Invest 9001; 84(4):1345-8 .M Animal; Autoimmune Diseases/*DT; Blotting, Northern; Diabetes Mellitus, Experimental/*DT; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Pancreas/PA; Recombinant Proteins/TU; Support, Non-U.S. Gov't; Tumor Necrosis Factor/BI/*TU. .T Recombinant human tumor necrosis factor alpha suppresses autoimmune diabetes in nonobese diabetic mice. .P JOURNAL ARTICLE. .W We previously reported that administration of a streptococcal preparation (OK-432) inhibited insulitis and development of autoimmune diabetes in nonobese diabetic (NOD) mice and BB rats as animals models of insulin-dependent diabetes mellitus. In this study, we screened various cytokines that could be induced by OK-432 in vivo, for their preventive effect against diabetes in NOD mice. Among recombinant mouse IFN gamma, human IL1 alpha, human IL2, mouse granulocyte-macrophage colony-stimulating factor and human TNF alpha, only human TNF alpha suppressed insulitis and significantly (P less than 0.001) inhibited development of diabetes. NOD mice were the lowest producers of the mRNA of TNF and serum TNF on stimulation with OK-432 or with IFN gamma plus LPS, compared with C57BL/6, C3H/He, and Balb/c mice. The results imply a role for low productivity of TNF in the pathogenesis of autoimmune diabetes in NOD mice. .A Satoh J; Seino H; Abo T; Tanaka S; Shintani S; Ohta S; Tamura K; Sawai T; Nobunaga T; Oteki T; et al. .I 201434 .U 90009332 .S J Clin Invest 9001; 84(4):1349-54 .M alpha 1-Antitrypsin/BI/*DF/PD; Adult; Aerosols; Blotting, Western; Bronchoalveolar Lavage Fluid/AN; DNA, Recombinant; Electrophoresis, Polyacrylamide Gel; Female; Human; Male; Middle Age; Neutrophils/*EN; Pancreatopeptidase/*AI; Recombinant Proteins/PD; Respiratory System/*EN. .T Recombinant DNA-produced alpha 1-antitrypsin administered by aerosol augments lower respiratory tract antineutrophil elastase defenses in individuals with alpha 1-antitrypsin deficiency. .P JOURNAL ARTICLE. .W Alpha 1-Antitrypsin (alpha 1AT) deficiency is characterized by insufficient amounts of alpha 1AT to protect the lower respiratory tract from neutrophil elastase, resulting in emphysema. Yeast-produced recombinant alpha 1AT (rAAT) has normal antielastase function but is associated with high renal clearance, thus obviating chronic intravenous administration. As an alternative, we evaluated aerosol administration of rAAT to alpha 1AT-deficient individuals. After aerosol administration of single doses of 10-200 mg of rAAT, epithelial lining fluid (ELF) alpha 1AT antineutrophil elastase defenses were augmented in proportion to the dose of rAAT administered. ELF alpha 1AT levels and antineutrophil elastase capacity 4 h after 200 mg rAAT aerosol were increased 40-fold over preaerosol levels, and were fivefold increased over baseline at 24 h after aerosol administration. rAAT was detectable in serum after aerosol, indicating that the lower respiratory tract epithelium may be permeable to rAAT, and that aerosolized rAAT is capable of gaining access to lung interstitium. No adverse clinical effects were noted. These observations demonstrate that aerosol administration of rAAT is safe and results in significant augmentation of lung antineutrophil elastase defenses, suggesting this method is a feasible approach to therapy. Because this approach is clinically unproven, further studies will be necessary to establish the long-term clinical efficacy of aerosol therapy in alpha 1AT deficiency. .A Hubbard RC; McElvaney NG; Sellers SE; Healy JT; Czerski DB; Crystal RG. .I 201435 .U 90009333 .S J Clin Invest 9001; 84(4):1355-61 .M Acid Phosphatase/AN; Animal; Chromatography, Gas; Intestinal Mucosa/CY/*SE/UL; Intestine, Small/CY/*SE/UL; Lipids/AN; Male; Microvilli/AN; Phospholipids/AN; Phosphorus/AN; Pulmonary Surfactants/AN; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Surface Tension; Surface-Active Agents/*. .T Intestinal surfactant-like material. A novel secretory product of the rat enterocyte. .P JOURNAL ARTICLE. .W Surface-active phospholipid-containing particles are traditionally considered to be the product of type II pneumocytes. We now demonstrate membrane-bound lamellar cytoplasmic organelles in adult and suckling rat enterocytes that are densely reactive with phospholipid-staining reagents. These structures were seen in the basolateral space, within the intercellular junctions, and unraveling on the lumenal surface, and were more abundant after fat feeding. Light scrapings of intestinal mucosa and lumenal washings that contained these bodies, as evidenced by morphology and biochemical analysis, lowered surface tension in a pulsating bubble assay. Production by normal enterocytes of material with surfactant-like appearance and properties demonstrates that these structures are present in extrapulmonary epithelia, and extends the possible range of their function beyond gaseous exchange, e.g., solute exchange or lubrication on membrane surfaces. .A DeSchryver-Kecskemeti K; Eliakim R; Carroll S; Stenson WF; Moxley MA; Alpers DH. .I 201436 .U 90009334 .S J Clin Invest 9001; 84(4):1362-6 .M Acute Disease; Animal; Deferoxamine/*TU; Disease Models, Animal; Iron/*PO; Iron Chelates/*TU; Male; Mice; Support, U.S. Gov't, P.H.S.. .T Acute iron poisoning. Rescue with macromolecular chelators. .P JOURNAL ARTICLE. .W Acute iron intoxication is a frequent, sometimes life-threatening, form of poisoning. Present therapy, in severe cases, includes oral and intravenous administration of the potent iron chelator, deferoxamine. Unfortunately, high dose intravenous deferoxamine causes acute hypotension additive with that engendered by the iron poisoning itself. To obviate this problem, we have covalently attached deferoxamine to high molecular weight carbohydrates such as dextran and hydroxyethyl starch. These macromolecular forms of deferoxamine do not cause detectable decreases in blood pressure of experimental animals, even when administered intravenously in very large doses, and persist in circulation much longer than the free drug. These novel iron-chelating substances, but not deferoxamine itself, will prevent mortality from otherwise lethal doses of iron administered to mice either orally or intraperitoneally. Further reflecting this enhanced therapeutic efficacy, the high molecular weight iron chelators also abrogate iron-mediated hepatotoxicity, suppressing the release of alanine aminotransferase. We conclude that high molecular weight derivatives of deferoxamine hold promise for the effective therapy of acute iron intoxication and may also be useful in other clinical circumstances in which control of free, reactive iron is therapeutically desirable. .A Mahoney JR Jr; Hallaway PE; Hedlund BE; Eaton JW. .I 201437 .U 90009335 .S J Clin Invest 9001; 84(4):1367-71 .M Antibodies, Monoclonal/DU; Autoradiography; Chronic Disease; DNA, Viral/BL; Genes, Viral/*; Heat; Hepatitis B Surface Antigens/IM; Hepatitis B Virus/GE/*IP; Human; IgM/IM; Liver Diseases/DI; Polymerase Chain Reaction; Support, U.S. Gov't, P.H.S.. .T Rapid identification of low level hepatitis B-related viral genome in serum. .P JOURNAL ARTICLE. .W A sensitive and specific method has been developed to detect hepatitis B virus (HBV) in serum. The method involves two steps: the capture of viral genome from serum using a high affinity IgM monoclonal antibody directed against a common a domain epitope found on the envelope, and the amplification of viral DNA by the polymerase chain reaction (PCR). The amplification is initiated using "generic" primers derived from the core and pre-core sequences which are highly conserved amongst the hepadnaviruses. This rapid technique detects less than 10 infectious virions and may be useful in the study of individuals with acute and chronic liver disease of unknown etiology. .A Liang TJ; Isselbacher KJ; Wands JR. .I 201438 .U 90009365 .S J Clin Pathol 9001; 42(9):1001 .M Carcinoma, Squamous Cell/*CO; Human; Temporal Arteritis/*CO; Tongue/*BS; Tongue Neoplasms/*CO. .T Giant cell arteritis of the tongue associated with squamous cell carcinoma [letter] [see comments] .P LETTER. .A Misselevitch I; Fradis M; Podoshin L; Barel E; Boss JH. .I 201439 .U 90009366 .S J Clin Pathol 9001; 42(9):1001-2 .M Adult; Capillaries/PA; Case Report; Churg-Strauss Syndrome/*PA; Human; Male. .T Small blood vessel disease in allergic granulomatous angiitis (Churg-Strauss syndrome) [letter] .P LETTER. .A Lichtig C; Ludatscher R; Eisenberg E; Bental E. .I 201440 .U 90009367 .S J Clin Pathol 9001; 42(9):1002 .M Carcinoma, Basal Cell/*PA; Fluorescence/*; Formaldehyde/*; Human. .T Fluorescence in pigmented basal cell carcinoma caused by formaldehyde [letter] .P LETTER. .A Deshmukh SD; Thakar PG. .I 201441 .U 90009368 .S J Clin Pathol 9001; 42(9):1002-3 .M Human; Meningeal Neoplasms/UL; Meningioma/*UL; Neoplasm Recurrence, Local/*; Nucleolus Organizer Region/*PA; Predictive Value of Tests; Silver; Stains and Staining/*. .T Value of AgNOR method in predicting recurrence of meningioma [letter] .P LETTER. .A Boon AP; Sharif H. .I 201442 .U 90009369 .S J Clin Pathol 9001; 42(9):1003-4 .M Carcinoid Tumor/*UL; Carcinoma, Oat Cell/*UL; Human; Lung Neoplasms/*UL; Nucleolus Organizer Region/*; Silver; Stains and Staining/*. .T Inability of AgNOR counts to differentiate between bronchial carcinoid tumours and small cell carcinoma of the bronchus [letter] .P LETTER. .A Benbow EW; Cromie CJ. .I 201443 .U 90009370 .S J Clin Pathol 9001; 42(9):1004-5 .M Campylobacter/*IP; Gastric Mucosa/*MI; Human; Rosaniline Dyes/*. .T Simple carbolfuchsin staining for showing C pylori and other spiral bacteria in gastric mucosa [letter] .P LETTER. .A Rocha GA; Queiroz DM; Mendes EN; Lage AP; Barbosa AJ. .I 201444 .U 90009371 .S J Clin Pathol 9001; 42(9):1005-6 .M Drug Tolerance; Penicillins/*PD; Streptococcus/*DE. .T Tolerance to penicillin in streptococci of viridans group [letter] .P LETTER. .A Woolfrey BF; Lally RT. .I 201445 .U 90009372 .S J Clin Pathol 9001; 42(9):1006 .M Drug Tolerance; Penicillins/*PD; Streptococcus/*DE. .T Tolerance to penicillin in streptococci of viridans group [letter] .P LETTER. .A Richards J; Perry J; McMaster A; Freeman R; Gould FK. .I 201446 .U 90009373 .S J Clin Pathol 9001; 42(9):1006-7 .M Colonic Neoplasms/*PA; Human; Prognosis; Rectal Neoplasms/*PA. .T Prognostic variables in large bowel cancer [letter] .P LETTER. .A Jass JR. .I 201447 .U 90009374 .S J Clin Pathol 9001; 42(9):1007-8 .M Biopsy, Needle/*; Human; Thyroid Diseases/*PA. .T Fine needle aspiration of thyroid nodules [letter] .P LETTER. .A Kung IT. .I 201448 .U 90009375 .S J Clin Pathol 9001; 42(9):897-901 .M Autopsy/*/SN; Hospitals, Teaching/*ST; Human; Medical Audit/*MT; Northern Ireland; Surgery, Operative/MO. .T Necropsies in clinical audit. .P JOURNAL ARTICLE. .W The need for specialised forms of clinical audit was highlighted by the report of the Confidential Enquiry into Perioperative Deaths (CEPOD). Necropsy rates in a Northern Ireland teaching hospital were studied with particular reference to perioperative deaths. To provide an overall context for these observations, the pattern of the necropsy services in Northern Ireland as a whole was also determined. For 600 consecutive deaths in a major teaching hospital, the overall necropsy rate was 180 (30%). In the 74 perioperative deaths in this group (as defined by the CEPOD) the necropsy rate was 26 (35%), compared with 16 out of 72 (22%) for other surgical deaths and 89 out of 386 (23%) for medical cases. More coroners' necropsies were carried out in the perioperative group. These figures are within the range of the CEPOD experience. In 1987, in the whole of Northern Ireland, there were 8859 hospital deaths, 520 (5.9%) hospital necropsies, and 516 (5.8%) coroners' necropsies, giving an overall necropsy rate of 11.7%. Outside the two major Belfast teaching hospitals, however, there were 6799 hospital deaths, 76.6% of all hospital deaths for Northern Ireland. In this group there were 180 (2.6%) hospital necropsies and 383 (5.6%) coroners' cases, the overall necropsy rate being only 8.2%. These wide variations reflect the fact that the number of pathologists in post in the peripheral areas of the province falls substantially short of levels recommended by the Royal College of Pathologists. If clinical audit along CEPOD lines is to be effective nationally, more emphasis should be placed on the value of necropsy and local deficiencies in provision will have to be identified and remedied. It is suggested that this could be achieved by combining audit provisions with budgetary incentives. .A Anderson NH; Shanks JH; McCluggage GW; Toner PG. .I 201449 .U 90009378 .S J Clin Pathol 9001; 42(9):912-8 .M Autopsy/*/SN; Child; England; Female; Heart Defects, Congenital/*PA/SU; Hospital Departments/*ST; Human; Male; Medical Audit/*; Retrospective Studies; Surgery Department, Hospital/*ST. .T Postmortem audit in a paediatric cardiology unit. .P JOURNAL ARTICLE. .W Postmortem examinations performed on 76 children with a clinical diagnosis of congenital heart disease were reviewed retrospectively and compared with the findings before death. Both operated and unoperated cases were studied over a three year period. Despite intensive investigation during life, there was a high rate of unsuspected abnormalities at necropsy (80%): 29 cases had undiagnosed additional cardiac anomalies or surgical flaws, which contributed to death in 13 cases. Defects in surgery were uncommon but permitted modification in surgical technique to avoid recurrence. Myocardial necrosis and pulmonary foreign body embolism were common findings, the importance of which is uncertain and requires further study for their prevention. Even in the most thoroughly investigated cases postmortem examination has a high yield of clinically important pathology which is undetected during life. .A Russell GA; Berry PJ. .I 201450 .U 90009379 .S J Clin Pathol 9001; 42(9):919-21 .M Adolescence; Adult; Aged; Campylobacter/*IP; Capillaries/PA; Dilatation, Pathologic; Female; Gastric Mucosa/*BS/MI; Gastritis/ET; Human; Hypertension, Portal/CO/MI/*PA; Male; Middle Age. .T Gastric mucosa in patients with portal hypertension: prevalence of capillary dilatation and Campylobacter pylori. .P JOURNAL ARTICLE. .W To determine whether the "congestive" gastropathy associated with portal hypertension showed distinctive histological features independent of inflammatory gastritis, endoscopic biopsy specimens of gastric mucosa from 23 patients with portal hypertension and 25 patients with non-ulcer dyspepsia were examined. Active chronic gastritis associated with Campylobacter pylori was found in three patients with portal hypertension compared with 13 patients with non-ulcer dyspepsia. The changes of reflux gastritis were seen in nine patients with portal hypertension compared with three patients with non-ulcer dyspepsia. Mucosal capillary dilatation, assessed on sections stained for factor VIII related antigen, a specific marker for endothelial cells, was significantly greater in biopsy specimens from patients with portal hypertension but this difference was not apparent on sections stained conventionally. The degree of capillary dilatation was unrelated to the presence of histological gastritis. These observations support the view that portal hypertension is associated with a distinctive gastropathy characterised by prominence and dilatation of mucosal capillaries. .A Foster PN; Wyatt JI; Bullimore DW; Losowsky MS. .I 201451 .U 90009380 .S J Clin Pathol 9001; 42(9):922-6 .M Adult; Aged; Bladder/*PA; Cystitis/*ET/ME/PA; Epithelium/PA; Female; Human; Metaplasia; Middle Age; Receptors, Estrogen/*AN; Support, Non-U.S. Gov't; Vagina/PA. .T Pseudomembranous trigonitis of the bladder: hormonal aetiology. .P JOURNAL ARTICLE. .W Fourteen formalin fixed and paraffin wax embedded biopsy specimens from 10 women (age range 34-68) presenting with pseudomembranous trigonitis were studied using a combination of anti-oestrogen receptor monoclonal antibodies in an avidin-biotin immunoperoxidase technique. All epithelial areas showing vaginal metaplasia exhibited staining confined to the nucleus in the basal and parabasal layers of the squamous epithelium while no staining was encountered in adjacent trigonal transitional epithelium included in nine of the biopsy specimens. The selective expression of nuclear oestrogen receptor in trigonal epithelium affected by vaginal metaplasia in a distribution similar to that reported in vaginal epithelium by other workers lends further support to oestrogen mediated aetiology in this condition and is consistent with an embryological derivation of the trigone, distinct from that of the rest of the bladder. .A Stephenson TJ; Henry L; Harris SC; Giri DD; Fox M; Underwood JC. .I 201452 .U 90009381 .S J Clin Pathol 9001; 42(9):927-30 .M Basement Membrane/AN; Bile Duct Neoplasms/*AN; Bile Ducts/*AN; Cholangioma/*AN; Cholangitis, Sclerosing/*ME; Human; Laminin/*AN; Support, Non-U.S. Gov't. .T Expression of laminin in benign and malignant sclerosing lesions of extrahepatic bile ducts. .P JOURNAL ARTICLE. .W The distribution of laminin, a basement membrane glycoprotein, was studied by an immunohistochemical technique in six samples of benign sclerosing lesions of extrahepatic bile ducts and in 11 sclerosing cholangiocarcinomas. The expression of laminin showed that benign glandular structures were surrounded by a mainly intact basement membrane. In sclerosing cholangiocarcinomas laminin was irregularly distributed, and in large areas totally absent. The findings suggest that deposition of basement membrane material is defective. Sclerosing cholangitis may be extremely difficult to distinguish from well differentiated sclerosing cholangiocarcinoma. This sample was small, but the diseases studied were relatively rare. Staining for laminin might be of additional use to surgical pathologists in the differential diagnosis of benign sclerosing lesions and sclerosing cholangiocarcinomas. .A Haglund C; Roberts PJ; Nordling S. .I 201453 .U 90009382 .S J Clin Pathol 9001; 42(9):931-4 .M Adult; Arterial Occlusive Diseases/*PA; Calcinosis/*PA; Female; Fetal Death; Human; Infant, Newborn; Pregnancy; Umbilical Arteries/*PA. .T Calcification of umbilical artery: two distinct lesions. .P JOURNAL ARTICLE. .W The clinical and pathological features of five cases of calcification of umbilical cord vessels were reviewed. Two distinct lesions were identified: calcification could produce either sclerosis of the wall or obliteration of the lumen. In three cases there was calcification within the media and adventitia of the umbilical arteries, with extension into Wharton's jelly in one case. The pathogenesis of this pattern of calcification--the sclerotic variant--is unclear but the findings of inflammation in the umbilical cord and its vessels, membranes, and decidua suggest intrauterine infection. In two cases there was complete calcification of umbilical arterial lumina resulting in total obliteration. The findings of fetal vessels in the chorionic plate with medial calcification in one of these two cases raises the possibility of thrombosis within the umbilical cord vessels as a cause, but the latter was not found. One infant from each group was liveborn. Both had shown signs of fetal distress in utero and delivered prematurely. The other three pregnancies resulted in macerated stillbirth preterm. .A Khong TY; Dilly SA. .I 201454 .U 90009383 .S J Clin Pathol 9001; 42(9):935-9 .M Enterotoxins; Human; Infant; Kidney Tubules/AN; Staphylococcus aureus/*; Sudden Infant Death/*ET. .T Immunohistological localisation of staphylococcal toxic shock syndrome toxin (TSST-1) antigen in sudden infant death syndrome. .P JOURNAL ARTICLE. .W A polyclonal antiserum to toxic shock syndrome toxin (TSST-1) and a standard immunoperoxidase technique were used on formalin fixed tissues from 50 cases of sudden infant death syndrome (SIDS) to determine if the syndrome was associated with bacterial infection. There was strong specific staining in the renal tubular cells in nine (18%) cases. A similar pattern of staining was seen in three of a series of 50 kidneys selected for comparison from a wide range of necropsy cases. The staining was finely granular within the cytoplasm of proximal convoluted tubular cells and diffuse in tubular cell nuclei. In an attempt to validate the staining pattern the immunoperoxidase technique was also performed on formalin fixed kidneys from rats which had been given intravenous injections of crude bacterial products containing TSST-1. These showed coarse granular cytoplasmic staining in proximal convoluted tubules with some diffuse nuclear staining. This pattern was not seen in controls injected with saline. These results indicate that TSST-1 might have a pathogenic role in some cases of SIDS. .A Newbould MJ; Malam J; McIllmurray JM; Morris JA; Telford DR; Barson AJ. .I 201455 .U 90009385 .S J Clin Pathol 9001; 42(9):944-9 .M Angiolymphoid Hyperplasia with Eosinophilia/*ET/PA; Child, Preschool; Female; Human; Immunization/*AE; Infant; Male; Skin/PA. .T Angiolymphoid hyperplasia with eosinophilia: possible aetiological role for immunisation. .P JOURNAL ARTICLE. .W Five young children (mean age 26.4 months) with angiolymphoid hyperplasia with eosinophilia (Kimura's disease) from either the upper arm or buttock were identified over 18 months. The unusual distribution of the lesions and the young age of the patients suggested a possible association with immunisation. The clinical and histopathological features in these cases were accordingly reviewed. The biopsy specimens showed the usual histological appearances of a prominent inflammatory component, fibrosis, and vascular proliferation associated with aggregates of eosinophils. The features were those of a reactive rather than neoplastic process. Immunohistochemical preparations showed positive staining of variable numbers of plasma cells with antibodies to IgG, IgM, IgA and IgE and a reticular staining of germinal centres with IgM and IgE antibodies. Immunisation histories obtained from the patients' general practitioners showed a remarkable correlation between the distribution of the lesions and the sites of injections and an aetiological role for immunisation in these cases seems likely. .A Hallam LA; Mackinlay GA; Wright AM. .I 201456 .U 90009386 .S J Clin Pathol 9001; 42(9):950-2 .M Adult; Blood Platelet Disorders/*CO; Eosinophilia/*CO; Human; Male; Platelet Activation; Platelet Function Tests; Syndrome. .T Acquired platelet dysfunction with eosinophilia: review of seven adult cases. .P JOURNAL ARTICLE. .W Seven adults with acquired platelet dysfunction with eosinophilia presented with histories of spontaneous bruising and three also had moderate thrombocytopenia. Six patients had platelet function tests performed and all showed variable storage pool defects. When assayed, IgE concentrations were raised. Although only two patients had parasites isolated in their stools, all seven responded to antihelminth treatment. It is speculated that the IgE response to parasites mediates mast cell degranulation, which leads to in vivo platelet activation. .A Lim SH; Tan CE; Agasthian T; Chew LS. .I 201457 .U 90009387 .S J Clin Pathol 9001; 42(9):953-61 .M Antibodies, Monoclonal/*DU; Antigens, Neoplasm/AN; Blotting, Western; Fixatives; Flow Cytometry; Formaldehyde; Human; Leukemia/IM; Lymphoma/IM; Sialoglycoproteins/*AN; Support, Non-U.S. Gov't. .T Molecule detected in formalin fixed tissue by antibodies MT1, DF-T1, and L60 (Leu-22) corresponds to CD43 antigen. .P JOURNAL ARTICLE. .W Three monoclonal antibodies MT1, L60 (Leu-22), and DF-T1, were reported independently as recognising human T cells in routinely processed, paraffin wax embedded tissue. The present study was performed to compare these three reagents in terms of their immunocytochemical reactions and target molecule(s). On Western blotting of white cell extracts the three antibodies reacted with antigens of the same molecular weight (range 110-160 kilodaltons). Furthermore, their immunocytochemical reactivity with normal human cells, as analysed by two-colour flow cytometry, was essentially identical (labelling of monocytes, most T lymphocytes, and weak reactions with some B cells), and the antibodies gave closely similar reactions on 54 white cell derived neoplasms. To identify the target antigen for these three reagents, antibodies from the Third International Workshop on Leucocyte Antigens were reviewed and it was shown that the Western blotting and immunocytochemical reactions of MT1, L60 (Leu-22), and DF-T1 were identical with those of the reagents which defined the CD43 antigen (also known as leucosialin or sialophorin). Furthermore, all these antibodies reacted with cells transfected with a cDNA clone encoding CD43. It is concluded that antibodies MT1, L60 (Leu-22), and DF-T1 all recognise the heavily glycosylated myeloid/lymphoid associated CD43 antigen. .A Stross WP; Warnke RA; Flavell DJ; Flavell SU; Simmons D; Gatter KC; Mason DY. .I 201458 .U 90009388 .S J Clin Pathol 9001; 42(9):962-72 .M Adult; Aged; Aged, 80 and over; Antigens, Neoplasm/AN; Female; Human; Leukemia, B-Cell/IM/*PA; Lymphoma, Non-Hodgkin's/IM/*PA; Male; Middle Age; Tumor Markers, Biological/BL. .T Leukaemic phase of mantle zone (intermediate) lymphoma: its characterisation in 11 cases [see comments] .P JOURNAL ARTICLE. .W Sixteen patients presented with B cell leukaemia (white cell count 26-269 x 10(9)/l) which could not be classified as chronic lymphocytic (CLL), prolymphocytic leukaemia, or follicular lymphoma in leukaemic phase. Eleven patients (10 men, one woman) corresponded histologically to intermediate (INT) or mantle zone lymphoma, and five, with less well defined features, were designated small lymphocytic lymphoma with cleaved cells. The blood films showed a pleomorphic picture with lymphoid cells of predominantly medium size with nuclear irregularities and clefts. The membrane phenotype of the circulating cells showed strong immunoglobulin staining and reactivity with CD5 and FMC7 in all cases tested; CD10 was positive in six out of nine cases. The membrane phenotype of two of the five cases of small lymphocytic lymphoma was close to those of B-CLL and three resembled INT lymphoma. Bone marrow trephine biopsy specimens showed a diffuse pattern of infiltration in INT lymphoma. The median survival of these patients was less than two years, suggesting that a leukaemic presentation is associated with poor prognosis. By combining data from histology, membrane markers, and peripheral blood morphology, the leukaemic phase of typical INT lymphoma can be defined in most cases. .A De Oliveira MS; Jaffe ES; Catovsky D. .I 201459 .U 90009390 .S J Clin Pathol 9001; 42(9):977-81 .M Adult; Female; Globin/*BI; Hemin/PD; Human; Isoniazid/*PD; Male; Middle Age; Reticulocytes/*DE/ME; Support, Non-U.S. Gov't; Thalassemia/*BL. .T Effect of isoniazid, a haem inhibitor, on globin chain synthesis in reticulocytes from non-thalassaemic and beta thalassaemic subjects. .P JOURNAL ARTICLE. .W The effect of isonicotinic acid hydrazide (INH), a potent haem inhibitor, on globin chain synthesis was studied in reticulocytes from the following groups of patients: four non-thalassaemic patients (group i); five beta thalassaemia heterozygotes (group ii); three Hb S/beta thalassaemia heterozygotes (group iii); and two additional patients--one with homozygous beta thalassaemia and the other with thalassaemia intermedia (group iv). This was done to determine whether haem inhibitors depress alpha globin chain synthesis. The progressive increase of INH concentration (10-40 mmol l-1) in reticulocytes from a beta thalassaemia heterozygote resulted in a remarkable decrease of the alpha and beta chain synthesis, ranging from 80% to 97% and from 74% to 96% of control values, respectively, and in a gradual drop of alpha:beta ratio from 1.87 to 1.38. Furthermore, in the samples incubated with 40 mmol l-1 INH, a pronounced inhibition of globin chain synthesis 77 (19%) for alpha chain and 67 (27%) for beta or beta S chain) and a substantial drop of the alpha:beta or beta S ratio in samples with INH (median 1.16) compared with that in samples without INH (median 1.70) were observed. The inhibitory effect of INH was significantly or completely corrected by adding exogenous haem. It is suggested that haem inhibition and the resulting preferential diminution of alpha chain synthesis could provide a new approach to the treatment of homozygous beta thalassaemia with an excess of detrimental free alpha chain in erythroid cells. .A Chalevelakis G; Yalouris AG; Lyberatos C; Economopoulos T; Anastasiou C; Hatziioannou J; Raptis S. .I 201460 .U 90009392 .S J Clin Pathol 9001; 42(9):985-7 .M Antithrombin III/*AN; Enzyme-Linked Immunosorbent Assay/*MT; Human; Support, Non-U.S. Gov't. .T Enzyme linked immunosorbent assay for measuring antithrombin III. .P JOURNAL ARTICLE. .W A competitive ELISA for the measurement of antithrombin III antigen was developed using a pure preparation of antithrombin. This two step immunoassay requires only one antibody binding step and avoids the binding of anti-antithrombin antibody to the solid phase. Plasma samples measured by this ELISA correlated well with measurements taken with immune electrophoresis measurements (r = 0.933); the ELISA was also shown to be both sensitive and precise. .A Edgar P; Jennings I; Harper P. .I 201461 .U 90009393 .S J Clin Pathol 9001; 42(9):988-91 .M DNA Probes/*; DNA Probes, HPV/*; Human; Immunohistochemistry; Nucleic Acid Hybridization; Oligonucleotides/*DU; Papillomaviruses/*IP; Paraffin; Support, Non-U.S. Gov't; Tissue Preservation; Waxes. .T Detection of human papilloma viruses in paraffin wax sections with biotinylated synthetic oligonucleotide probes and immunogold staining. .P JOURNAL ARTICLE. .W Human papilloma virus was detected by in situ hybridisation in routinely processed paraffin wax sections using a synthetically produced oligonucleotide probe, end-labelled with biotin, and amplified with anti-biotin-immunogold silver staining (anti-biotin-IGSS). This system proved more sensitive than amplification with streptavidin-biotinylated alkaline phosphatase for detecting human papilloma virus type 16 in cervical tissues. The method was successfully combined with antigen staining for papilloma virus common antigens in skin and genital warts. This simple and quick method, using non-radioactively labelled synthetic probes, may be useful for the detection of other viruses in stored material and may be suitable for other double staining procedures. .A Cubie HA; Norval M. .I 201462 .U 90009394 .S J Clin Pathol 9001; 42(9):992-4 .M Human; Nucleolus Organizer Region/*PA; Paraffin; Silver Nitrate/*; Stains and Staining/*MT; Tissue Preservation; Waxes. .T Improved silver technique for showing nucleolar organiser regions in paraffin wax sections. .P JOURNAL ARTICLE. .W An improved technique for the demonstration of nucleolar organiser regions (NORs) was devised. It has the advantage that any non-specific background deposits which mimic the NOR dots formed during staining are trapped by the celloidin film. The specificity of the silver staining is also increased by the postfixation treatment of sections in an acetic acid-ethanol mixture. Moreover, it is economical because of the low silver content and small volume of the incubation solution used. .A Chiu KY; Loke SL; Wong KK. .I 201463 .U 90009395 .S J Clin Pathol 9001; 42(9):995-1000 .M Campylobacter/*IP; DNA Probes/*; DNA, Bacterial/AN; Female; Gastric Mucosa/*MI; Human; Middle Age; Nucleic Acid Hybridization/*. .T Detection of Campylobacter pylori in stomach tissue by DNA in situ hybridisation. .P JOURNAL ARTICLE. .W A non-radioactive DNA in situ hybridisation (DISH) protocol was developed. It requires the use of biotinylated Campylobacter pylori DNA as the probe to detect C pylori DNA in routinely embedded stomach biopsy specimens. In sequential tissue samples from a 58 year old woman with recurrent chronic active gastritis the C pylori probe hybridised with bacteria whenever they were histologically visible. When no bacteria were visible histologically, hybridisation was negative with one exception. In a single biopsy specimen without visible C pylori, hybridisation occurred with the surface of the antrum epithelium, while control hybridisation with a heterologous probe remained negative. From a parallel biopsy specimen taken at the same time the C pylori culture was positive. It is concluded that DISH, although more laborious than routine staining techniques, may be more sensitive in that it detects bacteria very easily, even when sections are not counterstained or when they are present in low numbers, and that bacteria which do hybridise are unequivocally identified as C pylori and not Campylobacter-like organisms. .A Van den Berg FM; Zijlmans H; Langenberg W; Rauws E; Schipper M. .I 201464 .U 90009613 .S J Dermatol Surg Oncol 9001; 15(10):1048 .M Human; Hydrogen-Ion Concentration; Lidocaine/*AD; Skin/*SU. .T Neutralized lidocaine [editorial] .P EDITORIAL. .A Skouge JW. .I 201465 .U 90009614 .S J Dermatol Surg Oncol 9001; 15(10):1050-3 .M Electrocoagulation/*MT; Hemostasis, Surgical/IS/*MT; Human; Sterilization. .T Blood vessel coagulation for incisional surgery [see comments] .P JOURNAL ARTICLE. .W Blood vessel electrocoagulation allows the cutaneous surgeon rapid and reliable bleeder control for incisional wounds. The following article discusses the various instruments and techniques used for blood vessel electrocoagulation. .A Sebben JE. .I 201466 .U 90009615 .S J Dermatol Surg Oncol 9001; 15(10):1055-9 .M Case Report; Facial Neoplasms/*SU; Female; Hamartoma Syndrome, Multiple/*SU; Human; Laser Surgery/*; Middle Age; Neoplasms, Multiple Primary/*SU. .T Cowden's disease--treatment of cutaneous lesions using carbon dioxide laser vaporization: a comparison of conventional and superpulsed techniques. .P JOURNAL ARTICLE. .W Cowden's disease is a genodermatosis associated with both cutaneous and visceral manifestations, including cancer. Trichilemmomas represent one of the benign cutaneous lesions associated with this syndrome and may be responsible for significant cosmetic disfigurement. Using the carbon dioxide (CO2) laser in its vaporizational mode of operation, a patient with multiple trichilemmomas of the nose, previously unsuccessfully treated with multiple medical and surgical procedures, obtained excellent cosmetic results. .A Wheeland RG; McGillis ST. .I 201467 .U 90009618 .S J Dermatol Surg Oncol 9001; 15(10):1072-3 .M Adipose Tissue/*TR; Human; Surgery, Plastic/*MT. .T Fat transfer--a "pinch" technique for accurate placement of donor tissue. .P JOURNAL ARTICLE. .W A useful and simple technique for fat transfer requiring bilateral pressure prior to injection for effective correction of cosmetic defects is described. .A Bisaccia E; Scarborough DA; Swensen RD. .I 201468 .U 90009619 .S J Dermatol Surg Oncol 9001; 15(10):1077-80 .M Biopsy/*MT; Hemorrhage/ET; Human; Mouth Diseases/*PA; Paresthesia/ET; Postoperative Complications; Surgical Wound Dehiscence/ET; Surgical Wound Infection/ET. .T How to biopsy oral lesions. .P JOURNAL ARTICLE. .W Biopsy of oral lesions is a procedure of considerable diagnostic value. The size, location, and characteristics of the lesion determine the type of procedure used. The procedure is explained using photographs and appropriate commentary. .A Harahap M. .I 201469 .U 90009620 .S J Dermatol Surg Oncol 9001; 15(10):1081-3 .M Adult; Aged; Aged, 80 and over; Anesthesia, Local/*MT; Double-Blind Method; Drug Stability; Human; Hydrogen-Ion Concentration; Lidocaine/*AD; Middle Age. .T Neutralized lidocaine with epinephrine for local anesthesia. .P JOURNAL ARTICLE. .W The pain of infiltrating lidocaine with epinephrine into skin is reduced by the addition of sodium bicarbonate. The effect of varied concentrations of sodium bicarbonate on pain of infiltration of 1% lidocaine with epinephrine 1:100,000 was measured. Sodium bicarbonate at 40 and 100 meq/L of anesthetic solution caused significantly less pain than did 0 or 10 meq/L. The stability of epinephrine in a solution at pH 7.3 was also determined. Epinephrine concentration declined approximately 25% per week in anesthetic solution containing 100 meq/L sodium bicarbonate. .A Stewart JH; Cole GW; Klein JA. .I 201470 .U 90009621 .S J Dermatol Surg Oncol 9001; 15(10):1089-90 .M Animal; Guinea Pigs; Injections, Intradermal; Skin/PA; Tannic Acid/*AD; Tannins/*AD; Tattooing/*. .T Tattoo removal by overtattooing with tannic acid. .P JOURNAL ARTICLE. .W Removal of tattoos was studied in the guinea pig. Professional tattoos were made, and two different solutions of tannic acid were injected intradermally into the tattoos four times. The macroscopic end result was formation of a slight fibrosis with little visible pigment. Histologic examination after treatment showed a moderate fibrosis with little visible pigment situated deeper in the dermis than in the untreated tattoo. .A Fogh H; Wulf HC; Poulsen T; Larsen P. .I 201471 .U 90009622 .S J Dermatol Surg Oncol 9001; 15(10):1092-8 .M Adult; Axilla; Female; Fingers; Forehead; Hand; Human; Leg; Lip; Male; Middle Age; Skin Pigmentation; Support, Non-U.S. Gov't; Tattooing/AE/IS/*MT; Vitiligo/*TH. .T Micropigmentation for the treatment of vitiligo. .P JOURNAL ARTICLE. .W A technique of permanent dermal micropigmentation using a nonallergenic iron oxide pigment to cover recalcitrant areas of vitiligo is described. The areas included in this study were the distal digits, the lips, hands, wrists, axillae, elbows, hairline, perioral area, and lower legs. The immediate postmicropigmentation results invariably showed dramatic aesthetic improvements. There was a moderate degree of fading in the majority of cases, most of which occurred within the first six weeks. The pigment that remained usually persisted with minimal to no further fading. Short- and long-term complications, which were few, mild, and resolved fully, are discussed. No allergic reactions to the pigment or koebnerization of the vitiligo have been noted. .A Halder RM; Pham HN; Breadon JY; Johnson BA. .I 201472 .U 90009623 .S J Dermatol Surg Oncol 9001; 15(10):1101-6 .M Dissection; Head/*AH/BS/IR; Human; Neck/*AH/BS/IR. .T Key anatomic structures of the face and neck for the dermatologic surgeon: their relationship in a cadaver dissection. .P JOURNAL ARTICLE. .W A working knowledge of vital anatomic structures of the face and neck are imperative for the dermatologic surgeon. This article correlates those commonly encountered structures with a cadaver dissection as they relate to skin cancer excision, rhytidectomies, and liposuction. .A Phillips JH 3d; Walker LB; Millikan LE. .I 201473 .U 90009624 .S J Dermatol Surg Oncol 9001; 15(10):1108-12 .M Alopecia/*SU; Human; Methods; Scalp/*SU. .T A new technique for curvilinear scalp reduction. .P JOURNAL ARTICLE. .W A technique of alopecia reduction utilizing a curvilinear ellipse employing a sequential excision and suture technique is described. Advantages of the technique over previously described procedures are presented. Measurements of individual scalp elasticity and alternating suture tension vectors help to produce an excellent cosmetic result with minimal complications. .A Hitzig GS; Sadick NS. .I 201474 .U 90009626 .S J Dermatol Surg Oncol 9001; 15(10):1124 .M Carcinoma, Basal Cell/*SU; Carcinoma, Squamous Cell/*SU; Eyelid Neoplasms/*SU; Human; Neoplasm Recurrence, Local; Surgical Flaps/*. .T Reconstruction of the medical canthal area [letter; comment] .P COMMENT; LETTER. .A Rodriguez-Sains RS. .I 201475 .U 90009627 .S J Dermatol Surg Oncol 9001; 15(10):1124-5 .M Aged; Carcinoma, Basal Cell/PA/*SU; Carcinoma, Squamous Cell/PA/*SU; Case Report; Female; Human; Malpractice/*; Neoplasm Recurrence, Local/*; Skin Neoplasms/PA/*SU. .T False-negative margins [letter] .P LETTER. .A Zimmerman MC. .I 201476 .U 90009628 .S J Dermatol Surg Oncol 9001; 15(10):1125-6 .M Anastomosis, Surgical; Face/*SU; Human; Lip; Surgical Flaps/*MT. .T Peri-alar rim flap movements [letter; comment] .P COMMENT; LETTER. .A Field LM. .I 201477 .U 90009715 .S J Am Dent Assoc 9001; 119(4):523-5 .M Adult; Case Report; Dental Pulp Calcification/*CI/RA; Dentinogenesis; Female; Follow-Up Studies; Human; Lupus Erythematosus, Systemic/*DT; Periodontitis/TH; Prednisolone/*AE. .T Root canal calcification associated with prednisone therapy: a case report. .P JOURNAL ARTICLE. .W This report details an 8-year follow-up of a patient with systemic lupus erythematosus (SLE) who was treated with up to 60 mg per day of prednisone for more than 8 years. Radiographic documentation demonstrated complete calcification of all pulp chambers and root canals during an 8-year period. During this time, the patient had been successfully treated for case type III adult onset periodontitis. Follow-up examinations recorded minimal attachment loss, and radiographs showed stable bone levels. .A Gold SI. .I 201478 .U 90009716 .S J Am Dent Assoc 9001; 119(4):527-30 .M Adult; Arthrography; Dislocations/*DI/PA; Female; Human; Magnetic Resonance Imaging/*; Temporomandibular Joint Syndrome/*DI/PA/RA. .T Diagnosing disk dysfunction and tissue changes in the temporomandibular joint with magnetic resonance imaging. .P JOURNAL ARTICLE. .W Magnetic resonance imaging (MRI) is a noninvasive technique that clearly documents disk positioning abnormalities and tissue structure changes not previously discovered except by surgical intervention and biopsy. The MRI also shows hyperplasias, disk folds, displaced disks, and disk thinning-important information to have before surgical intervention is begun. Overall, MRI provides a basis for complex dental treatment planning and prognostic evaluation. .A Kirk WS Jr. .I 201479 .U 90009719 .S J Am Dent Assoc 9001; 119(4):543-4 .M Aged; Carcinoma, Squamous Cell/*/PA; Case Report; Erythroplasia/*ET; Gingival Neoplasms/*/PA; Human; Male; Support, Non-U.S. Gov't. .T Erythroplastic lesion on the mandibular marginal gingiva. .P JOURNAL ARTICLE. .W Carcinoma of the gingiva is a significant risk to patients because the asymptomatic characteristics of erythroplastic lesions are not always readily identified. This case report shows the similarity in clinical appearance of squamous cell carcinoma of the gingiva to the common inflammatory changes associated with periodontal disease. A similar clinical presentation might be seen in any lesion with increased vascularity, including Kaposi's sarcoma associated with human immunodeficiency virus infection. Any erythroplastic change involving the oral mucosa should be viewed with suspicion and, if not resolved after removal of local sources of irritation, must be biopsied to establish a definitive diagnosis. .A Craig RM Jr; Vickers VA; Correll RW. .I 201480 .U 90009720 .S J Am Coll Cardiol 9001; 14(4):1003-44 .M Coronary Disease/*EC; Employment/*; Human; Insurance, Health/*; United States. .T 20th Bethesda Conference: Insurability and employability of the patient with ischemic heart disease. October 3-4, 1988, Bethsda, Maryland. .P JOURNAL ARTICLE. .I 201481 .U 90009721 .S J Am Coll Cardiol 9001; 14(4):1010-5 .M Coronary Disease/*EC; Disability Evaluation; Employment/*; Government; Human; Industry; Insurance, Health/*; United States; Workmen's Compensation. .T Committee report on economic, administrative and legal factors influencing the insurability and employability of patients with ischemic heart disease. .P JOURNAL ARTICLE. .A Guillette W; Judge RD; Koehn E; Miller JE; Palmer RK; Tremblay JL. .I 201482 .U 90009722 .S J Am Coll Cardiol 9001; 14(4):1016-25 .M Coronary Disease/EC/*MO; Disability Evaluation; Employment; Human; Insurance, Health; Occupations; Prognosis/*; Risk Factors; United States. .T Task Force I: Determination of prognosis in patients with ischemic heart disease. .P JOURNAL ARTICLE. .A Pryor DB; Bruce RA; Chaitman BR; Fisher L; Gajewski J; Hammermeister KE; Pauker SG; Stokes J 3d. .I 201483 .U 90009723 .S J Am Coll Cardiol 9001; 14(4):1025-34 .M Coronary Disease/DI/*EC; Disability Evaluation/*; Employment; Human; Insurance, Health; Occupations; United States; Work Schedule Tolerance. .T Task Force II: Determination of occupational working capacity in patients with ischemic heart disease. .P JOURNAL ARTICLE. .A Haskell WL; Brachfeld N; Bruce RA; Davis PO; Dennis CA; Fox SM 3d; Hanson P; Leon AS. .I 201484 .U 90009724 .S J Am Coll Cardiol 9001; 14(4):1034-42 .M Adaptation, Psychological; Attitude to Health; Behavior Therapy; Coronary Disease/EC/*PX; Employment; Human; Insurance, Health; Patient Acceptance of Health Care; Physician-Patient Relations; Sick Role; Support, U.S. Gov't, P.H.S.; United States. .T Task Force III: Assessment of psychological status in patients with ischemic heart disease. .P JOURNAL ARTICLE. .A Blumenthal JA; Bradley W; Dimsdale JE; Kasl SV; Powell LH; Taylor CB. .I 201485 .U 90009725 .S J Am Coll Cardiol 9001; 14(4):1045-50 .M Angioplasty, Transluminal, Percutaneous Coronary/*IS; Animal; Coronary Circulation; Coronary Disease/*PC; Coronary Vessels/PH; Dogs; Electrocardiography; Female; Male; Myocardium/*PA; Necrosis; Support, Non-U.S. Gov't; Time Factors. .T The autoperfusion balloon angioplasty catheter limits myocardial ischemia and necrosis during prolonged balloon inflation. .P JOURNAL ARTICLE. .W A new balloon angioplasty catheter with multiple proximal and distal side holes has previously been shown to allow significant protection from ischemia during a 3 min balloon inflation in a coronary artery. Because of the potential benefits of very long periods of inflation, 21 anesthetized thoracotomized dogs were randomized to left circumflex coronary artery occlusion with either a standard or an autoperfusion balloon catheter for 90 min. Nine dogs sustained ventricular fibrillation before completing the study, eight after standard balloon inflation and one after autoperfusion balloon inflation (p = 0.04). ST segment elevation was 0.45 +/- 0.13 mV after 15 min of standard balloon inflation versus -0.03 +/- 0.03 mV after autoperfusion balloon inflation (p less than 0.001). Regional myocardial blood flow was 0.02 +/- 0.01 ml/min per g after 30 min of standard balloon inflation compared with 0.78 +/- 0.23 ml/min per g in the group subjected to autoperfusion balloon inflation (p = 0.01). The area of necrosis/area at risk in the standard catheter group was 40.4 +/- 19.3% versus 1.2 +/- 1.2% for the autoperfusion catheter group (p = 0.01). Thus, the autoperfusion catheter preserves blood flow and limits myocardial ischemia and necrosis despite 90 min of balloon inflation. .A Campbell CA; Rezkalla S; Kloner RA; Turi ZG. .I 201486 .U 90009726 .S J Am Coll Cardiol 9001; 14(4):1051-2 .M Angioplasty, Transluminal, Percutaneous Coronary/*IS; Animal; Coronary Circulation; Coronary Disease/PC; Coronary Vessels/PH; Dogs; Human; Myocardium/PA; Necrosis. .T Is the leaking balloon angioplasty catheter a better catheter? [editorial] .P EDITORIAL. .A Bourassa MG. .I 201487 .U 90009727 .S J Am Coll Cardiol 9001; 14(4):1053-66 .M Action Potentials/DE; Animal; Comparative Study; Dogs; Electric Stimulation; Electrocardiography/*; Endocardium/*PH; Heart Conduction System/*PH; Heart Rate/*; Male; Papillary Muscles/PH; Pericardium/*PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Time Factors; 4-Aminopyridine/PD. .T Rate dependence of action potential duration and refractoriness in canine ventricular endocardium differs from that of epicardium: role of the transient outward current. .P JOURNAL ARTICLE. .W Previous studies have provided evidence for an important contribution of the transient outward current to the electrical activity of canine ventricular epicardium, but not endocardium. The present study examines the characteristics of action potential duration and refractoriness in these two tissue types. The time and rate dependence of changes in action potential duration and refractoriness observed in epicardium were significantly more accentuated than in endocardium. The restitution of action potential duration in epicardium paralleled the restitution of phase 1 amplitude of the action potential in this tissue. The correlation between phase 1 amplitude and action potential duration recorded from a large number of epicardial and endocardial preparations was significant under both steady state and restitution conditions. 4-Aminopyridine, a transient outward current blocker, decreased the time dependence of phase 1 amplitude and concomitantly decreased the time dependence of action potential duration in epicardium. 4-Aminopyridine abbreviated the action potential duration of epicardium at slow stimulation rates but had little effect or prolonged it at fast rates or after premature stimulation. (The availability of a transient outward current is relatively small after premature stimulation.) The data support the hypothesis that the prominent presence of a transient outward current in epicardium, but not endocardium, contributes to the differences in the time and rate dependence of action potential duration and refractoriness in the two tissue types. The results also demonstrate the effect of an outward current to prolong the action potential and the effect of an outward current blocker to abbreviate the action potential.(ABSTRACT TRUNCATED AT 250 WORDS) .A Litovsky SH; Antzelevitch C. .I 201488 .U 90009728 .S J Am Coll Cardiol 9001; 14(4):1067-73 .M Animal; Constriction, Pathologic/DT; Coronary Circulation; Coronary Disease/BL/*DT; Creatine Kinase Isoenzymes/*BL; Dogs; Myocardial Reperfusion/*; Support, U.S. Gov't, P.H.S.; Thrombolytic Therapy/*. .T Optimal criteria for rapid detection of myocardial reperfusion by creatine kinase MM isoforms in the presence of residual high grade coronary stenosis. .P JOURNAL ARTICLE. .W Analysis of isoforms of MM creatine kinase (CK) in plasma is being developed as a means for rapid detection of coronary recanalization in patients given thrombolytic agents. To determine whether flow-limiting residual stenosis typical of that seen in patients affects plasma isoform profiles, stenosis sufficient to preclude reactive hyperemia was induced in dogs before coronary occlusion, followed by recanalization in 2 h. Plasma activities of the MM CK isoform released from myocardium (MM3) and its two conversion products elaborated sequentially (MM2 and MM1) were assayed in serial samples with a rapid quantitative chromatofocusing procedure. Reperfusion in 10 dogs shortened the mean intervals (+/-SD) to the occurrence of peak MM3 activity (3.7 +/- 0.9 h), peak MM3 expressed as a percent of total CK activity (MM3%, 2.5 +/- 0.3 h) and the maximal ratio of MM3 to MM1 (2.7 +/- 0.3 h) compared with results in 10 control dogs without reperfusion. Nevertheless, the appearance of these peaks was delayed by 8% to 57% when residual stenosis was present. In contrast, the rate of increase of MM3% was delineated before the peak, was fivefold greater with recanalization (1.19 +/- 0.46 versus 0.26 +/- 0.11% min-1 in control dogs) and was not attenuated by residual stenosis. Thus, this criterion appears capable of delineating recanalization early after thrombolysis whether or not high grade residual stenosis is present. .A Nohara R; Myears DW; Sobel BE; Abendschein DR. .I 201489 .U 90009729 .S J Am Coll Cardiol 9001; 14(4):1074-83 .M Animal; Cardiac Pacing, Artificial/*; Cardiac Tamponade/*DI; Comparative Study; Dogs; Electrocardiography/*; Female; Male; Needles; Pericardial Effusion/*DI; Pericardium; Punctures/*MT; Support, U.S. Gov't, P.H.S.. .T Pericardiocentesis guided by a pulse generator. .P JOURNAL ARTICLE. .W This study was performed to compare pericardiocentesis guided by a pacing current applied through the pericardiocentesis needle with the traditional method of monitoring ST segment elevation from the needle tip electrogram. ST segment elevation was measured at 3 mm from the epicardium, after epicardial contact, after epicardial penetration and again at 3 mm from the epicardium after epicardial penetration. Two millivolts of ST segment elevation gave the highest combined positive (86%) and negative (79%) predictive value for epicardial contact by the pericardiocentesis needle between the two groups with the largest difference: 3 mm from the epicardium before contact and after epicardial penetration. Therefore, ST segment monitoring cannot reliably determine the point of epicardial contact. To determine the optimal stimulus strength for pulse generator-guided pericardiocentesis, pacing studies were performed using 2, 4, 6, 8 and 10 mA unipolar stimulus strengths. The pacing studies were performed both with and without a hemodynamically significant pericardial effusion to determine if increased pericardial pressure altered the pacing threshold. A 4 mA unipolar cathodal stimulus was chosen because it captured the ventricle only with direct contact of the epicardium. Ten dogs were instrumented and cardiac tamponade produced so that a subxiphoid approach to the epicardium with the pacing needle electrode could be attempted. During pericardiocentesis, needle tip electrograms were recorded, alternating with pacing attempts using a 4 mA unipolar stimulus. In all 10 dogs, the effusion was entered and epicardium was contacted as indicated by capture. No myocardial perforation or coronary artery or venous injuries were produced. These findings support the use of a pulse generator to guide pericardiocentesis. .A Tweddell JS; Zimmerman AN; Stone CM; Rokkas CK; Schuessler RB; Boineau JP; Cox JL. .I 201490 .U 90009731 .S J Am Coll Cardiol 9001; 14(4):1093-6 .M Animal; Arrhythmia/*ET; Electrocardiography; Heart Conduction System/PP; Human; Magnesium/BL/*PH; Magnesium Deficiency/*CO; Potassium Channels/ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Is hypomagnesemia or magnesium deficiency arrhythmogenic? .P JOURNAL ARTICLE. .A Surawicz B. .I 201491 .U 90009732 .S J Am Coll Cardiol 9001; 14(4):1100-24 .M Cardiology/*ED; Fellowships and Scholarships; Human; Internship and Residency/*; Thoracic Surgery/*ED; United States. .T Training programs in the United States in adult cardiology, pediatric cardiology and cardiothoracic surgery. .P JOURNAL ARTICLE. .I 201492 .U 90009733 .S J Am Coll Cardiol 9001; 14(4):1125 .M Angioplasty, Transluminal/*; Angioplasty, Transluminal, Percutaneous Coronary/*; Arterial Occlusive Diseases/*TH; Human; Recurrence. .T The spoof factor [letter] .P LETTER. .A Diethrich EB. .I 201493 .U 90009738 .S J Am Coll Cardiol 9001; 14(4):874-6 .M Contrast Media; Heart/*RI; Human; Myocardial Infarction/DT/*RI; Myocardial Reperfusion/*; Nitriles; Organotechnetium Compounds; Thallium Radioisotopes/DU; Thrombolytic Therapy/*. .T Noninvasive assessment of myocardial salvage after coronary reperfusion: a perpetual quest of nuclear cardiology [editorial] .P EDITORIAL. .A Beller GA. .I 201494 .U 90009740 .S J Am Coll Cardiol 9001; 14(4):885-92 .M Adult; Coronary Disease/*DI/MO; Electrocardiography/*; Exercise Test; Exertion/*; Female; Follow-Up Studies; Heart Catheterization; Human; Male; Middle Age; Prognosis; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Survival Rate; Time Factors. .T Painless exercise ST deviation on the treadmill: long-term prognosis. .P JOURNAL ARTICLE. .W To evaluate the clinical correlates and long-term prognostic significance of silent ischemia during exercise, 1,698 consecutive symptomatic patients with coronary artery disease who had both treadmill testing and cardiac catheterization were studied. These patients were classified into three groups: Group 1 = patients with no exercise ST deviation (n = 856), Group 2 = patients with painless exercise ST deviation (n = 242) and Group 3 = patients with both angina and ST segment deviation during exercise (n = 600). Patients with exercise angina had a history of a longer and more aggressive anginal course (with a greater frequency of angina, with nocturnal episodes and/or progressive symptom pattern) and more severe coronary artery disease (almost two-thirds had three vessel disease). The 5 year survival rate among the patients with painless ST deviation was similar to that of patients without ST deviation (86% and 88%, respectively) and was significantly better than that of patients with both symptoms and ST deviation (5 year survival rate 73% in patients with exercise-limiting angina). Similar trends were obtained in subgroups defined by the amount of coronary artery disease present. In the total study group of 1,698 patients, silent ischemia on the treadmill was not a benign finding (average annual mortality rate 2.8%) but, compared with symptomatic ischemia, did indicate a subgroup of patients with coronary artery disease who had a less aggressive anginal course, less coronary artery disease and a better prognosis. Thus, silent ischemia during exercise testing in patients with symptomatic coronary artery disease represents an intermediate risk response in the spectrum of exercise-induced ischemia. .A Mark DB; Hlatky MA; Califf RM; Morris JJ Jr; Sisson SD; McCants CB; Lee KL; Harrell FE Jr; Pryor DB. .I 201495 .U 90009741 .S J Am Coll Cardiol 9001; 14(4):893-4 .M Coronary Disease/*DI/MO; Electrocardiography; Exercise Test; Exertion/*; Human; Prognosis. .T Prognosis in exercise-induced silent ischemia: is there a consensus? [editorial] .P EDITORIAL. .A Cohn PF. .I 201496 .U 90009742 .S J Am Coll Cardiol 9001; 14(4):895-900 .M Angina Pectoris/RI; Comparative Study; Coronary Disease/*RI; Coronary Vessels/RA; Electrocardiography; Exercise Test; Exertion/*; Female; Heart/*RI; Human; Male; Middle Age; Tomography, Emission-Computed, Single-Photon/*. .T Silent ischemia: evaluation by exercise and redistribution tomographic thallium-201 myocardial imaging. .P JOURNAL ARTICLE. .W To compare the amount of myocardium jeopardized during silent ischemia and painful ischemia, 112 consecutive patients undergoing coronary arteriography with ischemia demonstrated by exercise and redistribution tomographic thallium-201 myocardial imaging (SPECT) were divided into two groups: 84 patients without anginal pain (silent ischemia) and 28 with pain (painful ischemia). The SPECT apical, mid and basal ventricular levels of the short-axis view and the apical portion of the long-axis view were divided into 20 segments. The results were 1) 7.4 +/- 4.7 ischemic segments in silent ischemia and 7.6 +/- 3.7 in painful ischemia (p = NS) with 4.7 +/- 3.6 segments in silent ischemia undergoing total redistribution compared with 5.4 +/- 3.4 in painful ischemia (p = NS); 2) no difference in the incidence of single, double or triple vessel disease between silent and painful ischemic groups; 3) similar anatomic distribution of ischemic segments between the two groups; 4) more positive exercise electrocardiographic (ECG) changes in painful ischemia (70%) than in silent ischemia (32%) (p less than 0.001) with equal amounts of ischemia associated with positive and negative exercise ECG findings. Conclusions: 1) Patients with silent and painful ischemia during exercise have similar amounts of ischemic myocardium demonstrated by tomographic thallium-201 imaging and similar extent of angiographically documented coronary artery disease despite the absence of pain and the lower incidence of positive exercise ECG findings in silent ischemia. 2) Positive and negative exercise ECG findings were associated with similar amounts of ischemic myocardium. .A Hecht HS; Shaw RE; Bruce T; Myler RK. .I 201497 .U 90009743 .S J Am Coll Cardiol 9001; 14(4):901-2 .M Coronary Disease/*/RI; Exercise Test; Heart/RI; Human; Nomenclature/*; Tomography, Emission-Computed, Single-Photon. .T "Silent ischemia": what is it? [editorial] .P EDITORIAL. .A Pohost GM. .I 201498 .U 90009744 .S J Am Coll Cardiol 9001; 14(4):903-11 .M Anticoagulants/TU; Echocardiography; Female; Follow-Up Studies; Heart Diseases/DI/DT/*ET; Human; Male; Middle Age; Myocardial Infarction/*CO; Prospective Studies; Thrombosis/DI/DT/*ET; Time Factors. .T The natural history of left ventricular thrombus in myocardial infarction: a rationale in support of masterly inactivity [see comments] .P JOURNAL ARTICLE. .W One hundred five unselected and consecutive patients were prospectively studies after acute transmural myocardial infarction to assess the incidence of mural thrombus formation and to relate the presence of thrombus to patient outcome in terms of systemic embolic events, functional class and survival. In 87 patients, optimal quality two-dimensional echocardiographic studies were obtained and were repeated at daily intervals to detect mural thrombus formation. The site of infarction was anterior in 53 patients and inferior in 34. On admission, all patients received subcutaneous heparin and antiplatelet agents (aspirin, dipyridamole); none received full anticoagulant therapy. Left ventricular mural thrombus was visualized between 2 and 11 days (median 6) after the clinical onset of infarction in 21 (40%) of the 53 patients with anterior infarction. No patients with inferior infarction had echocardiographic evidence of thrombus formation. During follow-up of 22 to 51 months (mean 39), none of the 21 patients with mural thrombus had clinical evidence of systemic embolism. One patient with inferior and one with anterior infarction had a cerebral embolus 7 days and 9 months, respectively, after the acute event, but neither of these patients had echocardiographic evidence of left ventricular thrombus at any stage. Echocardiography performed at 1 and 2 years of follow-up showed persistent evidence of thrombus in only 8 (31%) and 5 (24%) of the 21 patients, respectively. On admission, the functional class of patients with anterior myocardial infarction and thrombus was similar to that of patients without ventricular thrombus.(ABSTRACT TRUNCATED AT 250 WORDS) .A Nihoyannopoulos P; Smith GC; Maseri A; Foale RA. .I 201499 .U 90009745 .S J Am Coll Cardiol 9001; 14(4):912-4 .M Cerebrovascular Disorders/*ET/PC; Fibrinolytic Agents/*TU; Heart Diseases/*ET/PC; Human; Myocardial Infarction/*CO; Thrombosis/*ET/PC. .T Left ventricular thrombus and stroke after myocardial infarction: toward prevention or perplexity? [editorial] .P EDITORIAL. .A Halperin JL; Fuster V. .I 201500 .U 90009746 .S J Am Coll Cardiol 9001; 14(4):915-20 .M Adult; Biopsy/ST; Female; Human; Male; Myocarditis/*PA; Myocardium/*PA. .T Insensitivity of right ventricular endomyocardial biopsy in the diagnosis of myocarditis. .P JOURNAL ARTICLE. .W The clinical suspicion of myocarditis relies strongly on endomyocardial biopsy for confirmation, yet the sensitivity of the procedure in this setting has not been clearly defined. Biopsy sensitivity was determined in 14 hearts with histologically proved myocarditis studied ex vivo, including 12 autopsy hearts and 2 native hearts explanted at cardiac transplantation. With use of the Stanford and Cordis bioptomes, endoymocardial biopsy was performed near the apex on the right side of the ventricular septum (four to five samples/bioptome per patient) and repeated in the nonapical portion of the septum from the moderator band to the subpulmonary infundibulum (additional three to five samples/bioptome per patient). In a casewise assessment, 43% to 57% of the endomyocardial samples were diagnostic for myocarditis, as calculated separately for each bioptome in each region of sampling (apical/nonapical). Both apical and nonapical sensitivity improved to 64% when the findings of the two bioptomes were combined (eight to nine samples/patient in each region). By collectively analyzing all available samples for each patient, 11 (79%) of 14 cases could be diagnosed, but this required a mean of 17.2 samples/patient, a number clinically unrealistic. The exclusion of four cases of fungal myocarditis from analysis did not significantly alter the results. In transmural ventricular sections, none of four patients with sudden death had inflammatory disease confined to the conduction system. In conclusion, despite six to eight negative biopsy samples/patient with suspected myocarditis, repeat biopsy may still be warranted. .A Chow LH; Radio SJ; Sears TD; McManus BM. .I 201501 .U 90009747 .S J Am Coll Cardiol 9001; 14(4):921-2 .M Biopsy/ST; Human; Myocarditis/*PA; Myocardium/*PA. .T Acute myocarditis: is sampling error a contraindication for diagnostic biopsies? [editorial] .P EDITORIAL. .A Billingham ME. .I 201502 .U 90009748 .S J Am Coll Cardiol 9001; 14(4):923-8 .M Adult; Aged; Coronary Disease/*DI; Echocardiography/*; Exercise Test/*; Human; Male; Middle Age; Myocardial Infarction; Reproducibility of Results; Stroke Volume; Support, U.S. Gov't, P.H.S.. .T Reproducibility of two-dimensional exercise echocardiography. .P JOURNAL ARTICLE. .W To determine the reproducibility of two-dimensional exercise echocardiography, duplicate studies were performed on the same patients a median of 14 days apart. Because measurements are operator-dependent, interobserver variability was calculated for two experienced readers who interpreted the findings independently in a blinded manner. A high degree of interobserver agreement was found in evaluation of both ejection fraction measurements and wall motion abnormalities. Readings for ejection fraction immediately after exercise taken on different days could be estimated within 4% of the values measured in the first test; similarly measured wall motion score index was within 6% of that in the first test. Ejection fractions and wall motion scores were highly correlated between tests 1 and 2. The correlation coefficients between tests 1 and 2 were 0.92 for both the pre- and postexercise ejection fractions and 0.98 for both the pre- and postexercise wall motion scores. Quantitative two-dimensional echocardiography immediately after exercise is highly reproducible, providing a valuable tool for assessing serial changes in left ventricular function. .A Oberman A; Fan PH; Nanda NC; Lee JY; Huster WJ; Sulentic JA; Storey OF. .I 201503 .U 90009749 .S J Am Coll Cardiol 9001; 14(4):929-35 .M Adult; Aorta/PH; Blood Flow Velocity; Cardiac Pacing, Artificial; Coronary Circulation; Echocardiography, Doppler/*; Electrocardiography; Heart Rate/*; Human; Male; Myocardial Contraction/*; Posture. .T Effect of heart rate on Doppler indexes of systolic function in humans. .P JOURNAL ARTICLE. .W Recent investigations have shown Doppler echocardiography to be useful in the noninvasive assessment of left ventricular systolic function. No data exist, however, regarding the influence of heart rate on Doppler measurements of aortic blood flow velocity and acceleration in humans. Thus, 12 normal volunteers underwent continuous wave Doppler ultrasound recording from the suprasternal notch at baseline and during progressive transesophageal atrial pacing at intervals of 10 beats/min between 90 and 140 beats/min while 100% atrial capture and 1:1 atrioventricular conduction were maintained. Subjects were studied both upright (n = 12) and supine (n = 10). With the subject upright at baseline (mean heart rate 77.8 +/- 10.6 beats/min), peak acceleration averaged to 16.8 +/- 3.4 m/s2, and peak modal velocity and flow velocity integral averaged 0.72 +/- 0.14 m/s and 8.4 +/- 2.1 cm, respectively. With pacing at 90 beats/min, peak acceleration decreased to 15.6 +/- 3.6 m/s2, a significant decline from baseline values (p less than 0.005). Similar declines were seen during pacing at 90 beats/min for peak modal velocity and flow velocity integral (0.64 +/- 0.16 m/s and 7.1 +/- 1.9 cm, respectively; both p less than 0.005 versus baseline values). At the peak pacing rate of 140 beats/min, average peak acceleration decreased to 12.8 +/- 3.1 m/s2, and peak modal velocity and flow velocity integral decreased to 0.52 +/- 0.11 m/s and 5.02 +/- 1.25 cm, respectively. A significant linear correlation (r greater than or equal to 0.97, p less than 0.0001) was obtained for the relation between heart rate and peak acceleration, peak modal velocity and flow velocity integral.(ABSTRACT TRUNCATED AT 250 WORDS) .A Harrison MR; Clifton GD; Sublett KL; DeMaria AN. .I 201504 .U 90009750 .S J Am Coll Cardiol 9001; 14(4):936-40 .M Adult; Aged; Blood Flow Velocity; Circadian Rhythm; Coronary Circulation; Echocardiography, Doppler/*; Female; Human; Male; Middle Age; Mitral Valve Insufficiency/*DI/PP; Prospective Studies; Support, U.S. Gov't, P.H.S.. .T Day to day variability of Doppler color flow jets in mitral regurgitation. .P JOURNAL ARTICLE. .W Doppler color flow mapping offers the potential to assess serial changes in mitral regurgitation associated with therapeutic interventions such as surgical valve repair or after-load reduction. However, the day to day variability of color flow jets in mitral regurgitation must be established to distinguish therapeutic responses from random variation. Therefore, 14 patients with mitral regurgitation were each studied on 5 sequential days by color flow velocity mapping. Instrument settings were kept constant for each patient, and no patient had a significant change in heart rate, blood pressure, left ventricular end-diastolic dimension or circumferential wall stress between studies. To assess day to day variability, the area of the Doppler color flow map was carefully measured in multiple views by an experienced echocardiographer. Mitral regurgitant jet area by color flow mapping tended to be greater from apical rather than parasternal views (5.6 +/- 4.0 versus 2.9 +/- 2.1 cm2, respectively, p less than 0.03). The maximal jet area in any view ranged from 0.4 to 15.0 cm2 in individual subjects. Variability of maximal jet area within subjects was not statistically significant by repeated measures analysis of variance (F = 1.88, p = 0.13); however, the coefficient of variation was approximately 15%. Thus, a reduction in jet area of greater than or equal to 30% would be needed to predict a therapeutic response at the 95% confidence level. These data have important implications regarding the use of color flow mapping to assess the efficacy of therapeutic interventions in mitral regurgitation. .A Grayburn PA; Pryor SL; Levine BD; Klein MN; Taylor AL. .I 201505 .U 90009751 .S J Am Coll Cardiol 9001; 14(4):941-6 .M Adult; Aged; Antigens; Cholesterol/BL; Comparative Study; Coronary Disease/*BL/GE; Factor VII/*AN/IM; Factor VIIa/AN; Female; Human; Male; Middle Age; Prospective Studies; Risk Factors; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Triglycerides/BL. .T Elevation of factor VII activity and mass in young adults at risk of ischemic heart disease. .P JOURNAL ARTICLE. .W The Northwick Park Heart Study found that elevation of factor VII in middle-aged subjects was an independent risk factor for subsequent ischemic heart disease. The present study was designed to determine whether factor VII elevation is present at a younger age and whether zymogen or activated factor VII is responsible for this elevation. A group of 20 asymptomatic first degree relatives (mean age 34.9 years) of patients with premature ischemic heart disease were compared with 15 age-matched normal subjects at low risk of ischemic heart disease and 15 older subjects with established ischemic heart disease (mean age 49.7 years). Factor VII procoagulant, coupled amidolytic and antigenic assays, as well as fasting serum triglyceride and cholesterol assays, were performed on all three groups. Factor VII antigen and coagulant activity was significantly elevated in first degree relatives, as was factor VII antigen in the patients with ischemic heart disease. The increased factor VII level in these subjects was caused by elevated factor VII zymogen, not activated factor VII. The results of this study, combined with those of previous studies, suggest that factor VII may be a useful additional marker of the risk for ischemic heart disease and merits further investigation. .A Hoffman CJ; Miller RH; Lawson WE; Hultin MB. .I 201506 .U 90009754 .S J Am Coll Cardiol 9001; 14(4):960-7 .M Angiography; Child, Preschool; Coronary Vessel Anomalies/CO/*DI; Coronary Vessels/RA; Echocardiography/*; False Positive Reactions; Human; Tetralogy of Fallot/*CO. .T Detection of coronary artery abnormalities in tetralogy of Fallot by two-dimensional echocardiography. .P JOURNAL ARTICLE. .W Patients with tetralogy of Fallot have a 5% to 19% incidence rate of abnormal distribution of coronary arteries. These abnormalities are usually detected by angiography and influence the timing and mortality rate of surgery. This study evaluates two-dimensional echocardiography as a method of assessing coronary artery distribution in tetralogy of Fallot. Forty-five consecutive patients with tetralogy of Fallot, aged 0.1 to 20.5 years (mean 5.7 +/- 4.3), had prospective two-dimensional echocardiographic studies to examine the branching patterns of the coronary arteries and to determine the presence or absence of a branch from the right or left coronary artery that crossed the right ventricular outflow tract. The first two patients had known coronary abnormalities and served as learning models. All other echocardiographic studies were performed without knowledge of angiographic or surgical findings. Twenty-two studies were completed before coronary angiography (group A) and 23 after angiography (group B). All eight patients (18%) with coronary abnormalities were correctly identified by two-dimensional echocardiography (five in group A and three in group B). Three had bilateral anterior descending coronary arteries originating from the left and right coronary arteries, two had the anterior descending artery originating from the right coronary artery, two had a large conal branch from the right coronary artery and one had origin of both left and right coronary arteries from a single left ostium. All abnormal coronary arteries were visualized crossing the right ventricular outflow tract, whereas all 21 small conal branches from the right coronary artery were not seen in the right ventricular outflow tract.(ABSTRACT TRUNCATED AT 250 WORDS) .A Jureidini SB; Appleton RS; Nouri S. .I 201507 .U 90009755 .S J Am Coll Cardiol 9001; 14(4):968-76 .M Child, Preschool; Coronary Vessel Anomalies/*DI; Echocardiography/*; Echocardiography, Doppler/*; Fistula/*CN; Heart Catheterization; Heart Defects, Congenital/*DI; Human; Infant; Infant, Newborn; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Diagnosis of coronary artery fistula by two-dimensional echocardiography, pulsed Doppler ultrasound and color flow imaging. .P JOURNAL ARTICLE. .W Ten consecutive patients with a coronary artery fistula, aged 1 day to 4 years, were studied by two-dimensional echocardiography, pulsed Doppler ultrasound and color flow imaging. All patients underwent cardiac catheterization, and seven patients had surgical closure of the fistula. The origin, course and site of drainage of the coronary artery fistula were correctly identified prospectively by echocardiographic examination in all patients. Color flow imaging was particularly helpful in visualizing the site of drainage of the fistula. Diameters of the right and left coronary arteries at their origin and of the aortic root were measured from two-dimensional echocardiographic frames and compared with measurements obtained in normal children. The ratio of coronary artery diameter to aortic root diameter in normal children was 0.14 +/- 0.03 (mean +/- SD) for the right coronary artery and 0.17 +/- 0.03 for the left coronary artery. These normal ratios were greatly exceeded for coronary arteries feeding the fistula, and ranged from 0.68 to 0.84 for the right coronary artery and from 0.34 to 0.52 for the left coronary artery. All anatomic information needed for surgical treatment of coronary artery fistula was consistently obtained by echocardiography with color flow imaging. The fistula was closed from within the heart in five patients and by ligation from the epicardial surface in two patients. In these latter patients, intraoperative color flow imaging at the time of ligation proved to be extremely valuable in achieving complete closure. .A Velvis H; Schmidt KG; Silverman NH; Turley K. .I 201508 .U 90009756 .S J Am Coll Cardiol 9001; 14(4):977-8 .M Coronary Vessel Anomalies/*DI; Echocardiography, Doppler/*; Fistula/*CN; Heart Defects, Congenital/*DI; Human. .T A perspective on color-coded Doppler echocardiography: utility or just another pretty picture? [editorial] .P EDITORIAL. .A Goldberg SJ. .I 201509 .U 90009757 .S J Am Coll Cardiol 9001; 14(4):979-85 .M Adult; Age Factors; Blood Pressure/PH; Echocardiography; Echocardiography, Doppler; Female; Human; Hypertension/DI/*PP; Male; Middle Age; Myocardial Contraction; Stroke Volume/*; Support, Non-U.S. Gov't. .T Determinants of abnormal left ventricular filling in early hypertension. .P JOURNAL ARTICLE. .W Thirty-seven untreated subjects with borderline or mild hypertension were studied to establish the prevalence and clinical characteristics associated with abnormal left ventricular filling in this disorder. Subjects were referred to this study because of casual office blood pressure measurements of greater than or equal to 140/90 mm Hg; all were less than 50 years old, had no other cardiovascular or systemic disease and had not received antihypertensive medication for at least 1 year. To precisely determine blood pressure, measurements were made over 30 min with the patient in the supine position and during awake hours with ambulatory monitoring. Left ventricular mass was determined echocardiographically, and Doppler echocardiography was used to assess left ventricular filling. No subject had increased left ventricular mass, but 8 (22%) of the 37 had abnormal left ventricular filling. All eight subjects with abnormal left ventricular filling had an ambulatory systolic blood pressure greater than 130 mm Hg and a supine systolic blood pressure greater than 122 mm Hg. Abnormal filling was not related to left ventricular mass or heart rate. In multivariate analysis, the degree of abnormal filling could best be predicted from a combination of age and supine systolic blood pressure (r = 0.69; p less than 0.001). This study suggests that in untreated early essential hypertension, abnormal left ventricular filling is present in greater than 20% of subjects, precedes detectable left ventricular hypertrophy and is related to age and prevailing level of blood pressure. .A Phillips RA; Goldman ME; Ardeljan M; Arora R; Eison HB; Yu BY; Krakoff LR. .I 201510 .U 90009758 .S J Am Coll Cardiol 9001; 14(4):986-91 .M Adult; Aged; Angioplasty, Transluminal, Percutaneous Coronary/*; Emergencies; Female; Follow-Up Studies; Human; Male; Middle Age; Mitral Valve Insufficiency/ET/*TH; Myocardial Infarction/CO/*TH; Shock, Cardiogenic/TH; Support, U.S. Gov't, P.H.S.; Time Factors. .T Emergent coronary angioplasty in the treatment of acute ischemic mitral regurgitation: long-term results in five cases. .P JOURNAL ARTICLE. .W Severe mitral regurgitation in the setting of an evolving myocardial infarction is associated with a high operative mortality rate. Five patients with acute severe mitral regurgitation secondary to ischemic posterior papillary muscle dysfunction underwent emergent percutaneous transluminal coronary angioplasty. Two patients were in cardiogenic shock and required intraaortic balloon counterpulsation. Angioplasty resulted in rapid improvement in hemodynamic variables, and all patients were discharged at a mean of 10 days after the procedure. Long-term follow-up study (mean 35 +/- 6 months) revealed normal mitral valve function angiographically and by Doppler echocardiography in four patients. Repeat angioplasty was required in one patient, and another underwent coronary artery bypass surgery without valve replacement for restenosis. One patient developed progressive mitral regurgitation and required elective mitral valve replacement 12 months after angioplasty. These preliminary findings suggest that emergent coronary angioplasty is a useful therapeutic intervention in the treatment of ischemic mitral regurgitation and is associated with a favorable long-term outcome. .A Shawl FA; Forman MB; Punja S; Goldbaum TS. .I 201511 .U 90009760 .S J Am Coll Cardiol 9001; 14(4):999-1002 .M Adult; Aged; Electrocardiography, Ambulatory; Extrasystole/*CI/DI; Female; Human; Hypothyroidism/*DT; Male; Middle Age; Prospective Studies; Thyroxine/AE/*TU. .T Effect of thyroid replacement therapy on the frequency of benign atrial and ventricular arrhythmias. .P JOURNAL ARTICLE. .W Whether thyroid replacement therapy can trigger cardiac arrhythmias in patients with hypothyroidism is not known. In this prospective study, 24 h ambulatory electrocardiographic (ECG) monitoring was used to assess the frequency of atrial and ventricular premature beats in 25 patients with hypothyroidism (5 men and 20 women, aged 56 +/- 3 years) before and 3.5 +/- 0.5 months (mean +/- SEM) after thyroid replacement therapy. Plasma thyroid-stimulating hormone was 73.6 +/- 12.3 and 3.1 +/- 0.6 microU/ml and free thyroxine index was 2.4 +/- 0.4 and 9.8 +/- 0.9 micrograms/100 ml at baseline and after thyroid replacement therapy, respectively. The frequency of ventricular premature beats was not affected by thyroid replacement therapy (from 273 +/- 221 at baseline to 352 +/- 235 beats/24 h after therapy), even in patients with frequent baseline arrhythmias. In contrast, the frequency of atrial premature beats was slightly increased after thyroid replacement therapy (from 47 +/- 17 to 279 +/- 197 beats/24 h), largely as a result of changes seen in three patients. No patient developed new onset of sustained ventricular or supraventricular arrhythmias. Average, basal and maximal heart rates during ECG monitoring increased significantly after thyroid replacement therapy (average 72 +/- 2 to 80 +/- 2; basal 64 +/- 2 to 70 +/- 2; maximal 114 +/- 3 to 130 +/- 3 beats/min, respectively, p less than 0.001). In conclusion, thyroid replacement therapy is safe in patients with common benign cardiac arrhythmias, and does not trigger an increase in arrhythmia frequency except in rare patients with baseline atrial premature beats. It is, however, associated with an increase in basal, average and maximal heart rates. .A Polikar R; Feld GK; Dittrich HC; Smith J; Nicod P. .I 201512 .U 90009763 .S J Allergy Clin Immunol 9001; 84(4 Pt 1):438-9 .M Desensitization, Immunologic/*AE; Human; Hypersensitivity/*TH; Skin Tests. .T Safety of allergen immunotherapy [editorial] .P EDITORIAL. .A Norman PS. .I 201513 .U 90009764 .S J Allergy Clin Immunol 9001; 84(4 Pt 1):440-7 .M Aged; Bay K 8644/PD; Bronchi/*PH; Calcium/*ME; Carbachol/PD; Female; Histamine/PD; Human; Immunization/*; In Vitro; Male; Middle Age; Muscle Contraction/*DE; Muscle, Smooth/*PH; Potassium Chloride/PD; Support, Non-U.S. Gov't. .T Sensitization alters contractile responses and calcium influx in human airway smooth muscle [see comments] .P JOURNAL ARTICLE. .W Although an abnormality in airway smooth muscle has been promoted as a mechanism for airway hyperresponsiveness, there is, so far, little evidence to support this. We investigated whether in vitro hyperresponsiveness to pharmacologic agents could be induced in human airway tissue by passive sensitization and whether these changes in contractile responses were related to an alteration in calcium mobilization. Human bronchial tissue was incubated in serum with a high RAST titer to Dermatophagoides farinae. Control tissues were incubated in serum taken from a skin test-negative donor with a total IgE of less than 10 IU/ml. We compared contractile responses to histamine, KCI, and carbachol in nonsensitized and sensitized tissues and examined the effect on these responses of the calcium voltage-dependent channel agonist, BAY K8644 (10(-6) mol/L). We found that sensitization significantly increased responses to histamine, depressed responses to carbachol, and increased the involvement of the calcium voltage-dependent channel in contractions to KCl. These results suggest that airway hyperresponsiveness may be associated with altered calcium mobilization in airway smooth muscle. .A Black JL; Marthan R; Armour CL; Johnson PR. .I 201514 .U 90009765 .S J Allergy Clin Immunol 9001; 84(4 Pt 1):448-56 .M Allergens/*ST; Antibody Specificity; Grasses/*IM; Human; IgE/*AN; Plant Extracts/ST; Pollen/*IM; Reference Standards; World Health Organization. .T Comparison of in-house allergen extracts of Phleum pratense (timothy grass) pollen with the international standard and investigation of IgE specificities of a grass-pollen serum pool from West Germany and of the one recommended by the World Health Organization. .P JOURNAL ARTICLE. .W We compared our in-house reference extract (RE) and a production extract (PE) with the international reference preparation (IRP) of International Union of Immunological Societies of timothy-grass pollen, using various biochemical and immunochemical methods. Furthermore, we compared the IgE composition of our in-house grass-pollen serum pool (West Germany) with the serum pool recommended by the World Health Organization, using the RE for crossed radioimmunoelectrophoresis (CRIE). Our extracts (RE and PE) were nearly comparable with the IRP. Only by CRIE one more allergen could be detected in RE and PE than in IRP and in another extract purchased from an American company. This finding may depend on the region where the source materials were harvested and which source materials were used for the preparation of the extracts. Furthermore, by high-performance liquid chromatography in the low-molecular-weight range, two distinct peaks could be detected in the nondiafiltered IRP, which were detected in the diafiltered RE and PE as traces only. The IgE composition of our in-house grass-pollen serum pool was comparable with the serum pool recommended by the World Health Organization, as detected by CRIE using RE. .A Wahl R; Meineke D; Oliver J; Schultze-Werninghaus G; Hauck PR. .I 201515 .U 90009766 .S J Allergy Clin Immunol 9001; 84(4 Pt 1):457-64 .M Child; Child, Preschool; Comparative Study; Dose-Response Relationship, Drug; Double-Blind Method; Hay Fever/*DT; Histamine H1 Receptor Blockaders/AD/*PD/TU; Human; Hydroxyzine/*AA/AD/PK/TU; Random Allocation; Support, Non-U.S. Gov't. .T Cetirizine: a pharmacokinetic and pharmacodynamic evaluation in children with seasonal allergic rhinitis. .P JOURNAL ARTICLE. .W In a double-blind, randomized, parallel-group 5-week study, cetirizine, 5 mg or 10 mg daily, was ingested by 10 and nine children, respectively. Cetirizine was rapidly absorbed with mean peak cetirizine concentrations of 427.6 +/- SD, 144.2 ng/ml, 1.4 +/- 1.1 hours after the 5 mg dose, and 978.4 +/- 340.6 ng/ml, 0.8 +/- 0.4 hours after the 10 mg dose. The dose-independent serum-elimination half-life of cetirizine was 7.1 +/- 1.6 hours after cetirizine, 5 mg, and 6.9 +/- 1.6 hours after cetirizine, 10 mg. Urinary excretion of unchanged cetirizine during 24 hours after the initial dose of cetirizine, 5 mg, was 40 +/- 15%, and after cetirizine, 10 mg, it was 39 +/- 14%. The mean histamine-induced wheal-and-flare areas were significantly suppressed from 1 to 24 hours after the first dose of cetirizine, 5 mg, and from 1/2 to 24 hours after the first dose of cetirizine, 10 mg, compared to the mean predose wheal-and-flare areas (p less than 0.01). During daily dosing with cetirizine, 5 mg or 10 mg at bedtime for 35 days, serum cetirizine concentrations and suppression of histamine-induced wheals and flares were monitored every 7 days, 12 hours after the cetirizine dose. The mean serum cetirizine concentrations remained relatively stable during this time, and the mean wheal-and-flare areas remained significantly suppressed (p less than 0.01) compared to baseline wheal-and-flare areas measured before the first dose of cetirizine. The symptoms and signs of allergic rhinitis were suppressed throughout the study by cetirizine, 5 mg and 10 mg.(ABSTRACT TRUNCATED AT 250 WORDS) .A Watson WT; Simons KJ; Chen XY; Simons FE. .I 201516 .U 90009767 .S J Allergy Clin Immunol 9001; 84(4 Pt 1):465-74 .M Adolescence; Adult; Aged; Child; Female; Human; Hypersensitivity/*EP; Male; Middle Age; Pollen/*IM; Prevalence; Skin Tests/*. .T Quantitative studies of cutaneous hypersensitivity: the prevalence of epicutaneous flare reactions to allergenic pollen extracts. .P JOURNAL ARTICLE. .W The flare reactions produced by epicutaneous tests with 68 undiluted allergenic pollen extracts were measured in 550 allergic patients. Skin test reactions greater than or equal to 2, greater than or equal to 5, greater than or equal to 10, greater than or equal to 20, and greater than or equal to 30 mm in diameter, respectively, were detected in approximately 67%, 22%, 10%, 3%, and 1% of the 34,700 skin tests. With the Kolmogorov-Smirnov difference test, the cumulative frequency of reaction diameters and loge-transformed diameters of all reactions and reactions to individual allergenic extracts differed significantly (p less than or equal to 0.01) from a normal distribution. The ability to identify specific differences between reactions to closely related pollen extracts was evaluated. Specific reactions could be reliably identified with greater than or equal to 10 mm diameter flares. This arbitrary conservative threshold was used to estimate the relative prevalence of positive reactions to each allergenic extract. Seven allergenic extracts elicited the first quartile of all positive reactions. Thirteen, 18, and 30 allergenic extracts, respectively, were needed to elicit the second, third, and fourth quartiles of all positive reactions. Reactions to amphiphilous, as well as anemophilous, pollens were detected. Skin test reactions to grasses were more prevalent than reactions to weeds and trees. The most informative allergenic extracts for the detection of patients who exhibited a positive reaction to any extract were from red fescue-grass pollens, mesquite, short ragweed, red clover, and timothy-grass pollens. .A Lucas SK; Buckley CE 3d. .I 201517 .U 90009768 .S J Allergy Clin Immunol 9001; 84(4 Pt 1):475-83 .M Adolescence; Adult; Female; Follow-Up Studies; Food Hypersensitivity/*DH; Food Preferences; Human; Male; Middle Age. .T Role of the elimination diet in adults with food allergy. .P JOURNAL ARTICLE. .W The aim of the study was to check whether, after a period of complete exclusion of the offending foods in adult subjects suffering from food allergy, these foods could subsequently be safely reintroduced into the diet. Patients with chronic urticaria and/or perennial rhinitis negative for secondary pathology or other allergies were subjected to a strict diagnostic protocol for food allergy. Briefly, out of a case list of 207 patients, we found 23 patients whose symptoms were clearly related, on open reintroduction, to at least one food. The really offending foods in these patients were subsequently identified by double-blind, placebo-controlled food challenges. Only 10 of the 23 patients had positive challenges for 13 foods. Double-blind challenges were repeated after 1 year or more of avoidance of the offending foods to evaluate the persistence or disappearance of sensitivity. We found that five (38%) of the 13 previously offending foods were well tolerated. Thus, in adults, as previously proved in children, dietary avoidance of the offending foods appears to be an effective measure for dealing with food allergy. The kind of foods involved and the completeness of their avoidance appeared to be important factors favoring the reestablishment of tolerance in adults. .A Pastorello EA; Stocchi L; Pravettoni V; Bigi A; Schilke ML; Incorvaia C; Zanussi C. .I 201518 .U 90009769 .S J Allergy Clin Immunol 9001; 84(4 Pt 1):484-91 .M Adolescence; Adult; Asthma/DT/*MO; Child; Cluster Analysis; Emergencies; Environment; Human; Patient Compliance/*; Support, Non-U.S. Gov't; Theophylline/TU. .T Investigation of a cluster of deaths of adolescents from asthma: evidence implicating inadequate treatment and poor patient adherence with medications. .P JOURNAL ARTICLE. .W We investigated a cluster of five deaths of adolescents from asthma in St. Louis during a 3-month period in 1987. Although the cluster represented a statistically significant increase in the number of asthma deaths in this age group over that observed in previous years, no common exposure to environmental, infectious, or therapeutic agents could be identified. The patterns of hospital admissions for asthma and emergency room visits at the two pediatric hospitals in the community did not suggest an increase in the frequency or severity of asthma during this time. Despite the lack of evidence for common exposure, the decedents shared many personal and medical characteristics. All decedents were black patients and were of lower socioeconomic status. All were adolescents and were responsible for regulating their own medication schedules. Lack of appreciation of the severity of their asthma by medical personnel and the patients' families was evident. For example, two patients with severe asthma had not been prescribed inhaled corticosteroids. In addition, the four decedents tested had markedly subtherapeutic or zero serum theophylline levels measured at the time of the fatal episode, even though appropriate amounts of theophylline had been prescribed. Their theophylline levels were substantially lower than levels in patients of the same age observed at the emergency room or hospitalized for asthma during the same time period. Continued efforts to educate adolescent patients, their families, and medical care providers about the treatment of asthma are warranted. .A Birkhead G; Attaway NJ; Strunk RC; Townsend MC; Teutsch S. .I 201519 .U 90009770 .S J Allergy Clin Immunol 9001; 84(4 Pt 1):492-501 .M Eosinophils/ME; Histamine Liberation; Human; Hypersensitivity/*ET; Nose/*IM; Pollen/IM; Prostaglandin D2/AN; Sneezing; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Observations on the pathogenesis of nasal priming. .P JOURNAL ARTICLE. .W To understand better the response of patients with allergic rhinitis to nasal challenge with antigen, we studied the mechanism of priming, that is, the increased clinical response to daily sequential nasal challenges. Ten subjects with ragweed hay fever were challenged four times with increasing doses of ragweed pollen. The first 2 challenge days were separated by 2 weeks, whereas the last three challenges occurred on sequential days. Nasal lavages, performed before and after each nasal challenge, were evaluated for levels of inflammatory mediators and cellular content. In contrast to control days, a significant (p less than 0.05) increase in the number of sneezes occurred on both priming days. Priming was associated with a significant increase in the level of histamine on both priming days, whereas the second priming day was also associated with an increase in TAME-esterase activity, kinins, and prostaglandin D2 obtained after challenge (p less than 0.05 for all). In the lavages before challenge on the priming days, the total number of cells and the number of neutrophils, eosinophils, and alcian blue-positive cells were significantly increased, but in contrast, basal levels of mediators were not. The net increase in the number of alcian blue-positive cells correlated with the net increase in the amount of histamine released on the priming days (r = 0.661; p less than 0.05). These studies suggest that priming results, in part, from increased mediator release from influxing inflammatory cells. .A Wachs M; Proud D; Lichtenstein LM; Kagey-Sobotka A; Norman PS; Naclerio RM. .I 201520 .U 90009771 .S J Allergy Clin Immunol 9001; 84(4 Pt 1):501-6 .M Adult; Aged; Aged, 80 and over; Basophils/*; Comparative Study; Eosinophils; Female; Follow-Up Studies; Histamine/*BL; Histamine Liberation/*; Human; IgE/AN; Leukocyte Count; Male; Middle Age; Neoplasms/*BL; Support, Non-U.S. Gov't. .T Comparison between number of basophils, blood histamine, and histamine release in cancer and noncancer patients. .P JOURNAL ARTICLE. .W In cancer patients with primary tumor with or without metastasis or metastasis alone, by comparison with healthy subjects and noncancer patients, the decrease in blood histamine levels is due to a decrease in total basophil number. These basophils have a normal content of histamine (1 to 2 pg per basophil) and are able to release histamine. The percentage of anti IgE-induced histamine release is not significantly different than in noncancer patients. The scarcity of basophils in cancer patients is not due to a leukopenia. Blood histamine levels and total basophil number are normal in patients after successful excision of their primary tumor without metastasis. .A Galoppin L; Noirot C; Wastiaux JP; Scheinmann P; Paupe J; Burtin C. .I 201521 .U 90009772 .S J Allergy Clin Immunol 9001; 84(4 Pt 1):507-14 .M Antibodies/*AN; Asthma/CI/*DI; Cyanates/*IM; Female; Human; IgE/AN; IgG/AN; Male; Occupational Diseases/CI/*DI; Skin Tests; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Specific serum antibodies against isocyanates: association with occupational asthma. .P JOURNAL ARTICLE. .W Although increased levels of specific IgE and/or IgG antibodies have been documented in individual cases of occupational asthma caused by common types of isocyanates (hexamethylene diisocyanate [HDI] and diphenylmethane diisocyanate [MDI]), the frequency among workers with occupational asthma is still unknown. The sera of 62/65 workers referred for specific inhalation challenges with isocyanates were analyzed for the presence of specific antibodies to the relevant isocyanate. Most workers (39, 63%) were exposed to HDI, some to MDI (17, 27%), and a few to toluene diisocyanate (six, 10%). Specific inhalation challenges were positive in 29 subjects, eliciting either immediate (seven), early late (two), late (13), or dual (seven) reactions. Specific inhalation challenges were more often positive in those subjects with increased nonspecific bronchial responsiveness. Twenty-nine subjects demonstrated increased levels of specific IgE and/or IgG antibodies to isocyanates in the absence of antibodies against human serum albumin (increased IgE only, no subject; IgG only, 20; both IgE and IgG, nine subjects). Although there was a loose association between the results of specific inhalation challenges and levels of specific IgE, the association was much better with the level of specific IgG. Indeed, 21 of the 29 subjects (72%) with positive challenges had increased levels of specific IgG, whereas 25 of the 33 subjects (76%) with negative challenges had normal levels of antibodies. The association was significant with both HDI and MDI. The levels of antibodies were not significantly associated with the type of temporal reaction.(ABSTRACT TRUNCATED AT 250 WORDS) .A Cartier A; Grammer L; Malo JL; Lagier F; Ghezzo H; Harris K; Patterson R. .I 201522 .U 90009774 .S J Allergy Clin Immunol 9001; 84(4 Pt 1):520-8 .M Allergens/*IM; Animal; Animals, Laboratory/*IM; Environmental Exposure; Enzyme-Linked Immunosorbent Assay; Human; Hypersensitivity/*IM; IgG/*AN; Mice; Mice, Inbred Strains; Rabbits; Rats; Support, Non-U.S. Gov't. .T IgG antibodies in relation to exposure to laboratory-animal allergens. .P JOURNAL ARTICLE. .W An ELISA technique has been used to measure levels of specific IgG in individuals exposed to laboratory animals in comparison to levels in unexposed individuals. The technique was to determine whether these levels could be useful as a monitor of exposure. Both symptomatic (with and without specific IgE) and nonsymptomatic individuals were studied. Several antigenic source materials were investigated for each animal. The IgG response was extremely complex and elicited a varied pattern of response between animals (mouse, rat, and rabbit). No evidence was found for raised IgG levels being directly related to the degree of exposure, more to the presence of clinical symptoms and specific IgE. Long-term heavy exposure to rats in nonsymptomatic individuals appeared to produce a suppression of the IgG response in relation to control levels. These findings suggest that IgG is not an indicator of exposure but demonstrate a varied response related to the presence of specific allergy to an animal, the particle size on which antigens are carried, and the physiologic state of the mucosa onto which the particles impact. .A Price JA; Longbottom JL. .I 201523 .U 90009775 .S J Allergy Clin Immunol 9001; 84(4 Pt 1):529-37 .M Allergens/*ST; Comparative Study; Densitometry; Electrophoresis, Polyacrylamide Gel; Human; Immunoblotting; Isoelectric Focusing; Plant Extracts/*ST. .T Use of enzyme-developed immunoblots scanned by densitometry to compare lot-to-lot variability of Russian-thistle extracts. .P JOURNAL ARTICLE. .W Two different lots of Russian-thistle extracts from five commercial sources were evaluated by isoelectric focusing, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunoblots of Immobilon transfers from these separations. The immunoblots were developed by an enzyme-linked method and scanned with a densitometer. The two lots of a standardized extracts produced scans that suggested uniformity in allergenic components. Several of the nonstandarized extract lots also appeared quite comparable. With further refinement, immunoblotting with densitometric analysis appears to offer an attractive way to standardize allergen extracts. .A Mansfield LE; Tan M; Martinez G; Rael E; Harris NS. .I 201524 .U 90009778 .S J Allergy Clin Immunol 9001; 84(4 Pt 1):556-61 .M Chromatography, High Pressure Liquid; IgG/*AN/CL; Infusions, Intravenous; Molecular Weight. .T Immunoglobulin composition of three commercially available intravenous immunoglobulin preparations. .P JOURNAL ARTICLE. .W To evaluate whether significant differences in immunoglobulin composition exist among the three commercially available intravenous immunoglobulin (IVIG) preparations, we compared three of these products in terms of their quantitative immunoglobulin concentration, IgG subclass concentration, and the presence of IgG aggregates. Three different lots were tested for each of the IVIG formulations, and the IgG subclass assays were performed by three different laboratories. Differences were found among the three formulations in subclass concentration and aggregate content. Sandoglobulin (Sandoz Pharmaceuticals, East Hanover, N.J.) contained a significantly higher amount of IgG2 (p less than 0.002) compared to the other formulations. All the formulations tested were found to be deficient in IgG4 relative to the World Health Organization standards, with Gammagard (Hyland Therapeutics, Glendale, Calif.) demonstrating only negligible amounts. Immunoglobulin aggregate content was different among manufacturers with Gamimmune N (Cutter Biological, Berkeley, Calif.) containing the highest amount of monomer IgG (99.8%). Significant differences were found in the subclass results obtained by the ICN ImmunoBiologicals assay (Lisle, Ill.), compared to the two reference laboratories. This difference among the subclass assays raises the question as to the use of these assays in the evaluation of patients with suspected subclass deficiencies. The differences in subclass concentration and aggregate content in IVIG preparations were great, and future clinical trials with these formulations would be indicated to determine the clinical significance of these findings. .A Herrera AM; Saunders NB; Baker JR Jr. .I 201525 .U 90009779 .S J Allergy Clin Immunol 9001; 84(4 Pt 1):562-4 .M Enzyme-Linked Immunosorbent Assay/*; Human; IgG/*AN; Middle Age. .T Reverse-sandwich ELISA may underestimate antibody titers [letter; comment] .P COMMENT; LETTER. .A van Ree R; Stapel SO; Aalberse RC. .I 201526 .U 90009780 .S J Allergy Clin Immunol 9001; 84(4 Pt 1):564 .M Acquired Immunodeficiency Syndrome/*TM; AIDS Serodiagnosis/*ST; Blood Transfusion/*AE; Human; Risk Factors. .T AIDS test accuracy and transfusion-associated AIDS: comments on Saxon and Campen [letter; comment] .P COMMENT; LETTER. .A Cantani A. .I 201527 .U 90009781 .S J Allergy Clin Immunol 9001; 84(4 Pt 2):565-648 .M Human; Immunization, Passive/*; Immunoglobulins/*AD; Immunologic Deficiency Syndromes/*TH; Infusions, Intravenous; Support, Non-U.S. Gov't. .T Mechanisms and uses of intravenous immune globulin in primary ond secondary immune deficiency disorders. Naples, Florida, October 13-14, 1988. .P JOURNAL ARTICLE. .I 201528 .U 90009785 .S J Allergy Clin Immunol 9001; 84(4 Pt 2):595-601; discussion 601-2 .M Agammaglobulinemia/IM/TH; B-Lymphocytes/IM; Human; Immunization, Passive/*; Immunoglobulins/*BI; In Vitro; Infusions, Intravenous; Suppressor Cells/*IM; T4 Lymphocytes/IM. .T Modulation of in vitro synthesis of immunoglobulin and the induction of suppressor activity by therapy with intravenous immune globulin. .P JOURNAL ARTICLE. .W Intravenous immune globulin has become an important modality of replacement therapy for children and adults with hypogammaglobulinemia or agammaglobulinemia. It is also evident that intravenous immune globulin is effective in patients with a variety of automimmune disorders. The present study was undertaken to evaluate the effects of intravenous immune globulin replacement therapy in patients with common variable hypogammaglobulinemia. We measured pokeweed mitogen-induced immunoglobulin synthesis of patients' peripheral blood mononuclear cells cocultured in equal numbers with normal subjects' lymphocytes to assess suppressor cell activity. The mean suppressor cell activity in coculture experiments at baseline of nine patients in the study was -16%. Suppressor activity was demonstrated in two of nine patients at baseline who received intravenous immune globulin therapy before initiation of the study. After intravenous immune globulin therapy at a low dose (100 to 200 mg/kg/mo), suppressor cell activity was demonstrated in all nine patients, which ranged from -63% to -100%. In five patients intravenous immune globulin therapy was discontinued for 4 months. There was a return to baseline levels, with suppressor activity ranging from -20% to -50%. On reinstitution of high-dose intravenous immune globulin therapy (300 to 400 mg/kg/mo), all patients except one again demonstrated increased suppressor cell activity. Cell separation and recombination cell culture experiments were performed. All patients had an intrinsic B cell defect before the initiation of therapy so that the effects of intravenous immune globulin therapy on B cell function could not be assessed. Combining normal B cells with the patient's T cell-enriched fraction showed marked suppression of pokeweed mitogen-induced immune globulin synthesis. This suppression was reversible by irradiation of the T cell fraction. Removal of CD8-positive T cells by cell sorting resulted in normal immunoglobulin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) .A Ballow M; White W; Desbonnet C. .I 201529 .U 90009786 .S J Allergy Clin Immunol 9001; 84(4 Pt 2):603-6; discussion 607 .M Adolescence; Child; Female; Human; Immunization, Passive/*; Infusions, Intravenous; Male; Seizures/IM/*TH. .T Use of intravenous immune globulin in the treatment of seizure disorders. .P JOURNAL ARTICLE. .W Recurrent seizures are a significant cause of childhood morbidity. Often the underlying pathogenesis is unknown. Studies from several laboratories have suggested a relationship between perturbations of humoral immunity and clinical epilepsy. Brain-specific antigens have been observed in the systemic circulation after brain injury. This can be followed by the appearance of antibodies to neuronal tissues in both serum and cerebrospinal fluid. Moreover, there appears to be disproportionate representation of persons with coexisting humoral immune deficiencies among patients with chronic epilepsy. Interestingly, a potent immunosuppressant, adrenocorticotropic hormone, has long been the principal treatment for infantile spasms. Given this body of information associating humoral immunity with recurrent seizures, several investigators have recently attempted to treat intractable childhood epilepsy with high-dose intravenous immune globulin. Although the number of patients treated is small and it is not possible to make comparisons between individual studies, nevertheless the results have been encouraging. Five patients with intractable seizures who failed to respond to conventional therapy were treated with an outpatient regimen of intravenous immune globulin (1 gm/kg/day) for 2 days. Two patients showed significant clinical improvement while a third had an equivocal response. Immunologic analysis of these patients before therapy revealed a surprisingly high incidence of immune abnormalities. We conclude that intravenous immune globulin may be useful in the treatment of selected patients with chronic epilepsy unresponsive to anticonvulsants. .A Schwartz SA; Gordon KE; Johnston MV; Goldstein GW. .I 201530 .U 90009788 .S J Allergy Clin Immunol 9001; 84(4 Pt 2):613-5; discussion 615-6 .M Arthritis, Juvenile Rheumatoid/*TH; Dermatomyositis/*TH; Human; Immunization, Passive/*; Infant; Infusions, Intravenous; Vasculitis/*TH. .T The use of intravenous immune globulin in collagen vascular disorders: a potentially new modality of therapy. .P JOURNAL ARTICLE. .W During the last several years, there has been increasing interest in the use of intravenous immune globulin for immunosuppression. Although the mechanism(s) of action remains to be delineated, immune globulin therapy has been shown to be effective in some antibody-mediated disorders. In Rh disease, antibody-induced cytopenias, myasthenia gravis, and the clotting disorder associated with anti-factor VIII antibody, intravenous immune globulin has had therapeutic benefit. It was of interest that intravenous immune globulin may partially ameliorate the tendency toward dilation of the coronary vessels in Kawasaki disease. If this disorder represents a vasculitis of the small feeding vessels of the coronary arteries, could this agent influence other forms of collagen vascular disease? Pilot studies in dermatomyositis and polymyositis and systemic juvenile rheumatoid arthritis indicate benefit from intravenous immune globulin therapy. In these studies we used a high-dose protocol consisting of 1 gm/kg/day of immune globulin for 2 days every 4 weeks. In patients with either myositis or systemic juvenile rheumatoid arthritis, beneficial effects were seen. In the former group of patients, increased proximal muscle strength and reduction in creatine kinase levels were observed. In the latter group of patients a marked reduction in systemic features was observed. The amount of corticosteroids required was reduced in both groups of patients. These studies indicate the potential for intravenous immune globulin in collagen vascular disorders and the need for carefully controlled trials of this form of therapy. .A Gelfand EW. .I 201531 .U 90009793 .S J Am Diet Assoc 9001; 89(10):1432, 1434, 1436 .M Dietetics/*; Food Labeling/*LJ; Societies/*; United States. .T ADA testifies in support of food labeling legislation. .P JOURNAL ARTICLE. .I 201532 .U 90009794 .S J Am Diet Assoc 9001; 89(10):1441-3 .M Dietetics/*TD; United States. .T Probing the envelope of dietetics by transforming challenges into opportunities [see comments] .P JOURNAL ARTICLE. .A Finn SC; Rinke W. .I 201533 .U 90009798 .S J Am Diet Assoc 9001; 89(10):1458-64 .M Analysis of Variance; Certification; Chi-Square Distribution; Dietetics/*; Education, Graduate; Hospitals, General; Human; Questionnaires; Specialism/*; United States. .T Dietetic specialization: opinions of directors of departments of dietetics. .P JOURNAL ARTICLE. .W The need for specialists in dietetic practice was studied by surveying a stratified, random sample of 750 directors of departments of dietetics from nonfederal, general medical-surgical hospitals with more than 75 beds. The response rate was 72%. The majority of respondents were directors who considered themselves generalists. Five demographic variables used in data analysis were hospital size, education level, registration status, years of experience, and perception of practice as generalist or specialist. Student's t-test and analysis of variance were the principal methods of statistical analysis. Results indicated that respondents supported dietetic specialization; however, they emphasized the value of undergraduate generalist preparation as enhancing job performance and preventing fragmentation of the profession. Respondents indicated that specialization should follow professional work experience and additional education. Respondents stressed that The American Dietetic Association should be responsible for determining the process of dietetic specialization. Education level was the variable most likely to affect response. Respondents with education beyond the baccalaureate level were more likely than those with only a bachelor's degree to agree that specialization should occur after professional experience and at the graduate level. .A Sandrick JG. .I 201534 .U 90009800 .S J Am Diet Assoc 9001; 89(10):1473-7 .M Analysis of Variance; Comparative Study; Female; Food/*; Human; Male; Nutrition/*ED; Sex Factors; Size Perception/*. .T The impact of training, food type, gender, and container size on the estimation of food portion sizes. .P JOURNAL ARTICLE. .W Students in a large introductory nutrition course were divided into two groups, one that received training on estimating food quantities and one that received no instruction. Training consisted of 10-minute sessions in which 76 subjects (in groups of 10) passed around and viewed food models labeled with their portion sizes while one of the investigators verbally indicated the quantities. Immediately following instruction, the trained subjects individually estimated portion sizes of one of four displays of six foods: two solids (meat loaf and fish), two liquids (milk and soup), and two amorphous items (spaghetti and apple sauce). The second group of subjects, who had received no training, also estimated the same portion sizes of the same foods in the same displays. The four displays were set up in separate rooms, with the same foods and portion sizes in each, but different container size combinations were used (smaller vs. larger containers). Both training and type of food had a significant effect; training improved estimations, and, in general, solids were better estimated than liquids, which were better estimated than amorphous items. Although results were mixed, women tended to estimate more accurately than men. There was some tendency for estimates to be more accurate when made for foods in small containers. The authors conclude that a training session enhances the accuracy of individuals estimating food quantity and that accuracy of estimates differs for different food types. .A Yuhas JA; Bolland JE; Bolland TW. .I 201535 .U 90009801 .S J Am Diet Assoc 9001; 89(10):1478-80, 1483 .M Counseling; Dietary Services/*; Dietetics/*; Human; Interviews; Marketing of Health Services/*. .T Care plans for marketing and sales opportunities. .P JOURNAL ARTICLE. .W Similarities exist between marketing/sales behaviors and the skills dietitians practice in the development and implementation of nutrition care plans. A parallel process can be followed throughout the nutrition care plan and the sales call. Market research is completed prior to the sales call with the client. The product or service and the desired outcome are identified. Sales strategies make up the interactive skills used to accomplish the marketing plan. .A Moore CH. .I 201536 .U 90009802 .S J Am Diet Assoc 9001; 89(10):1484-8 .M Calcium, Dietary/*AD/TU; Eating/*; Female; Human; Longitudinal Studies; Middle Age; Osteoporosis/PC; Questionnaires/*; Seasons; Support, Non-U.S. Gov't. .T Validation of a quantitative food frequency questionnaire for rapid assessment of dietary calcium intake. .P JOURNAL ARTICLE. .W This study tested the accuracy of a quantitative food frequency questionnaire (FFQ) designed to assess the amount of calcium consumed daily and to use as an educational tool in diet counseling and for prescribing calcium supplementation. The subjects were 26 perimenopausal women, aged 48 to 56 years, who were participants in a longitudinal osteoporosis study. Diets of the subjects were studied during the winter and summer of one year. Subjects filled out a food frequency questionnaire and the next week completed 4-day food intake records according to instructions from the researchers. The mean daily intake of calcium estimated from the food frequency questionnaire was 928 mg in the winter and 912 mg 6 months later. Ranges in the winter were 227 to 2,243 mg calcium and in the summer 198 to 3,063 mg calcium. The 53-item FFQ included descriptions of portion sizes and a calcium index for each item and had options for two frequency periods. The calcium level estimated from the questionnaire correlated (r = .73 in winter and r = .84 in summer) with the estimated amount from 4-day records. A seasonal difference was not found. The brief time (less than 5 minutes by a dietitian) required to calculate the amount of calcium consumed daily from the food frequency questionnaire could make it an important clinical tool. .A Musgrave KO; Giambalvo L; Leclerc HL; Cook RA; Rosen CJ. .I 201537 .U 90009805 .S J Am Diet Assoc 9001; 89(10):1499-500 .M Body Weight; Dietary Services/*ST; Human; Medical Records; Nursing Homes/*ST; Quality Assurance, Health Care/*LJ; United States. .T Quality assessment and assurance in a long-term care facility: meeting current federal requirements. .P JOURNAL ARTICLE. .A Herbelin K. .I 201538 .U 90009807 .S J Am Diet Assoc 9001; 89(10):1502-4 .M Aged; Aged, 80 and over; Database Management Systems; Dietary Services/*; Food Services; Human; Information Systems/*; Massachusetts; Questionnaires; Software. .T Computer use in Massachusetts elderly nutrition programs. .P JOURNAL ARTICLE. .A Messina MS; Balsam AL. .I 201539 .U 90009808 .S J Am Diet Assoc 9001; 89(10):1504-6 .M Adolescence; Ambulatory Care/*; Cerebral Palsy/*/CO; Child; Child, Preschool; Dietary Services/*; Growth Disorders/CO/*DH; Hawaii; Human; Infant; Infant, Newborn; Nutritional Status. .T Establishing outpatient nutrition services for children with cerebral palsy. .P JOURNAL ARTICLE. .A Johnson RK; Maeda M. .I 201540 .U 90009810 .S J Am Geriatr Soc 9001; 37(10):1003-4 .M Aged; Cardiovascular Diseases/*PP; Coitus/*; Hemiplegia/*PP; Human; Male; Middle Age. .T Sexual function among male hemiparetic post-CVA patients [letter] .P LETTER. .A Habot B; Rabinovitz H; Friedman JB; Schwartz J; Tulchinsky TH. .I 201541 .U 90009811 .S J Am Geriatr Soc 9001; 37(10):1004 .M Human; Muscle Cramp/*TH; Urination/*. .T Night muscle cramps [letter] .P LETTER. .A Kiveloff B. .I 201542 .U 90009812 .S J Am Geriatr Soc 9001; 37(10):1004 .M Cimetidine/*AD; Drug Utilization/*EC; Human; Nursing Homes/*; Ranitidine/*AD. .T Overuse of H2-blockers in a nursing home [letter] .P LETTER. .A Oldendorf M. .I 201543 .U 90009813 .S J Am Geriatr Soc 9001; 37(10):1004 .M Dementia/*DI; Human; Posture/*. .T Straight or oblique? [letter] .P LETTER. .A Pines A; Levo Y. .I 201544 .U 90009815 .S J Am Geriatr Soc 9001; 37(10):937-43 .M Activities of Daily Living; Adult; Aged; Aged, 80 and over; Comparative Study; Emergency Service, Hospital/*UT; Female; Health Surveys; Human; Male; Middle Age; Outcome and Process Assessment (Health Care)/*; Patient Compliance; Patient Discharge/*; Prospective Studies. .T Short-term outcomes of elderly patients discharged from an emergency department. .P JOURNAL ARTICLE. .W To determine the short-term functional and medical outcomes and predictors of outcome following discharge from an acute hospital emergency department, 100 elderly (greater than or equal to 65 yr) and 100 nonelderly (less than 65 yr) patients were studied prospectively. Patients were interviewed at three days and again at three weeks following emergency department discharge. The number of new prescriptions given to both groups in the emergency department was similar (elderly 41%; nonelderly, 31%). The elderly were as likely as the nonelderly to know the correct name (elderly, 88%; nonelderly, 87%), dosage schedule (elderly, 90%; nonelderly, 90%) and purpose (elderly, 85%; nonelderly, 94%) of their new medications. There was no difference in patients' understanding of the diagnosis (elderly, 72%; nonelderly, 72%) or in medication compliance (elderly, 81%; nonelderly, 74%). Elderly patients were more likely to keep scheduled follow-up appointments (87% vs 65%; P less than .05). Despite these similarities the elderly had worse medical outcomes at three weeks; 67% of the elderly were better and 20% were worse, including seven patients who required interim hospitalization, four of whom died. In contrast, 82% of the nonelderly were better and only 4% were worse (P less than .01). None of the nonelderly required hospitalization or had died. Functional impairments were more common in the elderly both at baseline (elderly, 26%; nonelderly, 6%; P less than .01) and at three weeks (elderly, 27%; nonelderly, 5%; P less than .001). Independent predictors of poor medical outcome included age greater than or equal to 65 (P less than .009) and functional impairment at baseline (P less than .022).(ABSTRACT TRUNCATED AT 250 WORDS) .A Denman SJ; Ettinger WH; Zarkin BA; Coon PJ; Casani JA. .I 201545 .U 90009816 .S J Am Geriatr Soc 9001; 37(10):944-8 .M Adolescence; Adult; Aged; Aged, 80 and over; Aging/*IM; Child; Child, Preschool; Comparative Study; Graves' Disease/*CO/IM; Human; Hyperthyroidism/*ET/IM; Infant; Middle Age; Thyroglobulin/BL/IM; Thyroid Function Tests; Thyroxine/BL/IM; Triiodothyronine/BL/IM. .T Age-related changes of thyroid function and immunologic abnormalities in patients with hyperthyroidism due to Graves' disease. .P JOURNAL ARTICLE. .W In order to clarify the reasons why hyperthyroidism due to Graves' disease is mild in aged patients compared to young patients, we examined the degree of hyperthyroidism and immune abnormalities in 371 untreated patients. The patients were divided into nine groups based on their age; groups A to I consisted of patients aged 0-9, 10-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80-89 years, respectively. Serum thyroxine (T4), triiodo-thyronine (T3), and thyroglobulin levels were highest in group B (patients aged 10-19 years) and decreased progressively with advancing age. T3/T4 ratio was also highest in group B and decreased progressively with age. These data reconfirmed that the degree of hyperthyroidism is milder in older patients. The prevalence of positive microsomal and thyroglobulin antibodies was highest in group B (patients aged 10-19 years) and progressively lower in older groups, suggesting that an association with Hashimoto's thyroiditis is less prevalent in aged patients. We suggest that hyperthyroidism due to Graves' disease is mild in aged patients because responsiveness of the thyrocyte to the abnormal stimulator, thyrotropin-receptor antibody, may be reduced. Such reduced responsiveness may not be due to Hashimoto's thyroiditis, since the prevalence of antithyroid antibodies is lower in aged than in younger patients with hyperthyroidism due to Graves' disease. .A Aizawa T; Ishihara M; Hashizume K; Takasu N; Yamada T. .I 201546 .U 90009818 .S J Am Geriatr Soc 9001; 37(10):957-62 .M Age Factors; Aged; Attitude to Health; Cross-Sectional Studies; Data Collection; Educational Status; Female; Human; Income; Mammography/*UT; Middle Age; Patient Compliance/*; Support, Non-U.S. Gov't. .T Effects of age, education, and physician advice on utilization of screening mammography. .P JOURNAL ARTICLE. .W We investigated the utilization of mammography as a screening test for breast cancer in a middle-income Connecticut suburban community of 30,000 people. The sampling frame was community-dwelling women aged 30 years and over who had telephones. Random digit telephone survey methods were used to identify a sample of 470 eligible subjects. Of those eligible to be included, 350 or 74.4% completed the interview. Analysis of data from the 171 respondents aged 50 years or greater indicated that women aged 65-80 years had a significantly lower rate of screening mammography than did women aged 50-64 years (means 2 = 6.6, P = .01). When further analysis was done to take into account the effects of education and of income on these rates, the association of age with mammography utilization was no longer statistically significant. Among women who recalled their physician advising a mammogram, 88% had had one performed. Among women who could not recall their physician advising a mammogram, 7% had had one. The impact of physician advice was statistically significant (means 2 = 110.3, P less than .001). Physicians recommended screening mammography less for patients with low level of education (means 2 = 21.6, P less than .001), low income (X2 = 7.8, df = 2, P = .02) and greater age (means 2 = 14.2, P = .003). We conclude that utilization of screening mammography in the community studied is related more strongly to education and to income than to age. The bivariate association of mammography utilization with age may be attributable to a cohort effect, rather than an age effect.(ABSTRACT TRUNCATED AT 250 WORDS) .A Coll PP; O'Connor PJ; Crabtree BF; Besdine RW. .I 201547 .U 90009820 .S J Am Geriatr Soc 9001; 37(10):970-3 .M Age Factors; Aged; Alzheimer's Disease/*ET; Dementia/*ET; Head Injuries/*CO; Human; Injury Severity Score; Middle Age; Retrospective Studies; Time Factors. .T Severe head injury hastens age of onset of Alzheimer's disease. .P JOURNAL ARTICLE. .W Head trauma has been found with greater frequency in the histories of Alzheimer patients than age-matched controls in some studies, but not in others. We hypothesized that events that accelerate neuron loss, such as significant head trauma, hasten the onset of symptoms of Alzheimer's disease in persons vulnerable to the disorder. Retrospective data on 148 probable Alzheimer patients and 33 demented controls were examined. Alzheimer patients with severe head injury before the age of 65 showed onset of symptoms at an earlier age than Alzheimer patients without head trauma. .A Gedye A; Beattie BL; Tuokko H; Horton A; Korsarek E. .I 201548 .U 90009821 .S J Am Geriatr Soc 9001; 37(10):974-6 .M Aged; Aged, 80 and over; Alzheimer's Disease/*PX; Awareness/*; Case Report; Cognition/*; Emotions; Female; Human; Male; Nursing Homes; Reality Therapy/*. .T Adverse effects of reality orientation. .P JOURNAL ARTICLE. .A Dietch JT; Hewett LJ; Jones S. .I 201549 .U 90009822 .S J Am Geriatr Soc 9001; 37(10):977-9 .M Aged; Aged, 80 and over; Arthroscopy; Case Report; Human; Knee Injuries/DI/*SU; Male; Osteoarthritis/DI/*SU; Postoperative Period. .T Arthroscopy in the geriatric patient. Acute injuries and chronic joint diseases. .P JOURNAL ARTICLE. .A Ruffin MT 4th; Hunter RE. .I 201550 .U 90009823 .S J Am Geriatr Soc 9001; 37(10):980-2 .M Aged; Aged, 80 and over; Emergencies; Female; Femoral Neck Fractures/*CO/TH; Human; Injections, Epidural; Male; Methadone/*AD; Middle Age; Pain/*DT/ET; Pain Measurement. .T Epidural methadone for analgesic management of patients with conservatively treated proximal femoral fractures. .P JOURNAL ARTICLE. .W Epidural methadone analgesia was initiated soon after admission to emergency room in elderly patients who sustained osteoporotic proximal femoral fracture and who were considered to be high surgical risks. The severe pain was significantly reduced, enabling early mobilization of the patients. The analgesia was discontinued only when nonnarcotic analgesia sufficed. The treatment lasted for about 3.5 weeks. One minor complication was observed during the treatment period. We concluded that patients who have femoral neck fracture who are at high risk for operation and have to be observed and stabilized before operation can be managed by continuous epidural methadone analgesia. .A Nyska M; Shapira Y; Klin B; Drenger B; Margulies JY. .I 201551 .U 90009825 .S J Am Geriatr Soc 9001; 37(10):991-1002 .M Administration, Rectal; Aged; Aged, 80 and over; Bisacodyl/AD; Case Report; Fecal Incontinence/ET/*PP/TH; Human; Male; Patient Compliance; Physical Examination; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Fecal incontinence in an elderly man. Stanford University geriatrics case conference [clinical conference] .P JOURNAL ARTICLE. .A Goldstein MK; Brown EM; Holt P; Gallagher D; Winograd CH. .I 201552 .U 90009983 .S J Clin Gastroenterol 9001; 11(5):489-91 .M Abdominal Pain/ET; Human; Pancreas/*AB/SU; Pancreatic Ducts/*AB/SU; Pancreatic Function Tests; Pancreatitis/ET. .T Pancreas divisum--advocates and agnostics. .P JOURNAL ARTICLE. .W Pancreas divisum is discussed to define and evaluate criteria for treatment. Selecting candidates for surgery is imprecise since the anatomic anomaly is so prevalent. Endoscopic stenting has been utilized as a therapeutic and diagnostic test. Appraisals of operative results vary depending on length and detail of follow-up. Sphincteroplasty of the dorsal segment is the procedure of choice when the gland is normal--but resection and caudal drainage each have a role, depending on the anatomic and endoscopic findings. .A Cooperman AM; Siegel J; Hammerman H. .I 201553 .U 90009984 .S J Clin Gastroenterol 9001; 11(5):492-5 .M Campylobacter/PY; Campylobacter Infections/*CO; Gastric Mucosa/PH/SE; Gastritis/*MI; Human; Mucus/SE; Peptic Ulcer/*MI; Regeneration. .T Campylobacter pylori, mucus, and peptic ulceration. A dynamic interaction. .P JOURNAL ARTICLE. .W Campylobacter pylori, a spiral-shaped bacterium, commonly colonizes the gastric epithelium where it induces chronic gastritis; this organism has also been implicated in the etiology of chronic peptic ulcer disease. Once introduced to the gastric mucosa or an area of gastric metaplasia, it tends to migrate to the vicinity of the epithelial tight junction where it probably utilizes host urea and other substances to sustain itself. Campylobacter pylori also produces a proteolytic enzyme that degrades mucin. As the mucous layer slowly degrades, noxious luminal contents such as acid and pepsin have an opportunity to diffuse closer to the epithelium. We hypothesize that C. pylori, which is sensitive to low-pH environments, eventually migrates away from the compromised area to an area where the mucous layer is still protective. The injured epithelial focus left behind either regenerates its mucous layer and heals, or ulcerates depending upon the balance between other aggressive and protective factors. This interaction between C. pylori and the mucous layer is then repeated at the organism's new location. This hypothesis is consistent with existing data regarding C. pylori. It explains how C. pylori can be present in most duodenal ulcer patients and many gastric ulcer patients, as well as in otherwise healthy individuals. It also explains why ulceration is localized rather than diffuse when it does occur. .A Ormand JA; Talley NJ. .I 201554 .U 90009986 .S J Clin Gastroenterol 9001; 11(5):502-6 .M Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal/AE; Anti-Inflammatory Agents, Steroidal/AE; Comparative Study; Duodenal Ulcer/*DI/ET; Duodenoscopy; Female; Human; Male; Middle Age; Peptic Ulcer Hemorrhage/ET; Prospective Studies; Smoking/AE; Stomach Ulcer/DI. .T Duodenal ulcer in the elderly. .P JOURNAL ARTICLE. .W Of 333 duodenal ulcer (DU) patients 75 (22.5%) were aged 65-93 years (study group). Ninety-two percent (306 patients) of the entire group were diagnosed endoscopically, and all were followed prospectively. In the study group of the older patients there were fewer smokers, but more patients used steroids and other nonsteroidal antiinflammatory drugs (NSAIDs) and had more arteriosclerotic heart disease than the younger control group. Presenting signs and symptoms were similar in both age groups, although painless upper gastrointestinal bleeding was more common in the elderly, and pain, when present, tended to be milder. Bleeding episodes were more prevalent in the older age group. Another difference between the groups was the larger incidence of concurrent gastric ulcer and DU observed endoscopically in the study population. Steroids and NSAIDs could be etiologically connected to bleeding in the older patients, as well as to their relative lack of pain. We conclude that DU in the elderly tended to present atypically and that pain was not the major symptom of activity. This places a different emphasis on diagnostic and therapeutic criteria. .A Scapa E; Horowitz M; Waron M; Eshchar J. .I 201555 .U 90009987 .S J Clin Gastroenterol 9001; 11(5):507-10 .M Aged; Arteriovenous Malformations/*CO/SU; Electrocoagulation; Female; Gastric Mucosa/*BS; Gastrointestinal Hemorrhage/*ET/SU; Human; Male; Middle Age. .T Therapeutic endoscopy for Dieulafoy's disease. .P JOURNAL ARTICLE. .W Dieulafoy's disease is an underdiagnosed cause of massive upper gastrointestinal bleeding. The mortality rate is extremely high and the diagnosis is usually made at autopsy. Operation has been deemed the treatment of choice for Dieulafoy's disease in the past decades. Here, however, we report successful therapeutic endoscopy in eight cases of Dieulafoy's disease in a period of 20 months. Six patients (75%) were in shock before therapy. Six received heat-probe thermocoagulation, one received pure alcohol (99.8%) injection and one received hypertonic glucose solution (50%) injection. No perforation or recurrent hemorrhage occurred in the following period of 11.2 +/- 3.4 months (SEM) in six patients. The other two died of unrelated illness. In the near future, therapeutic endoscopy may replace surgery in the management of Dieulafoy's disease. .A Lin HJ; Lee FY; Tsai YT; Lee SD; Lee CH; Kang WM. .I 201556 .U 90009988 .S J Clin Gastroenterol 9001; 11(5):511-7 .M Adult; Aged; Case Report; Female; Follow-Up Studies; Gastroscopy; Human; Lymphoma/*/DI/PA; Male; Neoplasm Regression, Spontaneous/*; Stomach/*PA; Stomach Neoplasms/*/DI/PA; Time Factors. .T Spontaneous regression of primary malignant lymphoma of the stomach in two nontreated Japanese. .P JOURNAL ARTICLE. .W Two patients with primary malignant lymphoma underwent spontaneous regression. One was a 40-year-old woman with a large ulcerating tumor on the greater curvature of the gastric antrum. This tumor shrank spontaneously, leaving only a small shallow ulcer. The resected specimen showed a minute focus of malignant lymphoma in the ulcer base. The other was a 73-year-old man who had a tumor with central ulceration on the posterior wall of the gastric antrum. Endoscopic biopsy revealed a malignant lymphoma. This tumor disappeared 60 days later. The patient refused surgery and remains well with no evidence of recurrent disease at this writing, 44 months later. Although there have been several case reports of spontaneous regression, partial or complete, of gastric malignant lymphoma, our cases seem to be the ones best proven. .A Shigematsu A; Iida M; Lien GS; Imamura T; Okada M; Fuchigami T; Fujishima M; Itoh H; Iwashita A. .I 201557 .U 90009989 .S J Clin Gastroenterol 9001; 11(5):518-24 .M Adult; Aged; Caloric Intake; Female; Follow-Up Studies; Human; Malabsorption Syndromes/DI/*PP; Male; Middle Age; Nutritional Status; Postgastrectomy Syndromes/DI/*PP; Time Factors; Weight Loss. .T Malnutrition and malabsorption after total gastrectomy. A pathophysiologic approach. .P JOURNAL ARTICLE. .W We investigated the nutritional state and pathophysiologic mechanisms involved in the malabsorption of 27 patients with total gastrectomy and esophagojejunostomy reconstruction without reservoir; they were first evaluated after a median period of 9 months after surgery and were not receiving either nutritional or pharmacologic support. Mean postoperative weight loss was -13.7 +/- 1.59%; mean daily caloric intake was 31.7 +/- 2.41 kcal/kg/day, with 70% of subjects ingesting less than 30 kcal/kg; P/kg was 1.2 +/- 0.09, with 21% of patients ingesting less than 1 g P/kg/day; mean ratio of nonprotein energy to 1 g nitrogen intake was 142 +/- 8.74:1, with only 24% of patients attaining a ratio greater than 150:1; and mean fat malabsorption was 37.4 +/- 4.6%. Hemoglobin (Hb), serum albumin, prealbumin iron, and folate were more often abnormal in the early postoperative period, whereas transferrin and vitamin B12 concentrations deteriorated later. alpha 1-Antitrypsin clearance was abnormal in almost all patients (indicating an intestinal protein loss), and the pancreolauryl test was abnormal in 60%. Neither morphological nor absorptive alterations of the small bowel nor an abnormal transit time or bacterial overgrowth was found. We conclude that inadequate caloric intake appears to be the main cause for malnutrition after total gastrectomy, but that caloric losses caused by steatorrhea and enteric protein leakage must be subtracted from intake, thus decreasing the amount of available calories. .A Sategna-Guidetti C; Bianco L. .I 201558 .U 90009991 .S J Clin Gastroenterol 9001; 11(5):537-40 .M Adult; Aged; Aged, 80 and over; Female; Gallbladder/*PA; Gallbladder Diseases/*/ET/PA; Human; Periarteritis Nodosa/PA; Vasculitis/*/ET/PA. .T Gallbladder vasculitis. .P JOURNAL ARTICLE. .W Five cases of gallbladder vasculitis were encountered during a 10-year period in a community hospital with annual surgical cases of about 12,000. All five patients were clinically diagnosed as having cholelithiasis with or suspected to have cholecystitis. Vasculitis in the form of arteritis identical to that seen in polyarteritis nodosa was present microscopically in the cholecystectomy specimens. One patient presented with systemic symptoms, and the diagnosis of polyarteritis nodosa was established after arteritic lesions were identified in the cholecystectomy, liver biopsy, and appendectomy specimens. In another patient, the diagnosis of polyarteritis nodosa was established after a retrospective identification of one additional site of arteritis in the appendix removed 5 years prior to cholecystectomy. In another, gallbladder vasculitis was associated with scleroderma; the patient was studied thoroughly at autopsy shortly after cholecystectomy, and no evidence of polyarteritis nodosa was found. In the last two, gallbladder vasculitis was not associated with systemic diseases. .A Chen KT. .I 201559 .U 90009993 .S J Clin Gastroenterol 9001; 11(5):546-51 .M Adult; Cholestasis, Intrahepatic/*/DI/TH; Cholestyramine/TU; Female; Human; Male; Phenobarbital/TU; Plasmapheresis; Recurrence. .T Benign recurrent intrahepatic cholestasis. A report of 26 cases. .P JOURNAL ARTICLE. .W Benign recurrent intrahepatic cholestasis is characterized by attacks of cholestasis. The purpose of our study of 26 patients was to emphasize some features uncommonly or never reported in this disease: (a) in each patient, the attacks of cholestasis were stereotypic; (b) attacks of cholestasis were not associated with pruritus in 15% of our patients; (c) the occurrence of attacks of cholestasis during pregnancy or oral contraceptive use might be a fortuitous coincidence; (d) gallstones were found in several patients with benign recurrent intrahepatic cholestasis and might be present earlier than in the general population; (e) in some of our patients, during attacks of cholestasis, serum transaminases were very high, exceeding 15 times the upper limit of normal; (f) mild portal inflammatory infiltration was found in one third of our patients; (g) no treatment shortened the duration of cholestasis, and in a few patients, plasmapheresis seemed to diminish jaundice and improve biochemical disorders. .A Brenard R; Geubel AP; Benhamou JP. .I 201560 .U 90009994 .S J Clin Gastroenterol 9001; 11(5):552-4 .M Adult; Aeromonas; Bacterial Infections/CO/*DT; Case Report; Ciprofloxacin/*TU; Colitis/CO/*DT; Human; HIV Seropositivity/*CO; Male; Opportunistic Infections/CO/*DT. .T Treatment with ciprofloxacin of Aeromonas hydrophila associated colitis in a male with antibodies to the human immunodeficiency virus. .P JOURNAL ARTICLE. .W A 36-year-old white male intravenous drug abuser and homosexual, with antibodies in the serum to the human immunodeficiency virus and a history of ulcerative colitis, had bloody diarrhea and spiking fevers that did not respond to treatment for 1 month with total parenteral nutrition, orally administered sulfasalazine, and 5-amino-salicylic acid enema. Aeromonas hydrophila was isolated from bacterial culture of a biopsy specimen obtained by sigmoidoscopy. The symptoms resolved after a 2 week course of treatment with orally administered ciprofloxacin. Although ciprofloxacin has been reported to be effective against Aeromonas hydrophila in vitro, this is the first report of successful treatment of Aeromonas-associated colitis with ciprofloxacin. .A Liao WC; Cappell MS. .I 201561 .U 90009995 .S J Clin Gastroenterol 9001; 11(5):555-60 .M Carcinoma, Scirrhous/*SC; Case Report; Colon/PA; Colonic Neoplasms/PA/RA/*SC; Crohn Disease/*RA; Diagnosis, Differential; Female; Human; Linitis Plastica/PA/RA/*SC; Middle Age; Stomach Neoplasms/*. .T Gastric linitis plastica with metastases to the colon: a mimic of Crohn's disease. .P JOURNAL ARTICLE. .W A 60-year-old woman had progressive lower abdominal pain, nonbloody diarrhea, and weight loss, followed by severe epigastric pain and dysphagia. Radiographic evaluation of the colon showed segmental strictures which were interpreted as Crohn's disease. Medical treatment was not helpful. Neither gross endoscopic appearance nor multiple biopsies of the esophagus, stomach, and colon were diagnostic. Finally, laparotomy with full-thickness biopsies of the stomach and colon revealed linitis plastica. The clinician should be alert to colonic metastases from gastric linitis plastica, for it can produce focal or segmental strictures, mimicking more common colonic diseases such as Crohn's disease. A full-thickness biopsy is often necessary for a firm diagnosis. We review the literature on this occurrence, highlighting the clinical and radiologic spectrum, as well as the organ systems most often affected when gastric linitis plastica metastasizes. .A Katon RM; Brendler SJ; Ireland K. .I 201562 .U 90009996 .S J Clin Gastroenterol 9001; 11(5):561-4 .M Adult; Candidiasis, Cutaneous/*DI; Case Report; Diagnosis, Differential; Ear, External/*; Female; Human; Inflammatory Bowel Diseases/CO; Pyoderma/CO/*DI; Skin Ulcer/CO/*DI; Time Factors. .T Atypical auricular pyoderma gangrenosum simulating fungal infection. .P JOURNAL ARTICLE. .W We describe a patient with a highly unusual appearance of pyoderma gangrenosum. The pyoderma was located on the auricular region and preceded other manifestations of inflammatory bowel disease by 11 years. There was no correlation between the course of the pyoderma and the clinical activity of the associated bowel disease. Mycotic superinfections masked and delayed the diagnosis in our patient for several years. Only when typical pyoderma gangrenosum lesions developed on the legs at the site of trauma and responded dramatically to systemic corticosteroids was the correct diagnosis established. Pyoderma gangrenosum with secondary fungal infection was thus distinguished from deep ulcerated skin fungal infection simulating pyoderma. .A Lysy J; Zimmerman J; Ackerman Z; Reifen E. .I 201563 .U 90009997 .S J Clin Gastroenterol 9001; 11(5):565-7 .M Adenocarcinoma/*PA; Aged; Biopsy; Bone Marrow/PA; Case Report; Colon/PA; Colonic Neoplasms/*PA; Human; Male; Multiple Myeloma/*PA; Neoplasms, Multiple Primary/*PA. .T Aggressive behavior of carcinoma of the colon associated with nonsecreting plasma cell myeloma. A case report. .P JOURNAL ARTICLE. .W A patient was diagnosed for nonsecreting myeloma stage IIIA (Salmon-Durie) 6 months after colectomy for adenocarcinoma of the colon, Duke's stage A. The patient had not received chemotherapy for the colonic carcinoma and its clinical course was much more aggressive than expected. Although it might be coincidental, to our knowledge this is the first reported case of an association between a nonsecreting myeloma and adenocarcinoma of the colon. .A Yermiahu T; Peiser J; Benharroch D; Ovnat A. .I 201564 .U 90009998 .S J Clin Gastroenterol 9001; 11(5):568-70 .M Aged; Alcoholism/*CO; Ascites/ET; Ascitic Fluid/*; Case Report; Human; Infusions, Intravenous; Male; Pancreatitis/ET/*TH. .T Treatment of alcoholic pancreatic ascites by intravenous infusion of ascitic fluid. .P JOURNAL ARTICLE. .W Pancreatic ascites is usually due to a major duct disruption and responds best to surgery. Reported here is a favorable outcome of chronic ascites in an elderly, frail alcoholic treated by paracentesis and intravenous reinfusion of ascitic fluid. .A Giaffar MH; Isaacs PE. .I 201565 .U 90009999 .S J Clin Gastroenterol 9001; 11(5):571-3 .M Adult; Bile/*; Biliary Tract/RI; Biopsy, Needle/*AE; Case Report; Culdoscopy; Female; Human; Liver/*PA; Peritonitis/*DI/ET. .T Scintigraphic and culdoscopic diagnosis of bile peritonitis complicating liver biopsy. .P JOURNAL ARTICLE. .W After an ultrasound-guided percutaneous liver biopsy, a 37-year-old woman developed a clinical syndrome suggestive of bile peritonitis, despite the presence of nondilated bile ducts and a surgically absent gallbladder. The diagnosis was established via hepatobiliary scintigraphy, which demonstrated aberrant biliary flow, as well as by culdocentesis, which yielded bilious fluid. The patient was managed medically and recovered uneventfully; follow-up biliary scanning established resolution of bile extravasation. .A Veneri RJ; Gordon SC; Fink-Bennett D. .I 201566 .U 90010000 .S J Clin Gastroenterol 9001; 11(5):574-7 .M Ascites/ET/TH; Bile/*; Case Report; Cholecystectomy/*AE; Drainage/*MT; Female; Human; Intubation, Gastrointestinal/*; Middle Age. .T Closure of cystic duct stump leak by nasobiliary tube drainage. .P JOURNAL ARTICLE. .W We report a case of symptomatic bile ascites persisting 6 weeks after cholecystectomy from a cystic stump leak. We describe the successful endoscopic treatment of post-cholecystectomy bile ascites using a nasobiliary drain and propose this method of treatment as an alternative to surgical intervention and external drainage in selected cases. .A Barthel JS; Sastri SV; Landsbaum C. .I 201567 .U 90010001 .S J Clin Gastroenterol 9001; 11(5):578-83 .M Bile Duct Neoplasms/PA/*SC; Bile Ducts/PA; Case Report; Cholestasis/*ET; Hepatoma/*CO/PA; Human; Liver/PA; Liver Neoplasms/*CO/PA; Male; Middle Age. .T Small hepatocellular carcinoma presenting as intrabiliary pedunculated polyp and obstructive jaundice. .P JOURNAL ARTICLE. .W A rare autopsy case of small hepatocellular carcinoma presenting as an intrabiliary pedunculated mass is reported. The patient, 60-year-old man, presented with obstructive jaundice and died 1 month later. At autopsy, an intrabiliary pedunculated tumor measuring 3.5 x 2.0 x 2.0 cm was found in the hepatic, right hepatic, and right posterior segmental bile ducts. The intraductal tumor was attached to the segmental bile ductal wall, where a tumor measuring 2.0 x 0.9 cm was found in the parenchyma. The parenchymal tumor was continuous with the intrabiliary mass. Histologically, the tumor was a hepatocellular carcinoma showing acidophilic granular cytoplasm with occasional hyaline globules and was structurally arranged in a vague trabecular pattern. Immunohistochemically, tumor cells were positive for alpha-fetoprotein and alpha 1-antitrypsin, but was negative for keratin. We present a brief review of the literature of such icteric hepatocellular carcinomas. .A Terada T; Nakanuma Y; Kawai K. .I 201568 .U 90010002 .S J Clin Gastroenterol 9001; 11(5):584-5 .M Anemia, Pernicious/*ET; Campylobacter Infections/*CO; Gastritis/*ET; Human. .T Is pernicious anemia caused by Campylobacter pylori gastritis? [letter] .P LETTER. .A DeLuca VA Jr. .I 201569 .U 90010003 .S J Clin Gastroenterol 9001; 11(5):585 .M Adult; Campylobacter/*IP; False Negative Reactions; Formaldehyde/*; Human; Male; Tissue Preservation/*. .T Histological evaluation of Campylobacter pylori from tissue specimens stored in formaldehyde can be misleading [letter] .P LETTER. .A Fich A; Talley NJ; Shorter RG; Phillips SF. .I 201570 .U 90010005 .S J Clin Gastroenterol 9001; 11(5):587-8 .M Duodenal Ulcer/*EP; Human; Israel/EP; Seasons/*. .T High winter incidence of duodenal ulcer in Israel [letter; comment] .P COMMENT; LETTER. .A Slater PE. .I 201571 .U 90010006 .S J Clin Gastroenterol 9001; 11(5):588-90 .M Aged; Breast Neoplasms/*; Case Report; Esophageal Motility Disorders/*ET; Esophageal Neoplasms/CO/*SC; Female; Human; Time Factors. .T Late recurrence of breast cancer presenting with esophageal dysmotility. .P JOURNAL ARTICLE. .A Isaacs P; MacGillivray N; Springett P. .I 201572 .U 90010007 .S J Clin Gastroenterol 9001; 11(5):590-1 .M Adult; Aged; Female; Gastroesophageal Reflux/*CO; Human; Male; Middle Age; Sweating/*. .T Are night sweats a sign of esophageal reflux? .P JOURNAL ARTICLE. .A Reynolds WA. .I 201573 .U 90010008 .S J Clin Gastroenterol 9001; 11(5):591-2 .M Adenocarcinoma/SU; Carcinoma, Squamous Cell/SU; Esophageal Neoplasms/*SU; Female; Human; Laser Surgery/*; Male; Middle Age; Palliative Treatment/*MT. .T The William Beaumont Army Medical Center experience with endoscopic neodymium: YAG laser palliative therapy of esophagogastric cancer [letter] .P LETTER. .A Burkhalter E. .I 201574 .U 90010009 .S J Clin Gastroenterol 9001; 11(5):592-4 .M Aged; Case Report; Cysts/*CO; Female; Human; Hypertension, Portal/ET; Liver/PA; Liver Diseases/*CO. .T Adult polycystic liver presenting with progressive hepatic failure [letter] .P LETTER. .A Nakanuma Y; Hoso M; Hayashi M; Hirai N. .I 201575 .U 90010010 .S J Clin Gastroenterol 9001; 11(5):594-6 .M Carcinoma/*DI; Case Report; Diagnosis, Differential; Human; Lymphoma/*DI; Male; Middle Age; Pancreas/PA; Pancreatic Neoplasms/*DI. .T Pancreatic involvement by lymphoma simulates pancreatic carcinoma [letter] .P LETTER. .A Kondo T; Hayakawa T; Shibata T; Kitagawa M; Nimura Y; Hayakawa N; Kanda S. .I 201576 .U 90010011 .S J Clin Gastroenterol 9001; 11(5):596-7 .M Adult; Case Report; Common Bile Duct Calculi/*ET; Female; Hemostasis, Surgical/*IS; Human; Iatrogenic Disease/*; Pancreatitis/*ET. .T An iatrogenic gallstone with pancreatitis [letter] .P LETTER. .A Farr CM; Larson C; Gladen HE; Witherspoon L; Lesperance R; Moseley D. .I 201577 .U 90010012 .S J Clin Gastroenterol 9001; 11(5):597-8 .M Colorectal Neoplasms/*BL; Glycoproteins/*BL; Human; Neoplasm Proteins/*BL; Tumor Markers, Biological/*BL. .T Prognostic significance of immunosuppressive substance in the sera of colorectal cancer patients [letter] .P LETTER. .A Suzuki H; Matsumoto K; Matsumoto K. .I 201578 .U 90010013 .S J Clin Gastroenterol 9001; 11(5):598-9 .M Case Report; Colon/PA; Colonic Neoplasms/*DI; Human; Lymphangioma/*DI; Male; Middle Age. .T Lymphangioma of the ascending colon [letter] .P LETTER. .A Yamamoto J; Matsumoto K; Furuya T. .I 201579 .U 90010014 .S J Clin Gastroenterol 9001; 11(5):599-601 .M Biopsy, Needle/*MT; Case Report; Hepatoma/*PA; Human; Liver/*PA; Liver Neoplasms/*PA; Male; Microscopy, Electron; Middle Age. .T Fine needle aspiration with Menghini needle biopsy. .P JOURNAL ARTICLE. .A Kahn S; Thomas E; Farnum JB. .I 201580 .U 90010015 .S J Clin Gastroenterol 9001; 11(5):601-2 .M Campylobacter Infections/DT; Clindamycin/*PK/TU; Gastric Mucosa/*DE; Human. .T Clindamycin secretion across human gastric mucosa [letter] .P LETTER. .A Duriex DE; Westblom TU. .I 201581 .U 90010016 .S J Clin Gastroenterol 9001; 11(5):602-3 .M Adult; Amodiaquine/*AE/TU; Case Report; Female; Hepatitis, Toxic/*ET; Human; Malaria/PC. .T Fatal acute hepatitis due to amodiaquine [letter] .P LETTER. .A Raymond JM; Dumas F; Baldit C; Couzigou P; Beraud C; Amouretti M. .I 201582 .U 90010017 .S J Clin Gastroenterol 9001; 11(5):603-5 .M Celiac Disease/*CO; Human; Male; Middle Age; Nervous System Diseases/*ET; Vitamin E Deficiency/*CO. .T Neurological manifestations in celiac disease and vitamin E deficiency [letter] .P LETTER. .A Ackerman Z; Eliashiv S; Reches A; Zimmerman J. .I 201583 .U 90010018 .S J Clin Gastroenterol 9001; 11(5):605 .M Diagnostic Tests, Routine/*; Human; Occult Blood/*. .T Hemocult testing should be done routinely, not abandoned: reply to Dr. Longstreth [letter; comment] .P COMMENT; LETTER. .A Varner AA. .I 201584 .U 90010106 .S J Immunol 9001; 143(8):2431-8 .M Animal; Antigens, Surface/*; Bone Marrow/*PH; Cell Differentiation; Dendritic Cells/IM/*PH; Epidermis/IM/*PH; Female; Fetus; Histocompatibility Antigens Class II/ME; Kinetics; Langerhans Cells/IM/*PH; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Phenotype; Stem Cells/IM/PH; Support, Non-U.S. Gov't. .T Maturational steps of bone marrow-derived dendritic murine epidermal cells. Phenotypic and functional studies on Langerhans cells and Thy-1+ dendritic epidermal cells in the perinatal period. .P JOURNAL ARTICLE. .W The adult murine epidermis harbors two separate CD45+ bone marrow (BM)-derived dendritic cell systems, i.e., Ia+, ADPase+, Thy-1-, CD3- Langerhans cells (LC) and Ia-, ADPase-, Thy-1+, CD3+ dendritic epidermal T cells (DETC). To clarify whether the maturation of these cells from their ill-defined precursors is already accomplished before their entry into the epidermis or, alternatively, whether a specific epidermal milieu is required for the expression of their antigenic determinants, we studied the ontogeny of CD45+ epidermal cells (EC). In the fetal life, there exists a considerable number of CD45+, Ia-, ADPase+ dendritic epidermal cells. When cultured, these cells become Ia+ and, in parallel, acquire the potential of stimulating allogeneic T cell proliferation. These results imply that CD45+, Ia-, ADPase+ fetal dendritic epidermal cells are immature LC precursors and suggest that the epidermis plays a decisive role in LC maturation. The day 17 fetal epidermis also contains a small population of CD45+, Thy-1+, ADPase-, CD3- round cells. Over the course of 2 to 3 wk, they are slowly replaced by an ever increasing number of round and, finally, dendritic CD45+, Thy-1+, CD3+ EC. Thus, CD45+, Thy-1+, ADPase-, CD3- fetal EC may either be DETC precursors or, alternatively, may represent a distinctive cell system of unknown maturation potential. According to this latter theory, these cells would be eventually outnumbered by newly immigrating CD45+, Thy-1+, CD3+ T cells--the actual DETC. .A Elbe A; Tschachler E; Steiner G; Binder A; Wolff K; Stingl G. .I 201585 .U 90010107 .S J Immunol 9001; 143(8):2439-47 .M Adjuvants, Immunologic/PH; Adult; Antibodies, Monoclonal/*PH; Antigens, Differentiation, T-Lymphocyte/*IM; Cell Adhesion; Cells, Cultured; Human; Interleukin-2/PH; Lymphocyte Transformation/*; Middle Age; Monocytes/IM; Phenotype; Receptors, Antigen, T-Cell/PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; T-Lymphocytes/*IM/PH. .T Anti-T12, an anti-CD6 monoclonal antibody, can activate human T lymphocytes. .P JOURNAL ARTICLE. .W Anti-T12 is a murine IgM mAb that recognizes the 130-kDa CD6 glycoprotein on mature human T lymphocytes. Examination of the in vitro effects of this mAb on freshly isolated T cells demonstrates that anti-T12 can induce T cell activation. Such activation is macrophage-dependent, and optimal stimulation occurs with 0.2 to 5 micrograms/ml of purified mAb. This response to soluble mAb is detectable at day 4 to 5 of culture, and peak [3H]TdR uptake is observed at day 7. In a highly similar fashion, the mAb causes a marked augmentation of the autologous mixed lymphocyte reaction, without altering the kinetics of that response. Although optimal anti-CD3 mAb induced mitogenesis is unaffected by anti-T12, suboptimal stimulation of macrophage-depleted T cells by small amounts of immobilized anti-CD3 can be dramatically enhanced when anti-CD3 and anti-T12 are cross-linked together. A soluble nonmitogenic anti-CD3 mAb completely inhibits anti-T12-mediated T cell activation. IL-2R expression is induced by anti-T12 stimulation in 10 to 30% of T cells, and T cell proliferation is substantially inhibited by anti-IL-2R mAb, indicating that anti-T12 induced T cell activation and proliferation utilizes an IL-2-dependent pathway. Isolated CD4+ but not CD8+ cells are stimulated to proliferate, but the CD8+ cells in unseparated T cell preparations activated by anti-T12 do proliferate comparably to the CD4+ cells in such cultures. These data indicate that relatively weak activation of T cells via the TCR/CD3 complex may be augmented significantly by CD6-mediated signals induced by the anti-T12 mAb. The findings suggest that the CD6 T cell membrane protein may have the capacity to function as a physiologically important structure involved in the regulation of T cell activation. .A Gangemi RM; Swack JA; Gaviria DM; Romain PL. .I 201586 .U 90010109 .S J Immunol 9001; 143(8):2452-6 .M Animal; Antigenic Determinants/*IM; Epidermis/*IM; Graft Rejection/*; Histocompatibility Antigens Class II/*IM; Isoantigens/IM; Langerhans Cells/IM; Mice; Mice, Inbred A; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Nude; Skin Transplantation/*IM; T-Lymphocytes, Cytotoxic/IM; T4 Lymphocytes/*IM. .T Rejection of skin allografts by CD4+ T cells is antigen-specific and requires expression of target alloantigen on Ia- epidermal cells. .P JOURNAL ARTICLE. .W The effector mechanism of skin allograft rejection has been characterized as Ag specific, rejecting cells that express the target alloantigen but sparing those that do not. However, the rejection of MHC class II disparate skin grafts, in which very few cells (Langerhans cells) actually express the target Ia Ag could conceivably proceed by either one of two distinct rejection mechanisms. One possibility is that Ia- cells are destroyed by a sequence of events in which CD4+ T cells, activated by Ia+ LC, elaborate soluble factors that are either directly cytolytic or that recruit and activate non-specific effector cells. The alternative possibility is that activated CD4+ T cells elaborate soluble factors which induce Ia expression on Ia- cell populations, and that these Ia+ cells are subsequently destroyed by effector cells specific for the induced Ia alloantigens. We found that rejection of Ia+ LC was not of itself sufficient to cause rejection of skin grafts, indicating that skin allograft rejection is contingent on the destruction not only of LC but of other graft cell populations as well. We then investigated whether CD4+ T cells rejected allogeneic skin grafts in an antigen specific fashion. To do so, we engrafted immunoincompetent H-2b nude mice with trunk skin grafts from B6----A/J allophenic mice because such skin is composed of mutually exclusive cell populations expressing either H-2a or H-2b histocompatibility Ag, but not both. The engrafted mice were subsequently reconstituted with H-2b CD4+ T cells. The CD4+ T cells destroyed keratinocytes of A/J origin but spared keratinocytes of B6 origin, even though neither cell population constitutively expresses target IAk alloantigen. The targeted rejection of A/J keratinocytes but not of B6 keratinocytes indicates that the target Ia alloantigen must have been induced on Ia- A/J keratinocytes, rendering them susceptible to destruction by anti-Iak-specific CD4+ effector cells. These data demonstrate that CD4+ T cell rejection of skin allografts is mediated by Ag-specific CD4+ cytolytic T cells and hence, requires the induction of target Ia alloantigens on epidermal cells within the graft. .A Rosenberg AS; Katz SI; Singer A. .I 201587 .U 90010111 .S J Immunol 9001; 143(8):2464-9 .M Adult; Antibody Diversity/*; B-Lymphocytes/IM/ME/PH; Bone Marrow/*IM/ME/PH; Cell Differentiation; Cell Line, Transformed; Fetal Development/*; Hematopoietic Stem Cells/IM/ME/PH; Human; Immunoglobulin Isotypes/*BI/CL/PH; Phenotype; Support, Non-U.S. Gov't. .T Concerted generation of Ig isotype diversity in human fetal bone marrow. .P JOURNAL ARTICLE. .W The human fetal bone marrow B cell compartment of 14- to 21-wk gestational age was examined phenotypically and with respect to Ig H chain commitment and diversity. A dramatic expansion of fetal marrow B cell pools at 16- to 18-wk gestational age characterizes a rapid and concerted chain of differentiation events. Transiently up to 1/4 of nucleated marrow cells are CD20+/CD21+ cells which begin to express surface Ig other than IgM. Limiting dilution analysis of EBV-infected marrow cells delineated a virtually exclusive commitment to IgM production until 15 wk and the absolute and relative number of these cells were small (approximately 5% of comparable adult values). In parallel to the rapid increase in total B cell pools size, cells committed and able to secrete any of the five Ig isotypes are generated by 16-wk gestational age and by 18 wk the frequencies of these cells rapidly reach levels typical for adult peripheral tissue such as blood or lymph node. Fetal L chain diversity always anticipated that observed in adult serum. In addition to rising pool sizes and diverse IgH expression, EBV transformability is a major variable during this period of B cell development with up to 2/3 of B lineage cells transformable, about half of which are pre-B cells. By 21-wk gestational age transformable pre-B cells have disappeared and (as in adult tissue) approximately 10 to 20% of CD20+ cells are transformable. The rapid, concerted expression of full H chain diversity during a narrow period in fetal development is unique to marrow and implies a lymphopoietic process in a privileged site rather than an immunologic differentiation event. During this event, the relative proportions between the different IgH classes expressed, resembled that found in adult tissue, perhaps suggesting that B cell inherent programming rather than only antigenic forces determine heavy chain choice. The staggered expression, early in postnatal life, of IgH regions 3' of the C mu locus may reflect regulatory functions rather than inherent immaturity of the B lineage. .A Dosch HM; Lam P; Hui MF; Hibi T. .I 201588 .U 90010112 .S J Immunol 9001; 143(8):2470-9 .M B-Lymphocytes/IM/ME/*PH; Cell Differentiation; Cell Division; Cell Line, Transformed; Cell Transformation, Viral/*; Clone Cells/IM/ME/PH; Epstein-Barr Virus/*PH; Fetal Development/*; Gene Rearrangement, B-Lymphocyte; Genes, Immunoglobulin; Hematopoietic Stem Cells/IM/ME/*PH; Human; Phenotype; Support, Non-U.S. Gov't. .T Properties and heterogeneity of human fetal pre-B cells transformed by EBV. .P JOURNAL ARTICLE. .W A series of 75 EBV-transformed pre-B and B-cell lines from fetal bone marrow at 14 to 18 wk of gestation was cloned for phenotypic, functional and molecular genetic studies. B-cell type volume regulation in response to hypotonic stress, low level CD9 (BA2), and, perhaps biased by our use of EBV, functional EBV receptors with expression of CD21 (B2) determinants characterized the most immature cells detected. These "B-progenitors" contained EBV genomes, maintained Ig H and L chain (as well as TCR) constant region genes in germ-line configuration and did not express other B, T, or myeloid lineage-associated surface markers including CD20 and MHC class II determinants. Such cells may represent B progenitor cells preceding classical pre-B-lymphocytes in pathways of B cell differentiation. Reminiscent of Abelson virus-induced transformation of immature murine B cells, EBV transformability together with the above properties may be the earliest markers of B lineage commitment in man. The expression of MHC class II Ag, CD20, C mu-H and then L chain rearrangements and expression followed in less immature pre-B lymphocytes and permitted a classification of lines into discrete subgroups of increasing maturity. The physical organization of the H chain locus in a given line was a stable characteristic. However, fetal pre-B cell lines showed considerable intraclonal heterogeneity with respect to H chain gene expression and that of differentiation markers such as CD20. Subcloning experiments indicated that this heterogeneity reflected clonally stable expression patterns distributed among subclones in an all-or-none fashion. The induction, by IL-6, of L chain expression in some but not all of these clones was linked to the presence of C mu transcription products, consistent with a possible regulatory role of mu protein in L chain rearrangement and expression. Although pre-B cell differentiation likely follows inherent programming, external signals seem able to hasten development along prescribed, hierarchical differentiation pathways. .A Hui MF; Lam P; Dosch HM. .I 201589 .U 90010113 .S J Immunol 9001; 143(8):2480-8 .M Antibodies, Monoclonal; Child; Human; Immunohistochemistry; Lymphoma/AN/PA; Receptors, Antigen, T-Cell/*AN; Spleen/ME/PA; Stains and Staining; Support, Non-U.S. Gov't; T-Lymphocytes/*ME/PA; Thymus Gland/ME/PA; Tonsil/ME/PA. .T Distribution of T cells bearing different forms of the T cell receptor gamma/delta in normal and pathological human tissues. .P JOURNAL ARTICLE. .W Frozen sections from normal and pathologic human tissues were immunostained by the APAAP technique with three mAb directed against different epitopes of the TCR gamma delta; TCR delta 1 which binds to all cells bearing the TCR gamma delta; BB3 and delta TCS1 which, by immunoprecipitation studies, appear to react respectively with the disulfide-linked and nondisulfide-linked form of the TCR gamma delta. In normal thymus, TCR delta 1+ cells accounted for approximately 2% of the CD3+ thymocytes and were about three times more numerous in the medulla than in the cortex. TCR delta 1+ cells were mostly constituted by the delta TCS1 reactive subset (average ratio delta TCS1/BB3: 3.7). In the tonsil, the TCR delta 1+ cells (about 3% of CD3+ elements) were mainly located in the interfollicular area, where they frequently tended to arrange around high endothelium venules. In most samples, TCR delta 1+ cells were distributed beneath to the tonsil epithelium. Unlike thymus, the majority of TCR delta 1+ cells were usually constituted by the BB3-reactive subset (average BB3/delta TCS1 ratio: 2.0). A similar predominance of BB3+ over delta TCS1+ cells was also observed in normal peripheral blood. The spleen was the organ with the highest concentration of TCR delta 1+ cells that, like in the thymus, were mostly represented by delta TCS1+ elements. Noteworthy, the TCR delta 1+ cells were preferentially located in the splenic sinusoids while TCR alpha beta-bearing lymphocytes mostly occupied the periarteriolar sheaths of penicilliary arteries. The majority of neoplastic T cell proliferations studied lacked to express the TCR gamma delta. Two cases of beta F1-(TCR alpha beta-) T lymphoblastic lymphoma, however, were TCR gamma delta+ (delta TCS1+/BB3-). Both of them showed a stage II cortical phenotype, e.g., CD1+/CD3+/CD4+/CD8+/TCR delta 1+. Among inflammatory conditions, an increase of BB3+ cells was observed in close association with necrotic areas in cases of Kikuchi's and tuberculous lymphadenitis. The significance of this finding is under study. .A Falini B; Flenghi L; Pileri S; Pelicci P; Fagioli M; Martelli MF; Moretta L; Ciccone E. .I 201590 .U 90010114 .S J Immunol 9001; 143(8):2489-93 .M Acute Disease; Animal; Cells, Cultured; Chronic Disease; Crosses, Genetic; Female; Graft vs Host Disease/ET/GE/*IM; Lymphocytes/*TR; Male; Mice; Mice, Inbred AKR; Mice, Inbred C57BL; Mice, Inbred DBA; Species Specificity; Spleen/TR; Support, U.S. Gov't, P.H.S.. .T DBA/2J and DBA/2Ha lymphocytes differ in their ability to induce graft-vs-host disease. .P JOURNAL ARTICLE. .W Graft-vs-host disease (GVHD) is a common occurrence after bone marrow transplantation despite the use of MHC-matched donors and recipients. This indicates that non-MHC loci play an important role in the regulation and development of GVHD. Non-MHC loci have been shown to regulate GVHD in a murine model where acute GVHD results from i.v. injection of C57BL/6J spleen cells into B6D2F1/J [C57BL/6J X DBA/2J)F1) recipients while chronic GVHD results from injection of DBA/2J spleen cells. In contrast to the hyperproduction of Ig and auto-antibodies that is characteristic of the chronic GVHD that occurs after injection of DBA/2J cells, injection of DBA/2Ha cells was found to induce CTL and suppressor cells characteristic of the acute GVHD that results from injection of C57BL/6 cells into B6D2F1/J recipients. Genetic analysis indicated that one autosomal locus is responsible for the different GVHD responses of DBA/2J and DBA/2Ha cells and that the DBA/2Ha allele is dominant. Further studies indicate that the different responses by DBA/2J and DBA/2Ha cells is not due to functional differences between the two sets of cells but by a radiosensitive B6D2F1 recipient immune response which discriminates between the DBA/2J and DBA/2Ha spleen cells. .A Fast LD. .I 201591 .U 90010116 .S J Immunol 9001; 143(8):2501-7 .M Antibodies, Anti-Idiotypic/PH; Antibodies, Monoclonal/PH; Antigenic Determinants/AN; B-Lymphocytes/IM/*ME/MI; Blotting, Southern; Cell Division; Cell Line, Transformed; Cell Transformation, Viral; Clone Cells/IM/ME/MI; Human; HTLV-I/*IM/ME/PH; HTLV-I Infections/*ME; IgM/*BI/IM/PH; Immunoglobulin Idiotypes/IM; Molecular Weight; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Viral Proteins/*IM/ME; Virion/PH. .T IgM secreted by human T lymphoma virus-I-infected and transformed human B cell clones recognize a 66-kilodalton host-encoded protein. .P JOURNAL ARTICLE. .W It has previously been determined that transformed human B cells may be infected by and retain integrated human T cell lymphotropic virus, type I (HTLV-I). Although HTLV-I is primarily associated with transformation of human T lymphocytes, immortalized B cell populations have arisen after cocultivation of normal B cells and irradiated HTLV-I-infected T cells. To test whether HTLV-I infection might be involved in this B cell transformation process, we characterized five independent HTLV-I-infected and -immortalized human B cell clones. All five clones contained clonal HTLV-I integrations, expressed cell surface IgM, and secreted IgM in quantities varying from 0.1 to 4.0 micrograms/ml. Immunoblotting and immunoprecipitation of metabolically labeled cell lysates failed to detect synthesis of HTLV-I gag, env, or tat gene products, and cellular RNA dot blot analysis detected varying levels of HTLV-I gene transcripts in only three of the five clones. The secreted IgM from culture supernatants were affinity purified, and were found to selectively immunoprecipitate an acidic protein (isoelectric point = 5.0) of 66,000 m.w. (p66) from purified radioiodinated HTLV-I virions. This p66 copurified with metabolically labelled HTLV-I-infected B cell IgM from HKA-3 cells. Although HTLV-I RNA transcripts were present at low levels, the absence of HTLV-I proteins in HKA-3 cells made it unlikely that p66 was related to the major HTLV-I envelope glycoprotein, gp62. Anti-idiotypic mAb directed against the IgM produced by one B cell clone (HKA-3), as well as purified HTLV-I virions (containing p66), stimulated HKA-3 cell proliferation. Preincubating the anti-Id antibody or HTLV-I with excess HKA-3 IgM abolished the binding of either to HKA-3 cells. These data suggest that HTLV-I infected cells produce a cellular protein (p66), which is incorporated into and copurifies with HTLV-I virions, and which in at least one case (HKA-3) may act as a mitogenic stimulus, potentially contributing to the HTLV-I mediated transformation process. .A Ng VL; Rainer C; Oliver MR; Marsh J; Wood P; Reyes GR; McGrath MS. .I 201592 .U 90010117 .S J Immunol 9001; 143(8):2508-13 .M Adjuvants, Immunologic/PH/TU; Animal; Antibodies, Anti-Idiotypic/BI/PH/*TU; Antibodies, Monoclonal/BI/PH/*TU; Cryoglobulinemia/IM/PA/*PC; Cryoglobulins/ME; Glomerulonephritis/PA; IgG/PH; Immunoglobulin Idiotypes/*IM; Mice; Mice, Inbred BALB C; Precipitin Tests; Rheumatoid Factor/PH; Skin/PA; Support, Non-U.S. Gov't. .T Prevention of murine cryoglobulinemia and associated pathology by monoclonal anti-idiotypic antibody. .P JOURNAL ARTICLE. .W A murine IgG3 mAb, clone 6-19, derived from non-manipulated autoimmune MRL/MpJ-lpr/lpr mice is a rheumatoid factor specific for IgG2a and is able to generate cryoglobulins via nonspecific IgG3 Fc-Fc interaction. Intraperitoneal passive transfer of ascites containing the 6-19 mAb into BALB/c mice induces, within 18 h, remarkable pathology characterized by skin vasculitis and acute glomerulonephritis associated with cryoglobulinemia. In order to evaluate the possibility of modulating the development of tissue lesions by an anti-Id antibody, we have raised an IgG2b anti-Id mAb specific to the 6-19 mAb. The cryoprecipitation of 6-19 mAb was completely inhibited in the presence of excess amounts of anti-Id mAb in vitro. In vivo, pretreatment of BALB/c mice with anti-6-19 anti-Id mAb inhibited development of skin vasculitis and glomerulonephritis induced by the 6-19 mAb. The cryoglobulin formation was markedly diminished due to enhanced elimination of the 6-19 mAb from the circulation. In contrast, pretreatment with an IgM anti-IgG3 rheumatoid factor mAb neither protected nor aggravated the development of tissue lesions. These results suggest possible implications in the anti-Id treatment of similar vascular diseases in man. .A Spertini F; Donati Y; Welle I; Izui S; Lambert PH. .I 201593 .U 90010118 .S J Immunol 9001; 143(8):2514-9 .M Adjuvants, Immunologic/PH; Animal; Antibodies, Monoclonal/PH; Drug Synergism; Interleukin-1/*PH; Interleukin-2/*BI/PH; Interleukin-6/*PH; Kinetics; Lymphocyte Transformation/*; Mice; Mice, Inbred BALB C; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; T4 Lymphocytes/*IM/ME. .T IL-6 and IL-1 synergize to stimulate IL-2 production and proliferation of peripheral T cells. .P JOURNAL ARTICLE. .W Purified T cells can be induced to proliferate and to produce the autocrine growth factor IL-2 with mAb to the TCR and costimulatory cytokines. In a previous report we demonstrated that human IL-6 stimulates IL-2 production and proliferation of purified T cells, in conjunction with the insolubilized anti-TCR V beta 8 mAb, F23.1. Here we show that when CD4+ T cells are rigorously purified to greater than 99% CD4+CD8-, they respond only weakly to F23.1 and IL-6. Instead, there is an additional requirement for IL-1, which dramatically synergizes with IL-6 to induce prolonged (greater than 7 days) proliferative responses and IL-2 production. Similar results were observed when the highly mitogenic anti-CD3 mAb 145-2C11 was substituted for F23.1. The proliferation induced by F23.1, IL-1, and IL-6 was substantially (greater than 80%) inhibited by a mAb to mouse IL-2, and was not inhibited by an anti-IL-4-mAb. In accordance with this finding, medium conditioned by the activated CD4+ cells contained large amounts of IL-2, which increased over a 7-day culture period. These results demonstrate that IL-6 and IL-1 stimulate T cell proliferation by inducing production of the autocrine growth factor IL-2. In addition, the two lymphokines must be present simultaneously for activation to occur. The possible roles of IL-6 and IL-1 in IL-2 gene regulation and in Ag-induced T cell activation are discussed. .A Holsti MA; Raulet DH. .I 201594 .U 90010119 .S J Immunol 9001; 143(8):2520-4 .M Animal; Cell Communication; Child; Human; Interleukin-1/*PH; Interleukin-2/BI/PH; Interleukin-6/*PH; Interphase; Leukocyte Count; Lymphocyte Transformation/*; Mice; Rats; Support, Non-U.S. Gov't; T-Lymphocytes/*IM/ME/PH. .T Distinct roles of IL-1 and IL-6 in human T cell activation. .P JOURNAL ARTICLE. .W We have examined the mechanisms underlying the activation of human T cells by IL-1 and IL-6. We report that PHA-stimulated accessory cell-depleted tonsillar T cells fractionated on the basis of their density show a high degree of heterogeneity in their proliferative response to these cytokines, inasmuch as small dense lymphocytes essentially fail to respond whereas large cells proliferate extensively. This differential response could be ascribed to the fact that only the large cells produced IL-2 under these circumstances, thus providing unequivocal evidence for the existence of an IL-2-mediated step in the activation of human T cells by IL-1 and IL-6. The synergy between IL-1 and IL-6 was found to result from their complementary effects on the production of and response to IL-2, with IL-1 playing a preponderant role in the induction of IL-2, and IL-6 being required, in addition to IL-1, for optimal IL-2-responsiveness. Using small tonsillar T cells, it was possible to show that, concomitant with the enhanced response to IL-2, IL-6 induced a marked increase in cell size and in protein synthesis. In the absence of other factors, this activation was not followed by entry into S phase, suggesting that the essential role of IL-6 in T cell activation is to induce the cells to move from G0 to G1, where they become more responsive to the small amounts of IL-2 induced by IL-1. .A Houssiau FA; Coulie PG; Van Snick J. .I 201595 .U 90010121 .S J Immunol 9001; 143(8):2530-3 .M Cell Line, Transformed; Cross-Linking Reagents; Human; Immunoblotting; Molecular Weight; Phosphorylation; Precipitin Tests; Protein-Tyrosine Kinase/*ME; Receptors, Antigen, T-Cell/*ME; Receptors, Interleukin-2/*ME; Tyrosine/IM. .T The beta-chain of the IL-2 receptor (p70) is tyrosine-phosphorylated on YT and HUT-102B2 cells. .P JOURNAL ARTICLE. .W IL-2 has previously been shown to rapidly induce activity of a tyrosine kinase. High-affinity IL-2 receptors that mediate the major mitogenic signals of IL-2 contain both p70 and p55 chains. p55 has no potential tyrosine phosphorylation sites and lacks consensus sequences found in protein tyrosine kinases. Inasmuch as the phosphorylation of hormone receptors is generally an important mechanism for regulating receptor function, we have now investigated the phosphorylation status of p70. By using anti-phosphotyrosine antibodies to immunoprecipitate affinity-labeled IL-2 receptors and to probe Western blots, we provide data suggesting that p70, but not p55, is constitutively tyrosine-phosphorylated on the leukemic cell lines studied. .A Sharon M; Gnarra JR; Leonard WJ. .I 201596 .U 90010123 .S J Immunol 9001; 143(8):2540-5 .M Animal; B-Lymphocytes/*IM/PH; Bone Marrow/*IM/PH; Cell Differentiation; Cell Survival; Cells, Cultured; Hematopoietic Stem Cells/IM/PH; Interleukin-4/PD/*PH; Lymphocyte Transformation/*/DE; Mice; Recombinant Proteins/PD; Signal Transduction; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.. .T The role of IL-4 in the generation of B lymphocytes in the bone marrow. .P JOURNAL ARTICLE. .W It has been indicated that IL-4 supports the maturation of pre-B cells to B lymphocytes. The present study was designed to investigate the mechanism by which IL-4 influences this maturational process. In order to determine whether IL-4 acts directly on pre-B cells, we sorted out B220+, sIg- cells from bone marrow of young adult (C3H X C57BL/6)F1 mice. These purified populations of pre-B cells (greater than 95%) were incubated with and without 4 to 200 U/ml of rIL-4, and the generation of new B lymphocytes in these cultures was followed for several days. We found that the frequency of newly generated B lymphocytes (%sIg+) was similar in control and in IL-4-containing cultures. However, the total number of B lymphocytes was significantly higher in IL-4-containing cultures. This high number of B lymphocytes was a result of an increased survival of cells in IL-4-containing cultures. The effect was IL-4 specific because anti-IL-4 antibodies completely prevented this phenomenon. We thus conclude that IL-4 does not induce the maturation of pre-B cells but may be important in the process of B lymphocytes generation by providing a signal for survival of these cells. .A Simons A; Zharhary D. .I 201597 .U 90010126 .S J Immunol 9001; 143(8):2560-6 .M Amino Acid Sequence; Animal; Antibodies, Monoclonal/AN/*IM; Antigen-Antibody Reactions; Antigenic Determinants/*AN/IM; Antigens, Differentiation, B-Lymphocyte/*AN/IM; Autoantibodies/*IM; Binding Sites, Antibody; Binding, Competitive; Connective Tissue Diseases/IM; Hela Cells; Human; Mice; Molecular Sequence Data; Peptide Mapping/*; Ribonucleoproteins/*AN/IM; Support, Non-U.S. Gov't. .T Mapping of B cell epitopes on small nuclear ribonucleoproteins that react with human autoantibodies as well as with experimentally-induced mouse monoclonal antibodies. .P JOURNAL ARTICLE. .W Small nuclear ribonucleoprotein (snRNP) particles are a class of RNA-containing particles in the nucleus of eukaryotic cells. They consist of uridylate-rich small nuclear RNA complexed with several proteins. snRNP particles U1, U2, U4/U6, and U5 all contain a common protein core consisting of proteins B'/B, D, D', E, F, and G. In addition to this core, U1 snRNP particles contain proteins 70K, A, and C, whereas U2 snRNP particles contain proteins A' and B". Almost any of the small nuclear RNA-associated polypeptides is targeted by autoantibodies in the sera from patients with SLE or related connective tissue diseases. We immunized a genetically non-autoimmune mouse with recombinant human B" protein and obtained three mAb reactive with native U2 snRNP particles. Two of these mAb particles cross-reacted with U1 snRNP, 9A9 and 11A1, via epitopes present on the U2 snRNP B" protein as well as on the U1 snRNP-specific A protein. A third mAb 4g3, reacted exclusively with U2 snRNP via a unique epitope on protein B". Two epitopes mapped at the carboxy-terminal region of the B" protein, whereas binding of the third mAb involved both amino- and carboxy-terminal amino acids of the B" protein. Epitope mapping, employing a DNAse I fragment library of the B" cDNA, revealed that the three mAb-reactive sites were discontinuous. Autoantibodies in sera from patients with SLE and other connective tissue diseases competed for binding with the mAb, implying that the mAb define a major autoantibody-reactive region on protein B". .A Habets WJ; Hoet MH; De Jong BA; Van der Kemp A; Van Venrooij WJ. .I 201598 .U 90010127 .S J Immunol 9001; 143(8):2567-74 .M Animal; Antigens, Differentiation/CL/*IP; Chromatography, Affinity; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Epithelium/ME; Horseradish Peroxidase/ME; Human; IgA/ME; IgG/CL/*ME; Intestinal Mucosa/*ME; Mice; Molecular Weight; Receptors, Fc/CL/*IP; Serum Albumin, Bovine/ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.. .T Identification of a unique IgG Fc binding site in human intestinal epithelium. .P JOURNAL ARTICLE. .W In experiments to determine whether serum antibodies in patients with Crohn's disease could be used as probes for detecting potentially etiologic Ag in the patients' tissues, we found that peroxidase (HRP)-labeled IgG from healthy persons, as well as from the patients, bound to normal colonic and small intestinal epithelium, mostly or entirely to goblet cells. The binding was due to a reaction involving the Fc region of IgG because HRP-labeled Fc fragments of IgG bound, but HRP-Fab, HRP-IgA, and HRP-bovine albumin did not, and because binding of HRP-IgG was inhibited competitively by unlabeled IgG or Fc fragments but not by IgG Fab fragments or IgA. These immunohistochemical results were confirmed by ELISA with microtiter wells coated with a sonicated homogenate from human colonocytes. The epithelial IgG Fc binding site was characterized by SDS-PAGE as consisting of a high Mr (greater than 200,000 Da) and a 78,000-Da component. It bound all four subclasses of human IgG and bound aggregated as well as monomeric IgG. It is distinct from known human Fc-gamma R by lack of recognition by mAb to those receptors and differences in affinity for various subclasses of human and murine IgG. This unique IgG Fc binding site might be involved in immunologic defense of the gut, perhaps by mediating reactions between foreign Ag and the contents of goblet cells. .A Kobayashi K; Blaser MJ; Brown WR. .I 201599 .U 90010128 .S J Immunol 9001; 143(8):2575-82 .M Animal; Antibodies, Monoclonal/PD; Antigens, Differentiation/IM/*IP; Binding, Competitive; Blotting, Northern; Cells, Cultured; Glomerular Mesangium/IM/*ME; IgG/IM/*ME; Immunoblotting; Immunoglobulins, Surface/ME; Iodine Radioisotopes/ME; Macromolecular Systems; Male; Precipitin Tests; Rats; Rats, Inbred Strains; Receptors, Fc/IM/*IP; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T A specific Fc gamma receptor on cultured rat mesangial cells. .P JOURNAL ARTICLE. .W Mesangial cells represent specialized pericytes in the renal glomerulus that contribute to the regulation of a variety of glomerular functions. Recently we and others have shown that cultured mesangial cells bind and take up immune complexes in an Fc-dependent manner leading in turn to generation of PGE2, reactive oxygen, and platelet-activating factor. The present studies were designed to further characterize potential Fc-gamma R on mesangial cells. Binding assays with either monomeric or heat aggregated (HA) [125I] labeled rat subclass-specific IgG were performed at 4 degrees C for 2 h on subcultured rat mesangial cells. Monomeric rat IgG2a, IgG2b, IgG1 and HA IgG2a bound only nonspecifically. Saturable Fc-dependent binding occurred for HA IgG2b and HA IgG1 though maximal binding and affinity were much higher for IgG2b. The presence of an Fc-gamma R was confirmed by surface protein iodination of mesangial cells (MC) and immunoprecipitation with either a polyclonal or mAb 2.4G2 prepared against murine Fc-gamma R. Both antibodies precipitated a 45-kDa iodinated protein band from cultured rat MC that comigrated with that from murine macrophage J774 cells on SDS-PAGE. This protein band also reacted with the polyclonal anti Fc-gamma R antibody on immunoblots. In contrast rat renal papillary epithelial cells were negative. The 45-kDa protein recognized by the rat anti-Fc-gamma R antibody 2.4G2 probably represents the binding site for HA IgG2b, as the 2.4G2 antibody also blocked binding of HA IgG2b. By immunofluorescence microscopy all MC stained positively with the polyclonal anti-Fc-gamma R antibody. A cDNA probe for the Fc-gamma RII-alpha on murine macrophages hybridized to mRNA from cultured rat MC which was of the same size (though less abundant) as that from J774 macrophages. These results further characterize the Fc-gamma R on cultured rat MC, and raise the possibility that the mesangial Fc-gamma R may play a role in the handling of immune-complexes by the renal glomerulus. .A Santiago A; Satriano J; DeCandido S; Holthofer H; Schreiber R; Unkeless J; Schlondorff D. .I 201600 .U 90010129 .S J Immunol 9001; 143(8):2583-8 .M Antibodies, Monoclonal/PD; Binding, Competitive; Chromatography, Affinity; Cross Reactions; Enterotoxins/IM/*ME; Human; HLA-DQ Antigens/GE/IM/*ME; HLA-DR Antigens/GE/IM/*ME; Kinetics; L Cells; Receptors, Endogenous Substances/*AN/IM; Staphylococcus aureus/*ME; Support, U.S. Gov't, P.H.S.; Transfection. .T Staphylococcal enterotoxin B and toxic shock syndrome toxin-1 bind to distinct sites on HLA-DR and HLA-DQ molecules. .P JOURNAL ARTICLE. .W Staphylococcal enterotoxins (SE) activate human T cells in vitro. This requires the presence of Ia+ accessory cells but does not require processing of the toxin by the accessory cell. We and others have recently demonstrated direct binding of SE to human MHC class II molecules. In this study, we have compared in detail the ability of class II molecules to bind two SE, toxic shock syndrome toxin-1 (TSST-1) and SEB. Scatchard analysis of equilibrium binding data indicate that SEB binds to Ia+ human cell lines with a 10-fold lower affinity than TSST-1. Likewise, SEB precipitates HLA-DR alpha- and beta-chains from detergent lysates of Ia+ cells less efficiently than TSST-1. The binding of TSST-1 and SEB to transfected L cells expressing HLA-DR and HLA-DQ gene products was differentially inhibited by anti-HLA-DR mAb. There was virtually no cross-inhibition of TSST-1 and SEB in competitive binding assays. We conclude that TSST-1 and SEB bind to two MHC class II sites which can be distinguished by their relative accessibility to blocking by anti-class II mAb and heterologous toxin. .A Scholl PR; Diez A; Geha RS. .I 201601 .U 90010133 .S J Immunol 9001; 143(8):2609-16 .M Adenosine Cyclic Monophosphate/*ME/PD; Alprostadil/BI/PD; Animal; Anti-Inflammatory Agents, Non-Steroidal/PD; Ascitic Fluid/MI; Blood Bactericidal Activity/*/DE; Burns/BL/*IM/MI; Cytoplasm/ME; Dinoprostone/PD; Female; Guinea Pigs; Male; Neutrophils/DE/IM/*ME; Superoxide/BL; Support, U.S. Gov't, Non-P.H.S.; Theophylline/PD. .T Bactericidal defect of neutrophils in a guinea pig model of thermal injury is related to elevation of intracellular cyclic-3',5'-adenosine monophosphate. .P JOURNAL ARTICLE. .W PG of the E series inhibit major effector functions of polymorphonuclear leukocytes (PMN) by elevating intracellular cAMP. The present study investigated the involvement of this mechanism in the bactericidal defect of PMN induced by thermal injury in a guinea pig model. Peripheral and peritoneal exudate PMN harvested from thermally injured guinea pigs at 1 or 2 days postburn had decreased bactericidal activity against Pseudomonas aeruginosa and a marked increase in cAMP content. Production of PGE1 by these cells in the absence of exogenous PMN activators was also increased. Treatment of PMN in vitro or in vivo with nonsteroidal anti-inflammatory drugs (indomethacin, ibuprofen, and piroxicam) restored bactericidal activity to normal and concomitantly reduced cAMP content and PGE1 production. A concomitant reduction in cAMP content and PGE1 production was also observed as bactericidal activity of PMN returned to normal under natural conditions during 4 to 7 days postburn. The enhancement of PMN bactericidal activity mediated by NSAID was fully counteracted by purified PGE1, theophylline, and by cAMP itself. These results suggest that the bactericidal defect of PMN induced by thermal injury is related to elevation of cAMP and that PGE1 plays a significant role in this phenomenon. .A Bjornson AB; Knippenberg RW; Bjornson HS. .I 201602 .U 90010135 .S J Immunol 9001; 143(8):2626-33 .M Animal; Antigens/*IM; Basophils/EN/IM/*ME; Calcium/*ME; Cell Line; Cell Membrane Permeability; Cell-Free System; Dinitrophenols/IM; Drug Synergism; Hydrogen-Ion Concentration; Hydrolysis; IgE/IM; Inositol Phosphates/ME; Leukemia/EN/IM/ME; Protein Kinase C/PH; Rats; Serum Albumin, Bovine/IM; Signal Transduction/*. .T The rise in concentration of free Ca2+ and of pH provides sequential, synergistic signals for secretion in antigen-stimulated rat basophilic leukemia (RBL-2H3) cells. .P JOURNAL ARTICLE. .W Ag stimulation of rat basophilic leukemia (RBL-2H3) cells results in hydrolysis of inositol phospholipids, a transient increase in concentration of cytosol Ca2+ [( Ca2+]i), a gradual increase in cytosolic pH (pHi) and the activation of protein kinase C. To determine whether all these changes serve as signals for secretion, studies were conducted with cells permeabilized with streptolysin O in which pHi and [Ca2+]i could be varied independently of each other and enzyme activities could be manipulated. At resting pHi (approximately 7.0) and [Ca2+]i (0.1 microM), the permeabilized cells showed little secretory response to Ag. At resting pHi, elevated levels of Ca2+ (0.33 microM) were required for maximal secretory response to Ag. At a pHi of 7.4, however, 0.1 microM [Ca2+]i was sufficient to sustain near maximal responses to Ag. Therefore, a small increase of [Ca2+]i to 0.33 microM was required to initiate secretion, but once the pHi was elevated secretion could be sustained at near basal levels of [Ca2+]i. Since elevating the [Ca2+]i and pHi, by themselves promoted little secretion, another potentiating signal must have been generated by antigen stimulation. This signal was possibly transduced via hydrolysis of inositol phospholipids and protein kinase C. Even with an elevated [Ca2+]i (0.33 microM) the hydrolysis of the phospholipids and secretion stimulated by Ag were inhibited by guanosine 5'(2-O-thio)diphosphate and neomycin. Furthermore, both protein-kinase C and the secretory response to Ag were lost after permeabilized cells were washed but both were retained if cells were exposed to PMA before permeabilization. .A Ali H; Collado-Escobar DM; Beaven MA. .I 201603 .U 90010136 .S J Immunol 9001; 143(8):2634-9 .M Amnion/ME; Antibodies, Monoclonal/PD; Binding, Competitive; Cell Movement/*/DE; Human; Monocytes/EN/*IM/ME; Plasminogen Inactivators/PD; Receptors, Endogenous Substances/*PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Urokinase/AI/IM/*PH. .T Endogenous receptor-bound urokinase mediates tissue invasion of human monocytes. .P JOURNAL ARTICLE. .W Macrophages have a marked capacity to invade tissue in the course of cellular immune reactions that is thought to be based on the action of urokinase (u-PA). u-PA is an ubiquitous serine protease that converts the zymogen plasminogen into the active protease plasmin. u-PA binds to specific receptors on the macrophage thereby enabling the cell to degrade interstitial tissue in the microenvironment. Two cytokines produced in the course of cellular immune reactions, IFN-gamma and TNF-alpha, increase the number of u-PA receptors on human cultured monocytes from 14,000 to 64,000 and 30,000 receptors/cell, respectively. We used an amnion invasion assay to investigate whether activated human monocytes exhibit an enhanced capacity to invade interstitial tissue in correlation to the increased numbers of u-PA receptors. We show in this study that IFN-gamma, which increases the number of endogenously occupied and saturable u-PA receptors, causes a threefold increase of monocyte invasion into amnion tissue in comparison to control cells. The anti-u-PA mAb MPW5UK, which blocks the activity of u-PA, inhibits monocyte invasiveness significantly. In contrast, TNF-alpha, which increases only the number of saturable u-PA receptors on monocytes, does not enhance their invasiveness. This finding suggests that only endogenously occupied u-PA receptors are instrumental in monocyte invasiveness. This conclusion is further supported by the findings that: 1) saturation of monocytes with u-PA does not further increase their invasiveness and that 2) plasminogen-activator inhibitor-2, a specific inhibitor of u-PA associated with endogenously occupied, but not of u-PA bound to saturable receptors, inhibits monocyte invasiveness completely. .A Kirchheimer JC; Remold HG. .I 201604 .U 90010138 .S J Immunol 9001; 143(8):2650-5 .M Adult; Antigenic Determinants/AN; Cell Movement/*; Clone Cells/IM; Cytotoxicity, Immunologic; Hepatitis B Surface Antigens/IM; Hepatitis B Virus/*IM; Hepatitis, Chronic Active/*IM; Human; HLA Antigens/GE/IM; Liver/*IM; Lymphocyte Transformation; Male; Support, Non-U.S. Gov't; T-Lymphocytes, Cytotoxic/*IM; Viral Envelope Proteins/*IM. .T Recognition of hepatitis B virus envelope proteins by liver-infiltrating T lymphocytes in chronic HBV infection. .P JOURNAL ARTICLE. .W The Ag specificity and cytotoxic function of human T cell clones, generated from lymphocytes infiltrating the liver of a chronic hepatitis B patient, were studied. Both class I- and class II-restricted T clones specifically proliferated to hepatitis B virus envelope proteins, but not to hepatitis B core Ag. The fine specificity of T cells was studied by using rAg having different composition in relation to HBV-envelope proteins or synthetic peptides of preS regions. The antigenic determinant recognized by T cell clones mapped to the preS2 region based on the response to r(preS1+preS2+S) and to r(preS2+S) and the failure to respond to S or preS1 alone. More precise epitope mapping was based on synthetic preS2 peptides 120-150 or 120-134, which stimulated both class I- and class II-restricted T clones, whereas preS2 153-171 or preS1 1-110 peptides did not; thus, the preS2 120-134 appears to contain both the residues binding to class I molecules and the residues binding to class II molecules. Moreover, strong and specific cytotoxic responses of these clones were observed only when HLA-matched EBV-lines, used as target cells, were previously sensitized with r(preS1+preS2+S) or preS2 peptides, which were shown to stimulate the clones. Thus, a preS2 epitope can represent a target Ag for liver-infiltrating T cells, which could kill the hepatocytes expressing the Ag plus the appropriate MHC molecule. .A Barnaba V; Franco A; Alberti A; Balsano C; Benvenuto R; Balsano F. .I 201605 .U 90010140 .S J Immunol 9001; 143(8):2663-9 .M Amino Acid Sequence; Animal; Antigen-Presenting Cells/IM; Antigenic Determinants/*IM; Antigenic Variation; Binding Sites, Antibody/*; Binding, Competitive; Hemagglutinins, Viral/GE/*IM; Histocompatibility Antigens Class II/*IM; Mice; Mice, Inbred BALB C; Orthomyxovirus Type A, Human/GE/*IM; Peptide Mapping; Peptides/*IM; Support, Non-U.S. Gov't; T-Lymphocytes/*IM; T4 Lymphocytes/IM/MI. .T I-Ad restricted T cell recognition of influenza hemagglutinin. Synthetic peptides identify multiple epitopes corresponding to antibody-binding regions of the HA1 subunit. .P JOURNAL ARTICLE. .W In a recent study, we reported extensive diversity in the Iak-restricted T cell repertoire for the hemagglutinin molecule (HA) of influenza A viruses (H3 subtype). Synthetic peptides identified six nonoverlapping epitopes on the HA1 subunit, and CD4+ T cell clones, specific for these regions, discriminated between natural variant viruses that had accumulated amino acid substitutions during antigenic drift. Here, we demonstrate similar specificity and diversity for the Iad haplotype and have identified multiple T cell epitopes within the sequences HA1 56-76, 71-91, 81-97, 177-199, 186-205, and 206-227. These also include recognition sites for neutralizing antibodies and correlations can be made between antigenic drift substitutions in H3 subtype viruses and the specificity of individual CD4+ clones for mutant HA. Moreover, these peptides appear not to exhibit structural homology and fail to compete for Ag presentation, indicating heterogeneity in peptide-Ia interaction. To explain the observation that CD4+ T cells, from two major haplotypes, recognize antibody binding regions of the HA molecule, we propose that surface Ig receptors of the Ag-specific B memory cell exert a direct effect on the processing of HA peptides and subsequent selection of the class II-restricted T cell memory repertoire after natural infection. .A Barnett BC; Burt DS; Graham CM; Warren AP; Skehel JJ; Thomas DB. .I 201606 .U 90010141 .S J Immunol 9001; 143(8):2670-6 .M Amino Acid Sequence; Animal; Antibodies, Monoclonal/*IM/TU; Antibodies, Protozoan/IM/TU; Antigen-Antibody Reactions; Antigenic Determinants/*IM; Antigens, Protozoan/GE/*IM; Antigens, Surface/GE/IM; Base Sequence; Chromosome Deletion; Cysteine/ME; Disulfides; Malaria/*IM; Male; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Molecular Weight; Plasmodium yoelii/GD/GE/*IM; Protein Precursors/*IM; Recombinant Proteins/IM; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T A protective monoclonal antibody recognizes an epitope in the carboxyl-terminal cysteine-rich domain in the precursor of the major merozoite surface antigen of the rodent malarial parasite, Plasmodium yoelii. .P JOURNAL ARTICLE. .W The 195-kDa major merozoite surface antigen of Plasmodium falciparum (Pf PMMSA) is a potential candidate for the development of a blood-stage malarial vaccine. We have focused on an analogous 230-kDa Ag of the rodent malarial parasite, Plasmodium yoelii, in an effort to study this protein in an experimental model system. Previously we reported the cloning and sequencing of a 2.1-kb portion of the gene encoding the carboxyl-terminal 77 kDa of the Py PMMSA. This region contained the B cell epitope recognized by mAb 302, a mAb shown to protect mice passively against P. yoelii challenge infection. To localize this B cell epitope, we have inserted various restriction fragments of the cloned Py PMMSA sequence into the bacterial expression vector pMG27NSTerm. Recombinant peptides of 74, 40, 34, 17, and 10 kDa have been produced which bear the epitope recognized by mAb 302. The results demonstrate that this B cell epitope is located within the most carboxyl-region of the Py PMMSA which contains a series of ten cysteine residues, also found in the PMMSA of P. falciparum. Further analysis showed that the reduction of disulfide bonds as well as the deletion of CYS-607 of the cloned sequence, resulted in the loss of the expression of this epitope. It is of interest that this epitope does not appear to be a dominant B cell determinant of the Py PMMSA molecule during infection. Inasmuch as this cysteine-rich domain of Py PMMSA displays considerable homology with that of Pf PMMSA, our data suggest that this region of the Pf PMMSA should be considered for inclusion in the development of a blood-stage vaccine. .A Burns JM Jr; Majarian WR; Young JF; Daly TM; Long CA. .I 201607 .U 90010143 .S J Immunol 9001; 143(8):2684-91 .M Acridine Orange; Animal; Antibodies, Protozoan/PH; Antigens, Protozoan/PH; Brain Diseases/*IM/MO; Chromium Radioisotopes/ME; Complement/PH; Cysts/*IM/MO; Cytotoxicity, Immunologic/*; Ethidium; Female; Human; Killer Cells, Lymphokine-Activated/*IM; Killer Cells, Natural/*IM; Lymphocyte Transformation; Mice; Stains and Staining; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Toxoplasma/GD/*IM/ME; Toxoplasmosis, Animal/IM/MO. .T Assessment of human natural killer and lymphokine-activated killer cell cytotoxicity against Toxoplasma gondii trophozoites and brain cysts. .P JOURNAL ARTICLE. .W Because previous work has suggested that NK cells may be important in host resistance against the intracellular parasite Toxoplasma gondii we examined whether human NK cells and lymphokine-activated killer (LAK) cells have activity against trophozoites and cysts of this organism in vitro. A method to radiolabel Toxoplasma trophozoites with 51Cr was developed and direct cytotoxic activity was determined by using modifications of the standard 51Cr release assay. Viability of 51Cr-labeled trophozoites assessed by both methylene blue staining and trypan blue exclusion was greater than 90%. Significantly more 51Cr was released by anti-Toxoplasma antibody and C than by antibody in the absence of C. Incubation of trophozoites with freshly isolated human NK cells or NK cells activated with either rIL-2 or rIFN-alpha did not result in significant release of 51Cr (specific lysis was 0 to 2.3%). In contrast, the average specific lysis of radiolabeled trophozoites by LAK cells was significant (specific lysis was 7.8% +/- 1.1, p less than 0.01). In a series of separate experiments, preincubation of radiolabeled trophozoites with heat-inactivated normal or Toxoplasma antibody-positive human serum increased the cytotoxicity of LAK cells from a mean specific lysis of 15% +/- 4.5 to 39% +/- 8.5, respectively (p less than 0.05), as assessed by 51Cr release. Because previous work has shown that radioisotope release from parasites may be nonspecific, separate experiments were performed to determine the cytotoxicity of LAK cells against antibody-coated trophozoites by using ethidium bromide-acridine orange staining to assess effector cell damage. LAK cells had a mean specific lysis of 51% against antibody-coated trophozoites by ethidium bromide-acridine orange staining. Preincubation with heat-inactivated Toxoplasma-antibody positive human serum did not increase activity of rIL-2-activated NK cells against 51CR-labeled trophozoites. Neither human NK cells (freshly isolated or activated by rIL-2 or rIFN-alpha) nor LAK cells were cytotoxic for purified preparations of cysts of Toxoplasma isolated from the brains of chronically infected mice. .A Dannemann BR; Morris VA; Araujo FG; Remington JS. .I 201608 .U 90010144 .S J Immunol 9001; 143(8):2692-8 .M Amino Acid Sequence; Antibodies, Monoclonal/IM; Antigenic Determinants/GE/*IP; Antigens, Viral/GE/IM/*IP; Avian Infectious Bronchitis Virus/GE/*IM; Binding Sites, Antibody; Coronaviridae/*IM; Molecular Sequence Data; Peptide Fragments/GE/IM; Peptide Mapping; Peptides/CS; Protein Conformation; Structure-Activity Relationship; Support, Non-U.S. Gov't; Viral Proteins/GE/*IP. .T Analysis of an immunodominant region of infectious bronchitis virus. .P JOURNAL ARTICLE. .W We analyzed the antigenic fine-structure of an immunodominant region in the peplomer protein of infectious bronchitis virus. This region near the N-terminus of the S2 subunit is recognized by polyclonal antisera and by the majority of mAb that cross-react with denatured protein. Despite their involvement in neutralization, epitopes in this region were conserved in different serotypes. Epitopes of four mAb and two chicken antisera were localized by using prokaryotic expression of cDNA fragments, and overlapping peptides with lengths increasing from 3 to 12 residues (PEPSCAN). We found overlapping epitopes with lengths of 6, 9, 11, and more than 17 residues. The results indicate that the expression products are antigenically equivalent to denatured protein fragments. This suggests a general strategy for the localization of sequential epitopes in large proteins. We propose that the immunodominance of the N-terminal region of S2 is explained by features of the protein structure. Presumably, this region is a protruding protein segment of about 20 residues with a high local mobility, as indicated by the antigenicity of the peptides. The conservation of the sequence points to an involvement in a molecular recognition process during infection. .A Kusters JG; Jager EJ; Lenstra JA; Koch G; Posthumus WP; Meloen RH; van der Zeijst BA. .I 201609 .U 90010145 .S J Immunol 9001; 143(8):2699-705 .M Amino Acid Sequence; Animal; Antigenic Determinants/AN; Antigens, Bacterial/AD/CS/*IM; Antigens, Surface/AD/*IM; B-Lymphocytes/AN; Carrier Proteins/IM; IgG/BI; Leukocytes, Mononuclear/ME; Macaca fascicularis; Macaca mulatta; Molecular Sequence Data; Molecular Weight; Peptides/AD/CS/*IM; Protein Conformation; Streptococcus mutans/*IM; T-Lymphocytes/AN; Thymidine/ME. .T Immunogenicity of synthetic peptides derived from the sequences of a Streptococcus mutans cell surface antigen in nonhuman primates. .P JOURNAL ARTICLE. .W The immunogenicity and antigenicity of synthetic peptides (SP) derived from the sequences of a cell surface Ag of Streptococcus mutans were investigated in macaque monkeys. Immunization with the free peptides of 11, 17, and 21 residues failed to elicit serum antibodies or T cell responses. However, immunization with the SP17 and SP21 linked to tetanus toxoid (TT) as a carrier elicited serum antibodies and proliferative responses of lymphocytes, not only to the SP but also to the native streptococcal Ag. In vivo recall of SP-TT immunized monkeys with suboptimal doses of the native streptococcal Ag resulted in a significant increase in antibodies, both to the SP and the streptococcal Ag, confirming that the SP shares antigenic epitopes with the native Ag. B and T cell epitopes were then determined and a B cell epitope was found in residues 8-13, whereas an overlapping T cell epitope was located in residues 7-15. The T cell epitope has an amino-terminal leucine and carboxy-terminal glycine and alanine added to residues 8-13 of the B cell epitope. In spite of the B and T cell epitopes being expressed in SP17 (residues 1-15), the monomer failed to induce serum antibodies without a carrier. However, immunization with a dimer of SP17 elicited both serum antibodies and proliferative responses of lymphocytes without a carrier. The results suggest that the monomeric SP17 is not immunogenic and needs to be dimerised in order to elicit antibodies and T cell responses, both to the SP and to the streptococcal Ag. .A Lehner T; Walker P; Bergmeier LA; Haron JA. .I 201610 .U 90010147 .S J Immunol 9001; 143(8):2714-22 .M Amino Acid Sequence; Antigens, Differentiation, B-Lymphocyte/GE/*IP; B-Lymphocytes/*AN/IM; Base Sequence; Blotting, Southern; Cell Line; Cloning, Molecular; Comparative Study; DNA/IP; Genes, Reiterated; Genes, Structural, Neoplasm; Hematopoietic Stem Cells/AN; Human; Lymphocyte Transformation/*; Molecular Sequence Data; RNA, Messenger/IP; Sequence Homology, Nucleic Acid; Support, U.S. Gov't, P.H.S.; Transfection; Tumor Cells, Cultured/*AN/IM. .T B7, a new member of the Ig superfamily with unique expression on activated and neoplastic B cells. .P JOURNAL ARTICLE. .W The human B cell restricted activation antigen B7 identifies an in vivo primed subpopulation of B cells that demonstrate an accelerated response to triggers of B cell activation and proliferation. The cDNA encoding B7 was molecularly cloned by cDNA expression. The identity of the B7 cDNA was confirmed by indirect immunofluorescence and immunoprecipitation of a 44/54-kDa protein from B7 transfected COS cells. The sequence of the B7 polypeptide predicts a type I membrane protein of 262 amino acids with eight potential N-linked glycosylation sites in the extracellular region and a short, highly positively charged cytoplasmic tail. The extracellular region is homologous to the Ig gene superfamily and consists of two contiguous Ig-like domains. The first Ig domain has the characteristics of a variable domain and the second that of a constant region domain. B7 mRNA was detected only on anti-Ig activated B lymphocytes and not in other hematopoietic cells. After in vitro activation of B cells with anti-Ig, B7 mRNA was maximally expressed between 4 and 12 h with four RNA transcripts of 1.7, 2.9, 4.2, and 10 kb. The 2.9-kb mRNA predominated in in vitro-activated B cells whereas the 1.7-kb mRNA was most abundant in tumor cells of B cell origin. B7 expression was confined to several histologically defined subgroups of B cell malignancies. The majority of non-Hodgkin's lymphomas were B7+ whereas the B cell leukemias and circulating non-Hodgkin's lymphomas were generally negative. These results demonstrate that the B7 gene encodes a unique molecule belonging to the Ig superfamily and that B7 expression is limited to normal activated B cells and noncirculating B cell malignancies. .A Freeman GJ; Freedman AS; Segil JM; Lee G; Whitman JF; Nadler LM. .I 201611 .U 90010151 .S J Immunol 9001; 143(8):2745-51 .M Antigenic Determinants/*IM; Chloramphenicol Acetyltransferase/ME; Human; HIV/*GE; Lymphocyte Transformation; Nucleic Acid Hybridization; Promoter Regions (Genetics)/*; Repetitive Sequences, Nucleic Acid; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; T-Lymphocytes/EN/IM/*MI; Transfection. .T HIV promoter activity in primary antigen-specific human T lymphocytes. .P JOURNAL ARTICLE. .W Human retroviruses, such as the HIV, infects human T cells, and efficient HIV replication occurs primarily in activated T cells rather than resting cells. Increased HIV production is likely caused by the activation of the retroviral promoter, and the HIV promoter may be regulated by intracellular signals induced during immune stimulation. To examine the regulation of retroviral promoter activity in normal, Ag-specific primary T lymphoblasts, a heterogeneous population of primary human T cells was transfected with either the HIV promoter or a promoter from a different retrovirus, Rous sarcoma virus (RSV) by protoplast fusion technique. Transfected T cells responded normally to Ag or mitogen stimulation, and activation of these T cells increased both the HIV and RSV promoter activity. Promoter activity was assessed by using transient expression assays after the T cells were restimulated with Ag, mitogen, or IL-2. In situ hybridization of transfected human T cells showed that 68 to 95% of activated lymphocytes expressed CAT mRNA directed by HIV or RSV. Thus, protoplast transfection of primary T cells was efficient in that the majority of cells expressed CAT message. By deletion of different regions of the HIV promoter, the enhancer region was identified as necessary for effective HIV promoter activity. In addition these deletion studies identified a region that negatively affects HIV promoter activity in primary T cells. Cotransfection of the HIV promoter with the HIV transactivator protein, tat, increases HIV promoter activity in both resting and activated primary human T cells only when the tat target sequences were present. .A Horvat RT; Wood C. .I 201612 .U 90010221 .S J Invest Dermatol 9001; 93(5):595-9 .M Absorption; Administration, Topical; Chromatography, Gas; Chromatography, High Pressure Liquid; Diffusion; Human; In Vitro; Isomerism; Isotretinoin/*ME; Light; Skin/*ME; Tretinoin/*ME/RE. .T Evidence for percutaneous absorption of isotretinoin from the photo-isomerization of topical tretinoin. .P JOURNAL ARTICLE. .W Tretinoin (0.1% Retin-A cream) was topically applied to human cadaver skin in vitro using Franz diffusion chambers. The photo-isomerization of tretinoin and retinoic acid percutaneous absorption in the absence of metabolic activity were assessed with and without ambient light exposure to the skin. Using HPLC, UV, and GC/MSD, a retinoid exhibiting identical chromatographic and spectral characteristics of isotretinoin was observed in the samples from the skin exposed to light, but was virtually absent in the skin samples maintained in the dark. From a single topical application of tretinoin, isotretinoin was as abundant as tretinoin in the chamber receiver solution, dermis, epidermis, and on the skin surface at 24 h after topical application. The data suggest the possibility that isotretinoin may have an important role in the pharmacology of topically applied tretinoin. .A Lehman PA; Malany AM. .I 201613 .U 90010223 .S J Invest Dermatol 9001; 93(5):610-5 .M Acute Disease; Alopecia/ET; Animal; Autoimmune Diseases/*CI/PA; Bone Marrow Transplantation/IM; Chronic Disease; Cyclosporins/*; Disease Models, Animal; Graft vs Host Disease/IM/PA; Rats; Rats, Inbred Strains; Scleroderma, Systemic/*IM/PA; Skin/PA; Support, Non-U.S. Gov't; X-Rays. .T Chronic cyclosporine-induced autoimmune disease in the rat: a new experimental model for scleroderma. .P JOURNAL ARTICLE. .W The pathogenesis of scleroderma is still elusive, although autoimmune mechanism involvement has been suggested. The present study was designed to investigate whether or not rat scleroderma would appear as one of the symptoms in a recently described model for autoimmune disease. The model is based on manipulation or reconstitution of the immune system after lethal irradiation and syngeneic bone marrow transplantation by temporary administration of the immunosuppressive drug cyclosporine-A. Withdrawal of cyclosporine-A 6-12 wk after bone marrow transplantation gives rise to autoimmune reactions causing clinical pathology similar to graft-versus-host disease. We discuss the chronic phase of this disease, approximately 30 wk after cyclosporine-A was withheld at that time-about one-third of the rats had developed histologic skin lesions comparable to those seen in patients with scleroderma. Therefore, we propose this model as a new, experimental autoimmune model for scleroderma in humans. .A Bos GM; Majoor GD; Willighagen RG; van Breda Vriesman PJ. .I 201614 .U 90010227 .S J Invest Dermatol 9001; 93(5):630-2 .M Animal; Bedbugs/*PY/RE; Gamma Rays; Insect Bites and Stings/*; Papilloma/*ET/PA; Rabbits; Skin Diseases/*ET/PA. .T Induction of skin papillomas in the rabbit, Oryctologus cuniculus, by bites of a blood-sucking insect, Cimex lectularius, irradiated by gamma rays. .P JOURNAL ARTICLE. .W Bed bugs, Cimex lectularius, irradiated with gamma rays were allowed to suck blood from shaved areas of the skin of rabbits, Oryctolagus cuniculus, 2 times/week for 5 months and then once weekly for another 5 months. This significantly induced the formation of skin papillomas and sweat gland hyperplasia in five out of nine experimental animals. It is speculated that the saliva of the irradiated bugs was activated by gamma rays and was responsible for the induction of skin papillomas. Because bed bugs play a significant role in the transmission of virus, it is also speculated that there is a virus in the saliva of bugs; this virus may be activated by gamma radiation and causes the development of papillomas in the skin. .A el-Mofty MM; Sakr SA; Younis MW. .I 201615 .U 90010228 .S J Invest Dermatol 9001; 93(5):633-40 .M Animal; Cell-Free System; Electron Spin Resonance; Epidermis/*ME; Free Radicals; Liposomes; Mice; Mice, Mutant Strains; Nitrogen Oxides; Oxidation-Reduction; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Thioredoxin Reductase (NADPH)/ME. .T Free radical reduction mechanisms in mouse epidermis skin homogenates [see comments] .P JOURNAL ARTICLE. .W Scavenging mechanisms for persistent free radicals were investigated using nitroxide-type radicals as model compounds. The free radical reducing activity of a) isolated thioredoxin reductase, a flavin containing oxidoreductase, b) skin homogenates, and c) the epidermis of hairless mice was studied by electron spin resonance spectroscopy. In all three systems, reduction rates of different classes of nitroxide free radicals exhibited the following order: oxazolidinoxy greater than piperidinoxy greater than dihydropyrroloxy. The main reductant for piperidinoxy radicals in mouse skin homogenate is ascorbic acid. Other reducing activities were stimulated by NAD(P)H and could be inhibited by N-ethyl maleimide, suggesting involvement of thiol-dependent processes. Mammalian thioredoxin, a competitive inhibitor of nitroxide reduction by thioredoxin reductase, significantly stimulates nitroxide scavenging in skin homogenate. Thioredoxin reductase did not significantly participate in nitroxide reduction in skin homogenates. At the surface of mouse epidermis a cationic dihydropyrroloxy nitroxide, which was stable in the presence of mammalian thioredoxin reductase was readily reduced. The epidermal reduction was inhibited by zinc, N-ethyl maleimide, and by heat (70 degrees C, 5 min). At least for mouse epidermis, reduction of a variety of nitroxides is a complex phenomenon involving enzymatic and nonenzymatic mechanisms and cannot be used as a specific assay for an enzyme, e.g., thioredoxin reductase. The study indicates the epidermis contains an effective antioxidant system that scavenges ascorbate-sensitive piperidinoxy nitroxides as well as more reducing radicals exemplified by dihydropyrroloxy nitroxides. .A Fuchs J; Mehlhorn RJ; Packer L. .I 201616 .U 90010230 .S J Invest Dermatol 9001; 93(5):649-55 .M Animal; Antigen-Presenting Cells/*IM; Antigens, Surface; Cell Line; Cells, Cultured; Dendritic Cells/IM; Epidermis/CY; Haptens; Helper Cells/*IM; Langerhans Cells/*IM; Lymphocyte Transformation/*; Major Histocompatibility Complex; Mice; Spleen/CY; Support, Non-U.S. Gov't. .T Characterization of primary T helper cell activation and T helper cell lines stimulated by hapten-modified, cultured Langerhans cells. .P JOURNAL ARTICLE. .W It has recently been shown that hapten-modified cultured Langerhans cells are able to activate small resting syngeneic L3T4+ T helper cells from nonsensitized animals. Repeated stimulation of these T cells with hapten-modified cultured Langerhans cells leads to the establishment of L3T4+ hapten-specific interleukin-4-producing T-cell lines. Here we report on further characteristics of primary hapten-dependent activation of L3T4+ T cells and of T-cell lines derived from them. Dendritic cell-enriched spleen cells were as able as Langerhans cells to activate nonsensitized T helper cells after hapten modification. However, M12c, a major histocompatibility complex class II-positive B-cell line that was able to activate small, resting, allogeneic L3T4+ T cells was not able to stimulate syngeneic T helper cells after hapten modification. Thy1+ dendritic epidermal cells did not significantly affect the magnitude of primary T helper cell proliferation induced by cultured Langerhans cells. Restimulation of in vitro primed T helper cells with hapten-modified cultured Langerhans cells revealed the presence, within the primed T helper cell population, of activated cells with specificity to an unrelated hapten, suggesting that, in hapten-dependent T helper cell activation, hapten-nonspecific cells are activated along with those that are hapten specific. Restimulation of a hapten-specific long-term T helper cell subline using different antigen-presenting cell types demonstrates that factors other than major histocompatibility complex class II density or tissue derivation of the antigen-presenting cell play a role in the activation of T cells in vitro. Finally, we demonstrate that in vitro generated hapten-specific T helper cell lines may not show strict major histocompatibility complex restriction. .A Hauser C; Yokoyama WM; Katz SI. .I 201617 .U 90010233 .S J Invest Dermatol 9001; 93(5):672-7 .M Cell Adhesion Molecules/*ME; Cell Movement; Endothelium, Vascular/ME; Epithelium/ME; Human; Hypersensitivity, Delayed/PA/*PP; Microscopy, Electron; Skin/IM/PA; Support, U.S. Gov't, P.H.S.; T-Lymphocytes/*IM; Time Factors; T4 Lymphocytes/IM. .T Intercellular adhesion molecule expression in the evolving human cutaneous delayed hypersensitivity reaction. .P JOURNAL ARTICLE. .W Intercellular adhesion molecule-1 (ICAM-1), putatively expressed by antigen-presenting or target skin cells, is a ligand for the lymphocyte function-associated antigen (LFA-1) present on circulating lymphocytes. Immunohistochemistry of normal adult human skin using monoclonal antiserum to ICAM-1 demonstrated focal reactivity restricted to endothelium lining the dermal microvasculature. Delayed hypersensitivity responses elicited with dinitrochlorobenzene in the skin of the same subject were evaluated sequentially over a 96 h period using immunohistochemical and ultrastructural techniques. The first alteration observed consisted of mast cell degranulation within perivenular foci in the superficial dermis at 4 h after antigen challenge. Sparse superficial perivascular T-cell infiltrates were present by 24 h. Progressive staining for ICAM-1 was observed in microvascular endothelium and in dermal dendritic cells between 24 and 48 h. ICAM-1 expression was documented focally within the lower epidermis at 48 h and diffusely within the lower and upper epidermal layers at 96 h. ICAM-1 expression by keratinocytes was consistently associated with T-cell migration into the epidermis, whereas migration was never observed in the absence of ICAM-1 reactivity. Immunoelectron microscopy confirmed ICAM-1 to be exclusively present on endothelial cells, dermal dendritic cells, mononuclear cells, and keratinocytes, and permitted characterization of the patterns of membrane reactivity. ICAM-1 expression by epidermal cells appears to be closely linked to the progressive migration of T cells from the dermis into the epidermis that characterizes cutaneous delayed hypersensitivity. .A Lewis RE; Buchsbaum M; Whitaker D; Murphy GF. .I 201618 .U 90010236 .S J Invest Dermatol 9001; 93(5):687-90 .M Cell Differentiation; Cell Survival; Cells, Cultured; Cytosine/AA/ME; DNA/*ME; Gene Expression Regulation; Human; In Vitro; Keratin/ME; Keratinocytes/*CY/ME; Methylation; Microscopy, Electron; Molecular Weight. .T DNA methylation and differentiation of human keratinocytes. .P JOURNAL ARTICLE. .W DNA methylation is a postreplicative modification thought to play a role in gene transcription in eucaryotes. Differences in the amount of 5-methylcytosine as a function of age and differentiation state have been reported. DNA isolated from human skin keratinocytes was analyzed for its 5-methylcytosine content. The 5-methylcytosine in DNA from neonatal and adult human keratinocytes was found to vary as a function of differentiation state. Differentiation of keratinocytes in vitro was promoted using a simple method where keratinocytes were plated directly onto the plastic surface of a culture flask, grown to confluence, and placed on a rocking culture platform that cyclically exposed the cells to air 50% of the time. Terminal differentiation was evident after approximately three weeks in culture. The 5-methylcytosine content of the DNA from differentiated human keratinocytes was 1.4%, whereas that of undifferentiated human keratinocytes was 3.1%. No difference in the 5-methylcytosine content of DNA as a function of the age of the donor was found. .A Veres DA; Wilkins L; Coble DW; Lyon SB. .I 201619 .U 90010237 .S J Invest Dermatol 9001; 93(5):691-4 .M Animal; Antigens, Differentiation, T-Lymphocyte/*AN; Antigens, Ly/IM; Clone Cells; Cytotoxicity, Immunologic; Graft vs Host Reaction; Histocompatibility Antigens Class II/IM; Immunization, Passive; Lymphocyte Transformation; Major Histocompatibility Complex; Mice; Skin Tests; T-Lymphocytes/*IM; T4 Lymphocytes/IM. .T T-cell clones with L3T4-positive or Lyt-2-positive phenotypes responding to mutant MHC class II antigen and inducing graft versus host reaction. .P JOURNAL ARTICLE. .W Two types of T cell clones responding to mutant major histocompatibility class II antigen (Iabm12) were established from spleen cells of C57BL/6 mice: one was L3T4-positive and the other Lyt-2-positive. These two types of clones carried functionally different properties. Lyt-2+ clones were absolutely dependent on exogenous interleukin-2 for their proliferation, whereas some L3T4+ clones secreted interleukin-2 and proliferated autonomously. Both types of clones had cytotoxic activities to bm12 target cells, and Lyt-2+ clones showed stronger activities than L3T4+ clones. Lyt-2+ clones induced induration in situ, whereas the L3T4+ clones induced ulcerative reaction when injected intradermally into mice. Histologically, the L3T4+ clones caused necrosis of the epidermis or upperdermis, while the Lyt-2+ clones induced infiltration of small round cells through the epidermis to the subcutaneous tissues and caused thickening of the epidermis. These characteristic reactivities might be due to a difference in lymphokines produced by each type of T cell subset in response to Iabm12 antigen. .A Watanabe H; Fujiwara M; Mashiko T; Ito M. .I 201620 .U 90010238 .S J Invest Dermatol 9001; 93(5):695-9 .M Adult; Benzalkonium Compounds; Croton Oil; Dermatitis, Contact/*PA; Epidermis/*DE/PA; Fatty Acids; Human; Male; Middle Age; Propanediols; Sodium Dodecyl Sulfate; Support, Non-U.S. Gov't. .T Epidermal damage induced by irritants in man: a light and electron microscopic study. .P JOURNAL ARTICLE. .W Irritant contact dermatitis may be induced by many chemicals and has a far greater incidence than allergic contact dermatitis. Despite this, it receives relatively little attention and its pathogenesis remains poorly understood. To gain a greater understanding of the interaction of irritants with the skin, we investigated the histopathological changes resulting from the topical application of a series of structurally unrelated irritants. Human volunteers were patch-tested with appropriate concentrations of nonanoic acid, sodium lauryl sulphate, dithranol, benzalkonium chloride, croton oil, and propylene glycol, which produced generally mild to moderate responses. Biopsy specimens were taken after 48 h and examined by light and electron microscopy. Spongiosis and the infiltration of predominantly mononuclear cells were observed in the epidermis of the majority of biopsy specimens, and were particularly pronounced and extensive in croton oil reactions. In addition, several irritants induced distinct and characteristic patterns of keratinocyte damage. Nonanoic acid and sodium lauryl sulphate caused morphologic changes indicative of disturbances in keratinocyte metabolism and differentiation, giving rise to dyskeratosis and parakeratosis respectively, while dithranol induced marked swelling of keratinocytes in the upper epidermis. The results suggest that there is a diversity and specificity in the histopathology of irritant contact dermatitis, reflecting the different ways in which chemicals may interact with components of the skin. .A Willis CM; Stephens CJ; Wilkinson JD. .I 201621 .U 90010239 .S J Invest Dermatol 9001; 93(5):700-2 .M Cells, Cultured; Cycloheximide/PD; Dactinomycin/PD; Diglycerides/*PD; Enzyme Activation/DE; Glycerides/*PD; Human; Isoquinolines/PD; Melanins/*BI; Piperazines/PD; Protein Kinase C/PH; Skin Pigmentation/DE; Sphingosine/PD; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Human melanogenesis is stimulated by diacylglycerol [see comments] .P JOURNAL ARTICLE. .W The intracellular signal pathways that mediate pigmentation in human skin are unknown. We now report that a diacylglycerol (DAG) analogue 1-oleoyl-2-acetyl-glycerol (OAG) 25-100 microns strikingly increased the melanin content of cultured human melanocytes in a dose dependent manner without altering growth rate. The pigment increase occurred within 24 h, was accompanied by increased incorporation of the melanin precursor L-3,4-dihydroxyphenyl alanine (DOPA), required new protein synthesis, and was completely blocked by the protein kinase C (PKC) inhibitors H-7 and sphingosine. A PKC-inactive DAG isomer had no effect on melanin per cell. These results implicate protein kinase C and its effector DAG in melanogenesis. .A Gordon PR; Gilchrest BA. .I 201622 .U 90010240 .S J Invest Dermatol 9001; 93(5):703-6 .M Antibodies, Monoclonal/*DU; Dose-Response Relationship, Radiation; DNA/RE; DNA Damage/*; DNA Repair/*; Enzyme-Linked Immunosorbent Assay; Human; In Vitro; Kinetics; Support, Non-U.S. Gov't; Ultraviolet Rays; Xeroderma Pigmentosum/GE/*PP. .T Repair of 254 nm ultraviolet-induced (6-4) photoproducts: monoclonal antibody recognition and differential defects in xeroderma pigmentosum complementation groups A, D, and variant. .P JOURNAL ARTICLE. .W Repair kinetics of ultraviolet (UV) light-induced (6-4) photoproducts in xeroderma pigmentosum complementation group A, D, and variant cells were studied by the enzyme-linked immunosorbent assay (ELISA) using a specific monoclonal antibody raised against (6-4) photoproducts, together with unscheduled DNA synthesis (UDS) and loss of T4 endonuclease V-susceptible sites (ESS). Group AXP35KO cells completely failed to repair both ESS (cyclobutane pyrimidine dimers) and antibody-recognizing (6-4) photoproducts until tested 24 h after irradiation, and had 2% early-time UDS. Group DXP43KO cells showed about 10% removal of both (6-4) photoproducts and ESS in 24 h, despite showing a residually higher level of 40% early-time and cumulative UDS. Thus, the results substantiated the extreme UV hypersensitivity of XP group A and D cells. However, XP52KO variant cells exhibited the normal level of UDS and ESS loss, but a slightly reduced repair of antibody-recognizing (6-4) photoproducts at 6 and 12 h after irradiation, which may account for a small UV hypersensitivity of the XP variant cells. .A Hiramoto T; Matsunaga T; Ichihashi M; Nikaido O; Fujiwara Y; Mishima Y. .I 201623 .U 90010242 .S J Invest Dermatol 9001; 93(5):708 .M Animal; Mast Cells/*PH; Mice; Mice, Mutant Strains/*PH; Psoriasis/*PP. .T Mast cells in asebia mouse skin [letter; comment] .P COMMENT; LETTER. .A Brown WR; Hardy MH. .I 201624 .U 90010245 .S J Invest Dermatol 9001; 93(5):709-10 .M Animal; Epidermis/IM; Human; Immunity, Cellular/*RE; In Vitro; Mice; Skin/IM/*RE; Suppressor Cells/IM; Ultraviolet Rays. .T UVB but not UVA exposure of human skin alters epidermal antigen presentation resulting in T-suppressor cell circuit activation [letter; comment] .P COMMENT; LETTER. .A Baadsgaard O. .I 201625 .U 90010246 .S J Infect Dis 9001; 160(4):567-71 .M Alanine Aminotransferase/BL; Animal; Blotting, Northern; Carrier State/*MI; Chimpansee troglodytes; Delta Agent/GE/IP/*PH; Delta Infection/ET/*MI; Hepatitis B/*CO/MI; Nucleic Acid Hybridization; RNA Probes; RNA, Viral/AN; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Virus Replication. .T Reappearance of hepatitis D virus (HDV) replication in chronic hepatitis B virus carrier chimpanzees rechallenged with HDV. .P JOURNAL ARTICLE. .W Four chronic hepatitis B virus (HBV) carrier chimpanzees, which had apparently cleared hepatitis D virus (HDV) after a first experimental challenge with HDV, were reinoculated with a homologous strain of HDV. All animals had reappearance of low levels of serum HDV RNA and transient, mild alanine aminotransferase (ALT) elevations, which in two cases correlated with HDV RNA positivity. Plasmas obtained from two chimpanzees after rechallenge were inoculated into two other chronic HBV carrier animals that had recovered from a previous HDV infection. A similar reappearance of HDV RNA in serum (without ALT elevation) was noticed. These same plasmas, however, when inoculated into a chronic HBV carrier chimpanzee never exposed to HDV caused a severe acute hepatitis D. Rechallenge with HDV in chimpanzees apparently recovered from a first HDV infection resulted in the reappearance of HDV replication, sometimes associated with hepatitis. This can be interpreted as reinfection with HDV, but other explanations are possible. Although the serum level of HDV RNA observed after rechallenge with HDV is low, its transmission to individuals susceptible to HDV infection can result in severe acute hepatitis D. .A Negro F; Shapiro M; Satterfield WC; Gerin JL; Purcell RH. .I 201626 .U 90010247 .S J Infect Dis 9001; 160(4):572-6 .M Animal; Cells, Cultured; DNA Replication; DNA, Viral/BI; Hepadnaviridae/GE/IM/*PH; Hepatitis Antibodies/AN; Hepatitis, Viral, Animal/*MI; Lipopolysaccharides/PD; Liver/EN; Lymphocyte Transformation/*; Lymphocytes/IM/*MI; Marmota/*MI; Sciuridae/*MI; Support, U.S. Gov't, P.H.S.; Virion/GE/PH; Virus Replication. .T In vitro production of infectious woodchuck hepatitis virus by lipopolysaccharide-stimulated peripheral blood lymphocytes. .P JOURNAL ARTICLE. .W Peripheral blood lymphocytes (PBLs) from a wild-caught woodchuck (WC192) chronically infected with woodchuck hepatitis virus (WHV) carried low levels of nonreplicating WHV genomes. In a previous study, these WHV genomes were induced to replicate and intact WHV particles were released when these PBLs were cultured in the presence of the generalized mitogen, lipopolysaccharide (LPS). To determine whether the culture-derived WHV particles were infectious, adult woodchucks were inoculated with cell-free culture medium from either LPS-stimulated or unstimulated WC192 PBLs. None of three animals inoculated with medium from the unstimulated PBL cultures developed positive WHV serologic markers or elevated liver enzyme levels during a 42-w observation period. In contrast, all three animals that received medium from the LPS-stimulated cultures displayed serologic markers of acute WHV infections 8-10 w after inoculation at up to a 100-fold dilution of the original culture medium. One of the three infected animals developed an acute hepatitis coincident with the appearance of the WHV markers. These results demonstrate that the WHV particles released from LPS-stimulated WC192 PBLs in culture are mature, infectious virions that also cause liver disease. Thus the LPS-induced replication of WHV in these cell cultures represents a transition from a latent to productive viral infection. .A Korba BE; Cote PJ; Shapiro M; Purcell RH; Gerin JL. .I 201627 .U 90010248 .S J Infect Dis 9001; 160(4):577-82 .M Adult; Alanine Aminotransferase/BL; Antigens, CD4/AN; Chronic Disease; Cross-Sectional Studies; DNA Replication; DNA, Viral/AN; Hepatitis B/*CO/MI; Hepatitis B e Antigens/AN; Hepatitis B Surface Antigens/AN; Hepatitis B Virus/GE/PH; Homosexuality; Human; HIV Antibodies/AN; HIV Infections/*CO; Male; Middle Age; Support, Non-U.S. Gov't; T4 Lymphocytes/IM; Virus Replication. .T The effect of concurrent human immunodeficiency virus infection on chronic hepatitis B: a study of 150 homosexual men. .P JOURNAL ARTICLE. .W To determine the influence of concurrent human immunodeficiency virus (HIV) infection on chronic hepatitis B virus (HBV) infection, 150 male homosexual chronic hepatitis B surface antigen (HBsAg) carriers were studied. Of these, 82 subjects (55%) tested positive for antibodies to HIV. They were more likely to express hepatitis B "e" antigen (HBeAg) (P less than .001) and HBV-DNA (P less than .0005) in serum than were HIV-seronegative individuals. However, the degree of immune suppression did not influence HBeAg-HBV-DNA expression. In HBeAg-seropositive subjects, concurrent HIV infection was associated with lower serum alanine transferase levels (P less than .001). This effect increased with the degree of immune suppression as determined by CD4+ lymphocyte counts. Conversely, in patients negative for HBeAg, there was a weak trend towards higher alanine transferase levels with concurrent HIV. This study suggests that chronic hepatitis B may be less severe when accompanied by HIV infection; however, greater viral replication may make it more contagious and resistant to antiviral therapy. These data support an immune-mediated pathogenesis for hepatitis B and have implications for its control. .A Bodsworth N; Donovan B; Nightingale BN. .I 201628 .U 90010250 .S J Infect Dis 9001; 160(4):589-98 .M Acyclovir/PD; Adolescence; Adult; Blotting, Southern; Burkitt's Lymphoma; Cell Line; Child; Child, Preschool; Deoxyribonuclease BamHI; DNA Probes; DNA Replication/*; DNA, Viral/AN; Epstein-Barr Virus/DE/GE/*PH; Female; Human; Immune Tolerance; Lymphoma/*MI; Lymphoproliferative Disorders/*MI; Male; Middle Age; Nucleic Acid Hybridization; Restriction Mapping; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured; Virus Replication/*. .T Latent and replicating forms of Epstein-Barr virus DNA in lymphomas and lymphoproliferative diseases. .P JOURNAL ARTICLE. .W Epstein-Barr virus (EBV) is associated with lymphomas and lymphoproliferative diseases that occur mainly in immunocompromised patients, but the role EBV plays in their pathogenesis is unclear. The evidence linking EBV etiologically to these disorders includes the presence of EBV DNA and nuclear antigens in the lesions and serologic evidence that some patients with these lesions are experiencing primary or reactivated EBV infections. These syndromes may represent proliferation of cells latently infected with EBV, but the possibility of viral replication has not been rigorously studied. DNA extracted from biopsies of 35 lymphoproliferative diseases was probed with regions of the EBV genome capable of distinguishing circular, episomal DNA found in latency from linear, replicating EBV DNA. All samples contained restriction fragments characteristic of fused termini, indicative of circular, latent genomes. Thirteen samples contained additional restriction fragments diagnostic of linear EBV DNA. Therefore, replicating EBV DNA is found in approximately 40% of EBV-associated lymphoproliferative disorders. .A Katz BZ; Raab-Traub N; Miller G. .I 201629 .U 90010251 .S J Infect Dis 9001; 160(4):599-603 .M Adolescence; Adult; Cervix Diseases/*EP/ET; Cohort Studies; DNA, Viral/AN; Female; Human; Interviews; Longitudinal Studies; Middle Age; Nucleic Acid Hybridization; Panama/EP; Papillomaviruses/GE/*IP; Prostitution/*; Recurrence; Risk Factors; Sex Behavior; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tumor Virus Infections/*EP/ET. .T Genital human papillomavirus infection in Panama City prostitutes. .P JOURNAL ARTICLE. .W Little is known of the natural history of genital human papillomavirus (HPV) infections in women from high-risk populations. Samples were collected from 183 Panama City prostitutes and assessed for HPV (filter in situ DNA hybridization) and for sexually transmitted agents. The cohort was followed for 8 mo; 51% of subjects completed four monthly return visits and 16% were sampled eight times. The proportion of women found infected with HPV increased significantly with increasing numbers of consecutive samples tested; 38 (21%) of 183 women were positive after one visit and 46 (82%) of 56 who completed six visits were infected. The pattern of viral detection over time was not random, which implied that most prostitutes were persistently infected with genital HPVs and that either scattered foci of infection or periodic reactivation of latent virus occurred. Our findings suggest that multiple sampling is necessary to accurately estimate HPV infection rates and to define whether patterns of DNA expression are present. .A Reeves WC; Arosemena JR; Garcia M; de Lao SL; Cuevas M; Quiroz E; Caussy D; Rawls WE. .I 201630 .U 90010252 .S J Infect Dis 9001; 160(4):604-10 .M Animal; Cell Line; Chimpansee troglodytes; Cold; Female; Hamsters; Immunosuppression; Influenza/*MI; Lung/MI; Mesocricetus; Orthomyxoviruses Type B/GE/*PH; Phenotype; RNA, Viral/AN; Turbinates/MI; Virus Replication/*. .T Attenuation and phenotypic stability of influenza B/Texas/1/84 cold-adapted reassortant virus: studies in hamsters and chimpanzees. .P JOURNAL ARTICLE. .W The temperature sensitivity, level of attenuation, and phenotypic stability of an influenza B/Texas/1/84 X B/Ann Arbor/1/66 cold-adapted (ca) reassortant virus that received the RNA segments that encode the hemagglutinin and neuraminidase surface glycoproteins from the B/Texas/84 wild-type virus and the remaining six RNA segments from the B/Ann Arbor/66 ca donor virus were evaluated. In comparison to wild-type virus, the ca reassortant was restricted in replication in the upper and lower respiratory tracts of hamsters and chimpanzees. This clearly demonstrated that the six transferable RNA segments of the B/Ann Arbor/66 ca donor virus specify the attenuation phenotype for animals with a 37 degrees C core body temperature. In addition, the ca virus retained the temperature-sensitive (ts) phenotype after replication in hamsters and chimpanzees. To further evaluate its phenotypic stability, the ca reassortant virus was isolated after 6-15 d of replication in hamsters that were immunosuppressed with cyclophosphamide, and the isolates were tested for their temperature sensitivity in vitro and for their level of replication in immunocompetent hamsters. The isolated viruses retained their ts and attenuation phenotypes even after prolonged replication in vivo. Thus, the B/Ann Arbor/66 ca donor virus can transfer the desired properties of attenuation and phenotype stability to its reassortants. The findings support the continued evaluation of ca reassortant influenza B virus vaccines in humans, including fully susceptible children. .A Snyder MH; London WT; Maassab HF; Murphy BR. .I 201631 .U 90010253 .S J Infect Dis 9001; 160(4):611-5 .M Acute Disease; Adult; Child; Disease Outbreaks/*; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Feces/MI; Food Contamination; Gastroenteritis/*EP/MI; Hemagglutination Tests; Human; Immunohistochemistry; Japan/EP; Microscopy, Electron; Middle Age; Rotavirus Infections/*EP/MI; Rotaviruses/GE/*IP/UL; RNA, Viral/AN. .T An outbreak of gastroenteritis associated with acute rotaviral infection in schoolchildren. .P JOURNAL ARTICLE. .W In April 1988 a large outbreak of group C rotavirus infection associated with acute gastroenteritis occurred among schoolchildren and their teachers simultaneously at seven elementary schools in Fukui city, Japan. Of 3,102, 675 (21.8%) became ill. Clinical symptoms were mild, predominantly abdominal pain and vomiting, with diarrhea reported in only 27.6%. The outbreak subsided within 2 d. No pathogenic bacteria were found in fecal specimens; the virus particles detected by electron microscopy were morphologically indistinguishable from conventional infantile rotavirus. Immune electron microscopy showed that these virions formed large aggregates with convalescent serum and with the reference serum specific to group C rotavirus. Polyacrylamide gel electrophoresis showed similar RNA patterns for virus from this outbreak and typical group C rotavirus. .A Matsumoto K; Hatano M; Kobayashi K; Hasegawa A; Yamazaki S; Nakata S; Chiba S; Kimura Y. .I 201632 .U 90010254 .S J Infect Dis 9001; 160(4):616-23 .M Antibiotics/*BL/PD; Bacteria/*DE; Blood/*; Blood Proteins/ME; Human; Kidney Failure, Chronic/BL; Protein Binding; Serum Bactericidal Test/*MT; Support, U.S. Gov't, Non-P.H.S.; Ultrafiltration. .T Use of serum ultrafiltrate in the serum dilution test. .P JOURNAL ARTICLE. .W Although pooled human serum diluent is advocated in the serum dilution test, its use may compensate for protein binding defects in patients and yield nonrepresentative titers. To test this hypothesis, comparison was made of serum ultrafiltrate (molecular weight cutoff less than or equal to 30,000) serially diluted into either pooled serum ultrafiltrate or Mueller-Hinton broth with patient serum samples diluted into pooled human serum in 111 assays from 55 patients and 6 volunteers. Of 111 bactericidal titers in ultrafiltrate and/or Mueller-Hinton broth, 101 were within a single twofold dilution of titers in pooled human serum. Nine of 10 discordant titers involved highly bound drugs and were usually higher in ultrafiltrate than in pooled human serum. In seven additional volunteers with renal failure, titers in ultrafiltrate and in each volunteer's serum were higher than those diluted in pooled human serum (P = .002). Recommended methods using pooled serum diluent may not accurately predict actual bactericidal titers in patients with abnormal protein binding. .A Leggett JE; Wolz SA; Craig WA. .I 201633 .U 90010258 .S J Infect Dis 9001; 160(4):644-50 .M DNA, Bacterial/AN; Electrophoresis, Agar Gel; Human; Plasmids/*; Skin/*MI; Staphylococcus/*GE/IP; Support, Non-U.S. Gov't. .T Exploration of the microbial anatomy of normal human skin by using plasmid profiles of coagulase-negative staphylococci: search for the reservoir of resident skin flora. .P JOURNAL ARTICLE. .W The aerobic bacterial flora of the top 25 layers of the stratum corneum of normal human skin was characterized by sampling glabrous skin with contact plates and analyzing plasmid patterns of coagulase-negative staphylococci (SCN) by agarose gel electrophoresis. The number of colonies of SCN on the skin surface at 12 sites varied from 14 to 838. Removal of five keratinized layers by sequential stripping with cellophane tape reduced the number of colonies by 80% (median; range, 42%-91%). Counts remained constant during removal of 20 additional layers. SCN with six different plasmid patterns were identified at a site on the skin surface. After removal of 25 layers, colonies with a single pattern were clustered in one quadrant of the site. The site was sterilized and covered with a sterile dressing for 18 h. Colonies reappeared in the same quadrant of the site; six of seven had the same pattern seen 18 h previously. Observations at three other sites were similar. Reappearance of the same strain(s) of SCN following sterilization of the site suggests that the reservoir for normal resident skin flora is located below the stratum corneum, perhaps in hair follicles and ducts of sebaceous glands. .A Brown E; Wenzel RP; Hendley JO. .I 201634 .U 90010263 .S J Infect Dis 9001; 160(4):678-85 .M Antigens, Fungal/*UR; Comparative Study; Enzyme-Linked Immunosorbent Assay; False Negative Reactions; False Positive Reactions; Histoplasma/*IM; Histoplasmosis/*DI; Human; Polysaccharides/*UR; Predictive Value of Tests; Radioimmunoassay; Regression Analysis; Support, U.S. Gov't, Non-P.H.S.. .T Comparison of sandwich solid-phase radioimmunoassay and two enzyme-linked immunosorbent assays for detection of Histoplasma capsulatum polysaccharide antigen. .P JOURNAL ARTICLE. .W Detection of a Histoplasma capsulatum polysaccharide antigen (HPA) has proved a useful approach to diagnosis of histoplasmosis. Two sandwich enzyme-linked immunosorbent assays (ELISAs) using alkaline phosphatase (AP)-or horseradish peroxidase (HRP)-conjugated antibodies were compared with solid-phase radioimmunoassay (RIA) for detection of HPA. The AP-ELISA and HRP-ELISA were each positive in 17 (89.5%) of 19 urine specimens from patients with disseminated histoplasmosis, while the RIA was positive in 18 (94.7%) of 19. Specimens from patients with nondisseminated histoplasmosis were positive by AP-ELISA in 8 of 32, by HRP-ELISA in 4 of 25, and by RIA in 12 of 25. Of control specimens from patients with other fungal infections, the AP-ELISA was negative in 22 (91.7%) of 24, the HRP-ELISA in 23 (95.8%) of 24, and the RIA in 23 (95.8%) of 24. Reproducibilities AP-ELISA and HRP-ELISA were 95.1% and 95.1%, respectively. Thus, AP-ELISA and HRP-ELISA appear less sensitive than RIA and may be falsely negative in specimens containing low levels of HPA. .A Zimmerman SE; Stringfield PC; Wheat LJ; French ML; Kohler RB. .I 201635 .U 90010265 .S J Infect Dis 9001; 160(4):692-9 .M Adult; Aged; Animal; Antibodies, Helminth/*BI; Antigens, Helminth/IM; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Human; IgE/BI; IgG/*BI; Immune Tolerance; Immunoblotting; Middle Age; Strongyloides/*IM; Strongyloidiasis/*IM; Support, U.S. Gov't, Non-P.H.S.. .T Prominence of IgG4 antibodies in the human responses to Strongyloides stercoralis infection. .P JOURNAL ARTICLE. .W The participation of the four subclasses of IgG in the humoral response to Strongyloides stercoralis was assessed by analyzing total and parasite-specific responses of each IgG subclass in 20 patients with uncomplicated strongyloidiasis and 21 immunocompromised patients with extraintestinal disease. The total component of each subclass was normal in most patients. IgG4 antibodies (measured by ELISA) were the most prominent parasite-specific response in both groups. Specific IgG2 and IgG4 responses were significantly more elevated in immunocompetent than in immunosuppressed patients. When the reactivity of each IgG subclass was analyzed by immunoblotting on SDS-PAGE-separated larval antigens, IgG4 recognized more antigens than did any other subclass. No parasite antigens were selectively recognized by either clinical group. Thus the continuous antigenic stimulation of chronic strongyloidiasis may result in an enhanced IgG4 subclass response. However, no presence or absence of humoral responses specific for filariform larval antigens was associated with the extraintestinal dissemination of the parasite. .A Genta RM; Lillibridge JP. .I 201636 .U 90010269 .S J Infect Dis 9001; 160(4):715-9 .M Animal; Cerebrospinal Fluid Proteins/AN; Complement 5a/AD/*CF/IM; Dinoprostone/AD/CF/*IM; Disease Models, Animal; Dose-Response Relationship, Drug; Leukocyte Count; Leukocytosis/CF; Male; Meningitis, Pneumococcal/*IM; Rabbits. .T Inhibition of complement-factor-5a-induced inflammatory reactions by prostaglandin E2 in experimental meningitis. .P JOURNAL ARTICLE. .W The possible role of complement factor 5a (C5a) and prostaglandin E2 (PGE2) in cerebrospinal fluid (CSF) pleocytosis and protein accumulation was assessed in a rabbit model of meningitis. Intracisternally administered C5a caused a rapid, early influx of leukocytes into CSF that peaked at 1 h after injection; by 6 h, cell counts were slightly higher than those in controls. Administration of PGE2 or saline did not induce detectable CSF leukocytosis. Coadministration of PGE2 with C5a decreased CSF leukocytosis in a dose-related fashion. Protein concentration increased 30 min after administration of C5a, peaked after 1 h, and remained elevated for 6 h. PGE2 caused a dose-related increase in protein content after 2 h, whereas coadministration caused an inversely dose-related inhibition of the C5a-induced protein influx into CSF. These data suggest that PGE2 in the subarachnoid space exerts an inhibitory action on the C5a-mediated response that is probably not related to its direct effects on protein extravasation. .A Kadurugamuwa JL; Hengstler B; Bray MA; Zak O. .I 201637 .U 90010270 .S J Infect Dis 9001; 160(4):720-2 .M Bandages/*AE; Catheterization, Central Venous/*; Cross Infection/*ET; Human; Prospective Studies; Septicemia/*ET. .T Clinically significant central venous catheter infections in a community hospital: association with type of dressing [letter; comment] .P COMMENT; LETTER. .A Dickerson N; Horton P; Smith S; Rose RC 3d. .I 201638 .U 90010271 .S J Infect Dis 9001; 160(4):722 .M Animal; California; Cattle; Jurisprudence/*; Legislation, Food/*; Milk/*MI. .T Certified raw milk in California [letter] .P LETTER. .A Fierer J. .I 201639 .U 90010272 .S J Infect Dis 9001; 160(4):722-4 .M Child; Epstein-Barr Virus; Fatigue Syndrome, Chronic/*; Human. .T A postviral chronic fatigue syndrome: a round table. .P JOURNAL ARTICLE. .A Levine PH; Krueger GR; Straus SE. .I 201640 .U 90010273 .S J Infect Dis 9001; 160(4):724-5 .M Acquired Immunodeficiency Syndrome/*DI; Biopterin/*AA/BL; Human; HIV-1/*PH; Virus Replication/*. .T Association between serum neopterin concentrations and in vitro replicative capacity of HIV-1 isolates [letter] .P LETTER. .A Fuchs D; Albert J; Asjo B; Fenyo EM; Reibnegger G; Wachter H. .I 201641 .U 90010274 .S J Infect Dis 9001; 160(4):725-6 .M Acquired Immunodeficiency Syndrome/*CO; Adult; Case Report; Cross Infection/*CO; Human; Male; Penicillin Resistance/*; Pneumococcal Infections/*CO; Streptococcus pneumoniae/*DE. .T Nosocomial infection with penicillin-resistant pneumococci in patients with AIDS [letter] .P LETTER. .A Blumberg HM; Rimland D. .I 201642 .U 90010275 .S J Infect Dis 9001; 160(4):727 .M Acquired Immunodeficiency Syndrome/*CO; Adult; BCG Vaccine/*AE; Case Report; Human; HIV-1; Lymphadenitis/*ET; Male. .T Bacille Calmette-Guerin adenitis 30 years after immunization in a patient with AIDS [letter] .P LETTER. .A Reynes J; Perez C; Lamaury I; Janbon F; Bertrand A. .I 201643 .U 90010276 .S J Infect Dis 9001; 160(4):727-8 .M Adult; Case Report; Ehrlichia; Human; Lyme Disease/*CO; Male; Rickettsiaceae Infections/*CO. .T Concurrent positive serology for ehrlichiosis and Lyme disease [letter] .P LETTER. .A Raad I; Singh V; Quan TJ. .I 201644 .U 90010278 .S J Infect Dis 9001; 160(4):730-2 .M Adult; Brain Abscess/*; Brucellosis/*; Case Report; Cerebellar Diseases/*; Human; Male. .T Brucella melitensis cerebellar abscess [letter] .P LETTER. .A Ayala-Gaytan JJ; Ortegon-Baqueiro H; de la Maza M. .I 201645 .U 90010279 .S J Infect Dis 9001; 160(4):732 .M Case Report; Human; Male; Middle Age; Septicemia/*; Vibrio cholerae/IP; Vibrio Infections/*. .T A case of non-O:1 Vibrio cholerae bacteremia from northern Europe [letter] .P LETTER. .A Wistrom J. .I 201646 .U 90010280 .S J Infect Dis 9001; 160(4):733 .M Bacteria, Aerobic; Bacterial Infections/*CO; Case Report; Child; Endophthalmitis/*ET; Human; Male; Pasteurella Infections/*CO. .T Endophthalmitis due to Pasteurella multocida and CDC EF-4 [letter] .P LETTER. .A Vartian CV; Septimus EJ. .I 201647 .U 90010282 .S J Infect Dis 9001; 160(4):735-6 .M Adult; Animal; Case Report; Chickens; Food Contamination; Food Microbiology/*; Human; Larva Migrans, Visceral/*ET; Male; Meat/*. .T Toxocariasis possibly caused by ingesting raw chicken [letter] [see comments] .P LETTER. .A Nagakura K; Tachibana H; Kaneda Y; Kato Y. .I 201648 .U 90010283 .S J Infect Dis 9001; 160(4):736-7 .M Animal; Antigenic Determinants/*AN; Antigens, Fungal/*IM; Cardiolipins/*IM; Human; Pneumocystis carinii/*IM. .T Evidence for shared epitopes between cardiolipin and Pneumocystis carinii [letter] .P LETTER. .A Masala C; Sorice M; Di Prima MA; Lenti L; Misasi R; Mojon M; Contini C; Vullo V. .I 201649 .U 90010582 .S J In Vitro Fert Embryo Transf 9001; 6(3):129-33 .M Female; Gamete Intrafallopian Transfer/*; Human; Infertility/*TH; Insemination, Artificial; Time Factors. .T Fallopian replacement of eggs with delayed intrauterine insemination (FREDI): an alternative to gamete intrafallopian transfer (GIFT). .P JOURNAL ARTICLE. .W This report contains details of what is the first group of patients with nontubal infertility to undergo fallopian replacement of eggs with delayed intrauterine insemination (FREDI). Twenty-three patients suffering from idiopathic or immune infertility, polycystic ovarian disease (PCOD), or mild endometriosis underwent follicular stimulation with human menopausal gonadotropin and/or pure follicle-stimulating hormone plus human chorionic gonadotropin prior to laparoscopic pickup of eggs of varying maturity. Eggs without spermatozoa were transferred at the time of laparoscopy. Subsequent high intrauterine insemination (IUI) of washed spermatozoa at a time when egg maturation within the tubes was judged to be complete enabled a cohort of fully capacitated spermatozoa to meet fully mature eggs in a totally physiological manner. Eight clinical pregnancies arose from this group, one healthy, male infant has been delivered, and four pregnancies remain ongoing. Although based on a small population of patients, it does seem that in vivo egg maturation following replacement in the fallopian tube is an effective alternative to in vitro maturation and, with the increased control over timing of egg insemination, leads us to propose FREDI as a flexible new therapeutic approach for the treatment of nontubal infertility. .A Leung CK; Leong MK; Chan YM; Wong CJ; Chan HH; Tucker MJ. .I 201650 .U 90010583 .S J In Vitro Fert Embryo Transf 9001; 6(3):134-7 .M Female; Fertilization in Vitro/*; Human; Mullerian Ducts; Pregnancy; Surrogate Mothers/*; Uterus/*AB. .T In vitro fertilization (IVF)-surrogacy: application of IVF to women without functional uteri. .P JOURNAL ARTICLE. .W Women with absent or dysfunctional uteri consented to controlled ovarian stimulation, ovum aspiration, in vitro fertilization, and embryo culture. Cleaving preembryos were transferred to recipient (surrogate) women whose menstrual cycles were in approximate synchrony with the ovum donor. None of the embryo recipients received medication. Six cases are described, resulting in one spontaneous loss at 6 weeks, four full-term deliveries, and one ongoing pregnancy. HLA typing demonstrated all babies to be genotypic offspring of the gamete donors. .A Sheean LA; Goldfarb JM; Kiwi R; Utian WH. .I 201651 .U 90010584 .S J In Vitro Fert Embryo Transf 9001; 6(3):139-41 .M Embryo Transfer/*; Endometrium/*PH; Female; Fertilization in Vitro/*; Human; Pregnancy; Time Factors. .T Double transfer of embryos in in vitro fertilization, or is there a delayed receptivity of the endometrium? .P JOURNAL ARTICLE. .W Sixty-seven in vitro fertilization (IVF) patients who underwent ultrasonically guided oocyte pickup (OPU) after induction of superovulation with human menopausal gonadotropins were submitted to two different protocols of embryo transfer. In the first group of 33 patients, four to five embryos were transferred to the uterus 48 hr after OPU. In the second group of 34 patients two to three embryos were transferred at 48 hr after OPU and two other embryos were transferred after freezing and thawing 48 hr later (96 hr after OPU). The pregnancy rate achieved in the double embryo transfer (ET) protocol was significantly higher than in the single-ET protocol (32.4 vs. 18.2%, respectively; P less than 0.05). .A Lewin A; Laufer N; Yanay N; Simon A; Zohav E; Berger M; Schenker JG. .I 201652 .U 90010587 .S J In Vitro Fert Embryo Transf 9001; 6(3):155-9 .M Bromocriptine/*PD; Estradiol/*ME; Female; Fertilization in Vitro/*; Human; Hyperprolactinemia/*ME; Oocytes/*DE; Pregnancy; Support, Non-U.S. Gov't; Time Factors. .T The influence of transient hyperprolactinemia on hormonal parameters, oocyte recovery, and fertilization rates in in vitro fertilization. .P JOURNAL ARTICLE. .W A detrimental effect of transient elevation of plasma prolactin (PRL) during in vitro fertilization (IVF) has not been proven; however, treatment with a dopamine agonist has been suggested. The present study was undertaken to determine if transient, midcycle hyperprolactinemia exerted a deleterious effect on the number of oocytes retrieved or on fertilization of oocytes in vitro. Fifty-three infertile patients with midcycle hyperprolactinemia (PRL greater than 20 micrograms/liter) during ovarian hyperstimulation for IVF were compared with 53 matched controls who remained normoprolactinemic. Mean (+/- SE) serum PRL levels on the day after hCG were significantly higher in the study group (29.5 +/- 1 micrograms/liter) than in the control (13.1 +/- 0.5 microgram/liter) (P less than 0.0005), whereas the mean estradiol (E2) concentrations on the same day were not significantly different (4822 +/- 287 and 4492 +/- 269 pmol/liters, respectively). Fertilization rates (72 +/- 4 and 70 +/- 4%, respectively) and the mean number of oocytes recovered (4.2 +/- 0.3 and 3.7 +/- 0.3, respectively) did not differ between the two groups. No correlation was observed between serum PRL and E2 levels, fertilization rates, or the number of oocytes retrieved in either group. Eleven patients with elevated PRL levels as a result of ovarian hyperstimulation were treated with 2.5 mg bromocriptine daily during the next IVF cycle. Serum PRL levels were significantly lower in the treated (5.6 +/- 1.8 micrograms/liter) than in the untreated cycles (35.6 +/- 3.1 micrograms/liter) (P less than 0.0005), whereas serum E2 concentrations did not differ.(ABSTRACT TRUNCATED AT 250 WORDS) .A Gonen Y; Casper RF. .I 201653 .U 90010588 .S J In Vitro Fert Embryo Transf 9001; 6(3):160-3 .M Adult; Case Report; Embryo Transfer; Estradiol/*ME; Female; Gamete Intrafallopian Transfer/*; Human; Oocytes/*ME; Pregnancy; Progesterone/*ME. .T Pregnancies established by gamete intrafallopian transfer and pronuclear-stage transfer in patients with premature ovarian failure using donated oocytes and low-dose oral micronized estradiol and progesterone. .P JOURNAL ARTICLE. .W This report describes both gamete intrafallopian transfer (GIFT) and pronuclear-stage transfer (PROST) of donated oocytes to patients with premature ovarian failure (POF), using micronized oral progesterone (P4) and low-dose micronized estradiol (E2) for endometrial preparation and maintenance. Patient A, with POF of 15 years' duration, received four donated oocytes for GIFT and subsequently delivered a normal, term, female infant. Patient B was diagnosed as POF 3 years ago. She received four donated oocytes, which were subsequently fertilized in vitro with husband's sperm. The following day, four pronuclear-stage embryos were transferred to her fallopian tubes. She recently delivered twin, healthy female infants. These procedures, along with exogenous hormonal development of the endometrium, provide a simplified means to establish and maintain pregnancy in POF patients. Both patients were maintained on low-dose micronized E2 prior to their procedure, Patient A on 3 mg E2 per day cyclically and Patient B on 0.5 mg E2 continuously. Micronized oral P4 was used to maintain pregnancy. .A Olar TT; Dickey RP; Curole DN; Taylor SN. .I 201654 .U 90010589 .S J In Vitro Fert Embryo Transf 9001; 6(3):164-7 .M Female; Fertilization in Vitro/*; Human; Pregnancy; Serum Albumin, Bovine/*PD; Support, Non-U.S. Gov't. .T Bovine serum albumin (BSA) can replace patient serum as a protein source in an in vitro fertilization (IVF) program. .P JOURNAL ARTICLE. .W Alternate protein sources have been suggested to replace the commonly used cord or patient serum for in vitro fertilization (IVF) procedures. During an 11-month period 127 patients treated for in vitro fertilization had either their serum (N = 71) or bovine serum albumin (BSA; N = 56) used as the protein source in the insemination and growth media. Ham's F-10 + 0.5% BSA was used for sperm swim-up and insemination media and 1% BSA was used for the growth media. Patient's serum was added to Ham's F-10 culture media at concentrations of 7.5 and 15% for insemination and growth, respectively. Embryo transfer was performed with Ham's F-10 containing 90% maternal serum in both groups. Fertilization rate of 259 oocytes inseminated in medium containing patient's serum did not differ when compared with 200 oocytes inseminated in medium containing BSA. Likewise, rates of abnormal fertilization, cleavage, and pregnancy were similar in both groups. In a second experiment, 148 normally fertilized oocytes were transferred after 24 hr in culture to growth media containing two different concentrations of BSA (0.5 or 1%). Cleavage rates for the two groups were similar and the percentage of embryos developed to greater than or equal to 4 cells did not differ significantly. We conclude that a single concentration of BSA can safely be used to supplement culture media in human IVF with several practical and economical benefits. .A Benadiva CA; Kuczynski-Brown B; Maguire TG; Mastoianni L Jr; Flickinger GL. .I 201655 .U 90010591 .S J In Vitro Fert Embryo Transf 9001; 6(3):176-9 .M Animal; Embryo/*; Female; Freezing/*; Mice; Organ Culture/*MT; Preservation, Biological/*; Support, Non-U.S. Gov't. .T The effect of prefreeze in vitro culturing on the success of embryo freezing in mice. .P JOURNAL ARTICLE. .W There is currently a controversy as to whether the prolonged in vitro culturing of embryos before freezing has a deleterious effect on their ability to survive freezing and thawing. We compared the survival rate of frozen/thawed mouse embryos after in vitro culturing, from the two-cell stage through the eight-cell, morula, and blastocyst stages, with the survival of embryos developed in vivo to the same stages. Following induced superovulation and mating, embryos in the desired cleavage stage were flushed from the oviducts and/or uterus and either cultured in vitro or frozen immediately in sterile glass ampoules to -40 degrees C and plunged into liquid nitrogen for storage. Dimethyl sulfoxide (1.5 M) was used as cryoprotectant. After thawing, the survival rate (determined by the morphological appearance of the embryos) was significantly lower in the eight-cell stage embryos in the group grown in vivo (P less than 0.05). The number of embryos developing into expanded and hatched blastocysts was not significantly different when the in vivo vs in vitro cultures were compared over each of the three cleavage stages: eight cells (82 vs 83%), morula (92 vs 87%), and blastocyst (33 vs 51%), respectively. There was a significant decrease in the development rate of blastocyst-stage embryos when compared with earlier stages under both culture conditions (P less than 0.001). It is concluded that, compared to in vivo-grown embryos frozen at the same stages, prolonged in vitro culture does not reduce the embryos' ability to develop normally. .A Pellicer A; Lightman A; DeCherney AH. .I 201656 .U 90010593 .S J In Vitro Fert Embryo Transf 9001; 6(3):185-7 .M Adult; Case Report; Female; Fertilization in Vitro/*; Human; Oocytes/*; Ureter/*IN; Ureteral Obstruction/*ET. .T Traumatic ureteric obstruction secondary to oocyte recovery for in vitro fertilization: a case report. .P JOURNAL ARTICLE. .A Jones WR; Haines CJ; Matthews CD; Kirby CA. .I 201657 .U 90010594 .S J In Vitro Fert Embryo Transf 9001; 6(3):188 .M Female; Human; Surrogate Mothers/*; Triplets. .T Surrogate gestational carriers [letter] .P LETTER. .A Utian WH. .I 201658 .U 90010618 .S J Lab Clin Med 9001; 114(4):378-81 .M Animal; Bone Marrow/CY; Cell Differentiation; Cell Line; Comparative Study; Female; Granulocytes/*CY; Hematopoiesis/*; Hematopoietic Stem Cells/*CY; Megakaryocytes/*CY; Mice; Mice, Inbred C57BL; Spleen/CY; Support, Non-U.S. Gov't. .T Role of the microenvironment on hematopoiesis. I. Stem cell differentiation into granulocytic and megakaryocytic cell lineage. .P JOURNAL ARTICLE. .W Lineage commitment and differentiation of stem cells derived from bone marrow was investigated by using specific histochemistry for identification of spleen colonies. The number of colonies formed by injection of 1 x 10(5) bone marrow cells into irradiated murine syngeneic recipients was similar to the previously reported results with 1 x 10(6) spleen cells. The results of this study with bone marrow-derived cells have been compared with those from studies done with spleen-derived cells. A significant increase (p less than 0.01) was observed in the number of granulocytic colonies formed by bone marrow cells versus spleen-derived cells. This suggests that bone marrow-derived cells promote granulopoiesis in the recipient spleen. A 50% increase of megakaryocyte colonies was observed within the splenic pulp in the midzone region when compared with that on the surface (p less than 0.01). This indicates that the splenic microenvironment in this area was conducive for megakaryocytopoiesis. These results provide further evidence of the influence of the microenvironment on hematopoiesis. .A Choudhury C. .I 201659 .U 90010619 .S J Lab Clin Med 9001; 114(4):382-8 .M Animal; Cell Cycle; Cell Differentiation; Cell Survival; Cells, Cultured; Colony-Forming Units Assay; Granulocytes/*CY/ME; Hamsters; Hematopoiesis/*; Megakaryocytes/*CY/ME/UL; Mesocricetus; Stem Cells/CY; Support, Non-U.S. Gov't; Thymidine/ME. .T Role of the microenvironment on hematopoiesis. II. Regulation of cell kinetics in vitro during granulopoiesis and megakaryocytopoiesis. .P JOURNAL ARTICLE. .W A long-term liquid culture system derived from adult Syrian hamster spleen that supports hematopoiesis from a single inoculum without supplemental coritcosteroids was used. Clonal assays from progenitor cells in the supernatant and adherent phases of liquid cultures revealed an increased concentration of myeloid and megakaryocytic progenitor cells in the adherent layer. Cell kinetic studies with these stable unstimulated cultures indicate that the initially labelling cohort of cells were present in the adherent cell layer. However, incorporation of tritiated thymidine into DNA occurred in less than 5% of the total cells present in the adherent cell layer. The data indicate that regulation of hematopoiesis by the stromal microenvironment was achieved by maintaining hematopoietic cells in a quiescent G0 or prolonged G1 phase and was associated with the initially labeling cells. The assays demonstrate the phenomenon that megakaryocyte precursors were present almost exclusively on the adherent stromal cell layer, which also contained a storage pool of mature megakaryocytes. The mature cells did not undergo further DNA synthesis and did not show morphologic changes of senescence. Cell kinetic studies revealed that megakaryocytes were released into the supernatant phase from the adherent stromal layer after endomitosis had occurred and cytoplasmic maturation ensued, indicating a role of stromal cells in megakaryocyte differentiation, maintenance, and maturation. The results of these investigations provide additional data on the regulation of megakaryocytopoiesis by the microenvironment. .A Choudhury C; Sparks R. .I 201660 .U 90010620 .S J Lab Clin Med 9001; 114(4):389-93 .M Animal; Complement/*PH; Eicosanoids/*BI; Glomerular Filtration Rate; Hemodynamics; Immune Sera/IM; Kidney Glomerulus/*ME; Male; Nephritis/IM/*ME/PP; Rats; Rats, Inbred Strains; Renal Circulation/*; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Effects of complement depletion on glomerular eicosanoid production and renal hemodynamics in rat nephrotoxic serum nephritis. .P JOURNAL ARTICLE. .W The role of complement in mediating the changes in renal hemodynamics and glomerular eicosanoid synthesis after the administration of heterologous antibody against rat glomerular basement membrane (AGBM) was studied in Munich-Wistar rats. AGBM serum decreased glomerular filtration rate (GFR) and increased glomerular thomboxane B2 (TxB2) production without associated changes in glomerular prostaglandin E2 (PGE2) or PGF2 alpha production. Pretreatment of rats with cobra venom factor to deplete complement blocked the fall in GFR produced by AGBM without altering the increment in glomerular TxB2 production. In these animals, glomerular PGE2 synthesis was elevated. The results indicate that the salutary effects of complement depletion in nephrotoxic serum nephritis are not mediated by changes in the glomerular production of the vasoconstrictor TxA2. An enhanced production of PGE2 may participate in preventing the fall in GFR after AGBM administration in the complement-depleted rats. .A Garcia-Estan J; Roman RJ; Lianos EA; Garancis J. .I 201661 .U 90010621 .S J Lab Clin Med 9001; 114(4):394-400 .M Cell Line; Electrophoresis, Polyacrylamide Gel; Human; Immunochemistry; Peptide Mapping; Precipitin Tests; Receptors, Antigen, T-Cell/*; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Components of the human T lymphocyte antigen receptor complex, CD3-p28 and CD3-gamma, are biochemically distinct. .P JOURNAL ARTICLE. .W A recently described subunit of the T cell antigen receptor-CD3 complex, p28, is very similar to the mature CD3-gamma subunit with respect to electrophoretic mobility. We demonstrated, by one- and two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and endo-beta-n-acetylglucosaminidase digestion, that CD3-p28 and CD3-gamma coexist in CD3-specific immunoprecipitates from the human T lymphocyte hybrid cell line 255.88, which was labeled by biosynthetic incorporation of radioactive amino acids. By partial proteolysis and peptide mapping, we demonstrated that CD3-p28 and CD3-gamma are distinct members of the CD3 complex. .A Stewart SJ; Levy R. .I 201662 .U 90010622 .S J Lab Clin Med 9001; 114(4):401-6 .M Erythrocyte Deformability/DE; Erythrocyte Membrane/ME; Erythrocytes/*ME; Fatty Acids/BL; Glutathione/BL; Human; Methemoglobin/AN; Osmolar Concentration; Oxidation-Reduction/DE; Sesquiterpenes/*PD; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Qinghaosu-mediated oxidation in normal and abnormal erythrocytes. .P JOURNAL ARTICLE. .W Qinghaosu, a potent antimalarial agent, has recently been shown to act via oxidative mechanisms. Hence, we have investigated what effect qinghaosu has on cellular oxidation in normal and oxidant-sensitive red blood cells (RBCs). At 500 mumol/L, qinghaosu was found to directly alter red cell deformability (DI) in both normal (hemoglobin AA) and abnormal (hemoglobins SS, AE, and EE) RBCs, with the maximum DI being 70% to 80% of that of untreated RBCs. Although concentrations of less than or equal to 200 mumol/L qinghaosu had a minimal effect on the maximum DI, qinghaosu was found to act as an efficient prooxidant at these concentrations. Cellular deformability was lost more rapidly in response to exogenous oxidants in the qinghaosu-treated RBCs than in control cells. Hemoglobin SS and EE RBCs pretreated with qinghaosu demonstrated a much more rapid decrease in cellular deformability than did the control RBCs in response to exogenous oxidants. Additionally, qinghaosu resulted in a dose-dependent increase in red cell lysis and methemoglobin generation while decreasing reduced glutathione concentration. As a consequence of qinghaosu challenge, a decrease in unsaturated fatty acids was noted. Deoxyqinghaosu, which lacks the endoperoxide bridge and is pharmacologically inactive, did not affect cellular deformability and did not function as a prooxidant. Additionally, deoxyqinghaosu had no effect on fatty acid composition, red cell lysis, methemoglobin generation, or reduced glutathione concentration. In conclusion, although the oxidative effects of qinghaosu on uninfected erythrocytes were only seen at concentrations much greater than that necessary for antimalarial activity, these results confirm the proposition that qinghaosu may act via oxidative mechanisms. Furthermore, qinghaosu-mediated oxidation was significantly increased in erythrocytes characterized by enhanced oxidant sensitivity caused by unstable hemoglobins. .A Scott MD; Meshnick SR; Williams RA; Chiu DT; Pan HC; Lubin BH; Kuypers FA. .I 201663 .U 90010623 .S J Lab Clin Med 9001; 114(4):407-10 .M Adult; Aged; Carrier State; Enzyme-Linked Immunosorbent Assay; Female; Human; HTLV-I Infections/*CO; Leukemia-Lymphoma, T-Cell, Acute, HTLV-I-Associated/BL; Leukemia, T-Cell, Chronic/BL; Male; Middle Age; Paraparesis, Tropical Spastic/BL; Receptors, Interleukin-2/*ME; Spinal Cord Diseases/BL/*ET. .T Elevated serum levels of soluble interleukin-2 receptors in HTLV-I--associated myelopathy. .P JOURNAL ARTICLE. .W Using an enzyme-linked immunosorbent assay, we measured the level of soluble interleukin-2 receptors (sIL-2Rs) in the serum of 50 normal controls, 48 human carriers of T cell leukemia virus type I (HTLV-I) antibody who had no symptoms, 11 patients with HTLV-I-associated myelopathy (HAM), and 39 patients with adult T cell leukemia (ATL) (four smoldering, 10 chronic, nine lymphoma, and 16 acute type). The highest levels of sIL-2R were observed in patients with acute and lymphoma-type ATL, as opposed to those with chronic and smoldering-type ATL. The levels of sIL-2R in patients with HAM were roughly between those of smoldering ATL and healthy HTLV-I carriers. Serum sIL-2R levels in healthy carriers were also elevated compared with those in normal controls. These observations suggest that the measurement of sIL-2R levels in patients with ATL can be useful as a noninvasive measure of tumor burden and should aid in the understanding of the natural history of HTLV-I infection leading to the development of ATL. .A Yamaguchi K; Nishimura Y; Kiyokawa T; Takatsuki K. .I 201664 .U 90010624 .S J Lab Clin Med 9001; 114(4):411-8 .M Amino Acid Chloromethyl Ketones/*PD; Animal; Antithrombins/CS/*PD; Blood Cell Count/DE; Blood Coagulation/*DE; Blood Platelets/DE; Complement/AN; Drug Resistance; Equipment Failure; Hemodialysis/*/IS; Heparin/*PD; Male; Papio; Support, U.S. Gov't, P.H.S.. .T Prevention of heparin-resistant thrombotic occlusion of hollow-fiber hemodialyzers by synthetic antithrombin. .P JOURNAL ARTICLE. .W Because heparin anticoagulation during hemodialysis with hollow-fiber devices is associated with progressive loss of volume of fiber bundles subsequent to thrombotic occlusion, we examined the antithrombotic and antihemostatic effects of the irreversible synthetic thrombin inhibitor D-phenylalanyl-L-prolyl-L-arginyl-chloromethylketone (FPRCH2Cl) during repeated exposure of cupramonium cellulose hollow-fiber hemodialyzers in an extracorporeal blood circuit in baboons. By contrast with full anticoagulating doses of heparin, FPRCH2Cl (100 nmol/kg/min) decreased both the loss of fiber bundle volume (19.1% +/- 7.0% vs 6.4% +/- 3.6% p less than 0.01) and deposition of 111In-labeled platelets within the dialyzer (15.7 +/- 5.9 x 10(9) vs 3.2 +/- 1.2 x 10(9) platelets; p less than 0.01). Additionally, blood markers of thrombus formation in vivo (i.e., plasma beta-thromboglobulin, platelet factor 4, and fibrinopeptide A) remained at low levels throughout infusion of FPRCH2Cl, whereas levels were elevated during heparin therapy (p less than 0.01 in each case). FPRCH2Cl, but not heparin, prolonged bleeding times (p less than 0.001) without affecting the capacity of platelets to aggregate in response to the presence of either collagen or adenosine diphosphate ex vivo. Complement activation by the dialyzer was not affected by FPRCH2Cl. We conclude that the progressive loss of dialyzer hollow fibers is a platelet-dependent, thrombin-mediated process that, although resistant to heparin, is interrupted by the synthetic antithrombin FPRCH2Cl. .A Kelly AB; Hanson SR; Henderson LW; Harker LA. .I 201665 .U 90010625 .S J Lab Clin Med 9001; 114(4):419-25 .M Animal; Bronchoalveolar Lavage Fluid/CY/EN; Cathepsin B/*ME; Macrophages/*EN; Male; Pulmonary Alveoli/CY/*EN; Rats; Rats, Inbred Strains; Smoke/*; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Tobacco/*. .T Cigarette smoke stimulates cathepsin B activity in alveolar macrophages of rats. .P JOURNAL ARTICLE. .W Cathepsin B activity was determined in alveolar macrophages and cell-free bronchoalveolar lavage fluid from Sprague-Dawley rats exposed only through the nose to fresh mainstream smoke from University of Kentucky high-tar, high-nicotine reference cigarettes, and in cells and fluid from room control and sham control animals. Increased levels of blood carboxyhemoglobin and pulmonary aryl hydrocarbon hydroxylase activity in smoke-exposed animals indicated effective exposure of animals to cigarette smoke. Cathepsin B activity was quantitated with alpha-N-benzyloxycarbonyl-leucine-leucine-arginine-2-naphthylamide as substrate. Specific activity (nanomoles of substrate cleaved per milligram of protein per hour) in alveolar macrophages was increased by 43% at both 4- and 10-week exposure points in animals exposed twice daily to 10 puffs of cigarette smoke. These data indicate that maximal stimulation of the enzyme occurs within 4 weeks of the initiation of smoke exposure. When the activity was expressed on a per-cell basis, cathepsin B activity was also increased in the smoke-exposed group at both exposure points. Activity in bronchoalveolar lavage fluid of smoke-exposed animals was increased by approximately 50% at 4 and 10 weeks, but the differences were not statistically significant. These findings demonstrate that cigarette smoke is a potent inducer of cathepsin B activity in alveolar macrophages of rats. .A Gairola CG; Galicki NI; Cardozo C; Lai YL; Lesser M. .I 201666 .U 90010627 .S J Lab Clin Med 9001; 114(4):431-8 .M Acids/*ME; Adult; Esophagus/*ME; Human; Peristalsis; Reference Values; Salivary Glands/PH; Salivation/*; Smoking/*; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Time Factors. .T The effect of cigarette smoking on salivation and esophageal acid clearance. .P JOURNAL ARTICLE. .W To further define the influence of cigarette smoking on the pathophysiology of gastroesophageal reflux disease, studies were done to evaluate acid clearance in the esophagus and the salivary titratable base secretion of chronic smokers as compared to those of nonsmokers, and to ascertain the acute effects of smoking on these variables. Eight nonsmoking volunteers and 16 cigarette smokers without symptoms of gastroesophageal reflux disease were studied. All studies were initiated after a 6-hour fast, with the smokers also having refrained from smoking. Of the 16 smokers half smoked three cigarettes in the course of the experiments and half did not smoke. The immediate effects of cigarette smoking were a prolongation of the acid clearance time and a diminution of the secretion of salivary titratable base. However, both of these effects were overshadowed by greater baseline differences between the populations of smokers and nonsmokers. As a population the smokers had only 60% of the titratable base secretion of nonsmokers and acid clearance times that were 50% longer than those of nonsmokers. These effects were presumably long-lasting effects of cigarette smoking, although the duration of the effect was not defined. The observed differences in acid clearance are most likely the result of diminished salivary base secretion, since good correlation existed between these parameters. .A Kahrilas PJ; Gupta RR. .I 201667 .U 90010749 .S J Intern Med 9001; 226(3):137-8 .M Denmark; Mass Media/*; Politics/*; Research/*. .T The scientific universe of the researcher, the media-person and the politician [editorial] .P EDITORIAL. .A Riis P. .I 201668 .U 90010751 .S J Intern Med 9001; 226(3):143-8 .M Adrenergic Beta Receptor Blockaders/*AD; Adult; Blood Pressure Determination; Echocardiography; Enalapril/*AD; Female; Heart Rate/DE; Hormones/BL; Human; Hypertension/BL/*DT; Male; Middle Age; Posture. .T Abrupt change from a beta-adrenoceptor blocking drug to enalapril in hypertension. .P JOURNAL ARTICLE. .W The haemodynamic and hormonal effects of an elective change of antihypertensive therapy from a beta-adrenoceptor blocking drug to a converting enzyme inhibitor, enalapril, were monitored in 12 hypertensive in-patients (WHO I). Blood pressure and heart rate were determined every 2-4 h using an automatic sphygmomanometer during an abrupt cessation of the previous beta-adrenoceptor blocking drug and commencement of treatment with enalapril 20 mg o.d. 12 h later. Mean blood pressure values at rest and during the hand grip test were lower when on enalapril, but heart rate was significantly higher, and three patients suffered from palpitations during the change. The change resulted in an improvement in cardiac function both at rest and during isometric work, as shown by echocardiography. A rapid decrease in plasma angiotensin converting enzyme (ACE) activity and an increase in renin activity were also seen after the change, while plasma levels of atrial natriuretic peptide (ANP) decreased towards normal values. The results suggest that an abrupt change from a chronic beta-adrenoceptor blocking drug to enalapril is safe, feasible and is likely to produce favourable haemodynamic and hormonal effects in hypertensive patients. .A Lilja M; Ikaheimo M; Juustila H; Pirttiaho H; Pakarinen A; Leppaluoto J; Jounela AJ; Ruskoaho H. .I 201669 .U 90010752 .S J Intern Med 9001; 226(3):149-55 .M Aorta, Abdominal/SU; Blood Vessel Prosthesis; Exertion; Female; Human; Intermittent Claudication/SU; Ischemia/*ME; Male; Middle Age; Muscles/*BS; Phosphates/*ME. .T Serum and urinary phosphate during and after prolonged muscular ischaemia in non-exercising men and women. .P JOURNAL ARTICLE. .W Serum inorganic phosphate (Pi) concentrations and urinary Pi excretions were measured in nine patients undergoing abdominal aortic bypass grafting (group I) and in nine patients undergoing lower limb arterial embolectomy (group II). In group I, serum Pi concentrations were normal until 24 h after reperfusion, when they decreased, reaching their nadir at 48 h (median Pi 0.45 mmol 1(-1). The urinary phosphate clearance relative to the creatinine clearance (Cp/Cc) increased 5 min after reperfusion reaching a maximal median value (0.454) in the 2-24-h collection period. In group II, eight patients had a normal and one had a subnormal serum Pi before reperfusion. None developed hypo- or hyperphosphataemia and the Cp/Cc remained unchanged. Daily urinary Pi excretion was higher in group I than in group II (P less than 0.03). The authors concluded that the regional muscular ischaemia in non-exercising men and women was not associated with hyperphosphataemia. The possible influence of major surgery and anaesthesia on phosphate homeostasis should be considered. .A Andersen PT; Nielsen LK; Hansen AK; Toft E; Jensen BV. .I 201670 .U 90010754 .S J Intern Med 9001; 226(3):163-70 .M Adult; Age Factors; Body Constitution/*; Female; Finland; Human; Male; Middle Age; Obesity/*EP; Sex Factors; Socioeconomic Factors. .T Changes in body mass index in a Finnish population between 1972 and 1982. .P JOURNAL ARTICLE. .W Population-based data on changes in body mass index are scarce. We have examined about 9700 people aged 30-59 years in two provinces of East Finland in 1972, 1977 and 1982. The age adjusted mean value of body mass index (kg m-2) in 1972 was 26.0 +/- 3.4 in men and 26.9 +/- 4.7 in women, increasing with age. During the 10-year follow-up the mean body mass index increased in men to 26.5 +/- 3.6 (P less than 0.001). In women we found a decrease in mean body mass index to 26.4 +/- 4.9 (P less than 0.001). The increase trend in body mass with age remained in women, while in men the age trend increased from survey to survey. The proportion of obese men also increased while in younger women a decrease was observed. The results of this study show the association between changes in physical activity, education etc. and the observed changes in the body mass index. .A Jalkanen L; Tuomilehto J; Nissinen A; Puska P. .I 201671 .U 90010757 .S J Intern Med 9001; 226(3):183-8 .M Blood Pressure/*; Creatinine/*BL; Glomerulonephritis/DI; Human; Kidney Failure, Chronic/BL/*DI/ET; Kidney, Polycystic/DI; Middle Age; Nephritis, Interstitial/DI; Proteinuria; Retrospective Studies. .T Factors influencing progression in patients with chronic renal failure. .P JOURNAL ARTICLE. .W To identify factors influencing the progression rate of chronic renal failure (CRF) in non-diabetics, the medical records of 124 patients with established CRF were reviewed retrospectively (serum creatinine between 200-350 mumols l-1 at the start of follow-up) for the period 1980-86. Sixteen patients were excluded because they did not fulfil the inclusion criteria. The remaining 108 patients were divided, using their original diagnosis, into four groups and were also assigned into one of three groups expressing their rate of progression. The definitions of these rates of progression were chosen arbitrarily. Comparisons with respect to mean arterial pressure (MAP), urinary protein excretion (UPE) and the progression rate of CRF were then made between the groups. In the group showing no progression of CRF (n = 17) there was a significantly lower MAP and UPE than in the two groups showing progression. Over all the patients and in the various diagnosis groups there was a strong correlation between UPE and the progression rate of CRF. There was no significant correlation between MAP and the progression rate of CRF in the diagnosis groups. These results indicate that an increasing magnitude of proteinuria is an adverse prognostic factor in CRF, irrespective of aetiology, and support the view that excessive glomerular protein filtration leads to glomerulosclerosis. .A Stenvinkel P; Alvestrand A; Bergstrom J. .I 201672 .U 90010758 .S J Intern Med 9001; 226(3):189-94 .M Adult; Aged; Amino Acids, Sulfur/*ME; Cysteine/BL; Female; Hemodialysis; Human; Kidney Failure, Chronic/DH/*ME/TH; Male; Methionine/BL; Middle Age; Muscles/*ME; Support, Non-U.S. Gov't; Taurine/*ME. .T Sulphur amino acids in plasma and muscle in patients with chronic renal failure: evidence for taurine depletion. .P JOURNAL ARTICLE. .W The sulphur amino acids methionine, cysteine (1/2-cystine) and taurine were determined by ion-exchange chromatography in plasma and muscle biopsy material obtained from 46 patients with chronic renal failure. Twelve patients were untreated, eight patients were treated with a low protein diet supplemented with essential amino acids, 11 patients treated with maintenance haemodialysis and 15 patients with continuous ambulatory peritoneal dialysis (CAPD). Patient data were compared to data obtained from 18 healthy subjects. Plasma cysteine was elevated in the untreated patients, in the patients treated with low protein diet and in the maintenance haemodialysis patients. Muscle methionine was significantly elevated in the CAPD patients. Plasma taurine was decreased in the untreated patients and in the CAPD patients and muscle taurine was borderline low in the untreated patients and significantly decreased in the other patient groups. The results show that taurine depletion may occur in patients with chronic uraemia despite normal or elevated concentrations of precursor sulphur amino acids, suggesting inhibited synthesis or enhanced degradation of taurine in the uraemic state. .A Bergstrom J; Alvestrand A; Furst P; Lindholm B. .I 201673 .U 90010760 .S J Intern Med 9001; 226(3):201-3 .M Adolescence; Adult; Aged; Female; Human; Male; Middle Age; Neoplasms/*CO/EP; Nephrotic Syndrome/*CO/PA; Retrospective Studies; Support, Non-U.S. Gov't. .T The occurrence of malignant disease in adult nephrotic syndrome. .P JOURNAL ARTICLE. .W The aim of the present study was to determine the incidence of malignant disease (MD) in adult patients with nephrotic syndrome (NS). Eighty-eight consecutive patients (38 females; 50 males; mean age 47 years; range 15-86) seen in a renal clinic in a 13-year period with NS were studied. Eight of the patients had or developed MD. One patient had MD (medullary thyroid carcinoma) and NS diagnosed concomitantly and two patients had MD (both malignant lymphoma) diagnosed 19 and 21 months after the diagnosis of NS, respectively. In conclusion, only few patients in a renal clinic at debut of NS do have a simultaneous MD. Furthermore, their risk of developing such a disease is at worst only slightly raised. .A Lund L; Jacobsen BA; Schmidt EB. .I 201674 .U 90010761 .S J Intern Med 9001; 226(3):205-7 .M Addison's Disease/*CO; Case Report; Cerebral Arteries/PA; Diagnosis, Differential; Female; Human; Lymphoma/*CO; Middle Age; Temporal Arteritis/DI/*ET. .T Addison's disease, malignant lymphoma and death from cerebral giant cell arteritis. .P JOURNAL ARTICLE. .W A 61-year-old woman with Addison's disease and malignant lymphoma for several years was admitted to hospital with a 2-month history of fatigue and a 7 kg weight loss. The erythrocyte sedimentation rate was 92 mm h-1 and a temporal biopsy was performed as a part of the clinical investigation. She suddenly suffered a paresis of the right arm, sudden blindness and her blood pressure fell to 100/60 mmHg. Hydrocortisone was given intravenously followed by betamethasone, and an Addison crisis as well as a giant cell arteritis (GCA) was suspected. Activity in the malignant lymphoma was also a possibility. The patient did not improve and died 8 d later. The temporal biopsy indicated GCA. The autopsy showed a pronounced intimal inflammatory reaction of the intracerebral arteries and an infarction in the left posterior hemisphere. A possible link between GCA and other autoimmune diseases is discussed. .A Landin K; Bengtsson BA; Wilhelmsen L. .I 201675 .U 90010819 .S J Fam Pract 9001; 29(4):359-60 .M Animal; Female; Gardnerella vaginalis/IP; Gentian Violet; Haemophilus Infections/*DI; Human; Phenazines; Vaginitis/*DI. .T Diagnostic criteria for bacterial vaginosis [letter; comment] .P COMMENT; LETTER. .A Mengel MB. .I 201676 .U 90010820 .S J Fam Pract 9001; 29(4):360 .M Abbreviations/*; Delivery/*MT; Female; Obstetrical Forceps/*. .T Forceps delivery [letter] .P LETTER. .A Bachman JW. .I 201677 .U 90010821 .S J Fam Pract 9001; 29(4):361, 443 .M Family Practice/*TD; Obstetrics/*; Physician's Practice Patterns/*TD. .T Obstetrics in family practice [letter; comment] .P COMMENT; LETTER. .I 201678 .U 90010822 .S J Fam Pract 9001; 29(4):363-6 .M Adult; Asthma/ET/*PX/TH; Bronchodilator Agents/*TU; Case Report; Family; Female; Human; Psychophysiologic Disorders/ET/*TH; Rejection (Psychology); Stress, Psychological/CO. .T Asthma--a therapeutic challenge [clinical conference] .P JOURNAL ARTICLE. .A Kearl GW; Tarleton K. .I 201679 .U 90010824 .S J Fam Pract 9001; 29(4):372-6 .M Bacteriuria/CO/*DI/EC; Costs and Cost Analysis; Decision Trees/*; Female; Hospitalization/EC; Human; Pregnancy; Pregnancy Complications, Infectious/DI/*EC; Pyelonephritis/EC/ET. .T Screening for asymptomatic bacteriuria in pregnancy. A decision and cost analysis [see comments] .P JOURNAL ARTICLE. .W Screening women for asymptomatic bacteriuria on the first prenatal visit is a standard of obstetric care. Treating women with positive results decreases the risk of pyelonephritis and possible prematurity. This study uses decision and cost analysis to compare the utility of screening for asymptomatic bacteriuria with not screening. Data are based on published reports and average charges for services. Costs are based on 1988 charges, projected for the expected results of outpatient screening, possible suppressive therapy, and risks of pyelonephritis. Screening is based on the combined sensitivities and specificities of the MacConkey and CLED (cysteine-lactose-electrolyte-deficient agar) panels of the dip-slide culture. Under the baseline assumptions, the risk of pyelonephritis is estimated to be 2 cases per 100 screened women vs 3.5 cases per 100 unscreened women. The anticipated cost of screening 100 women is $9,939, compared with $12,824 for not screening 100 women. Screening is cost saving unless the cost of screening is above $26, the length of hospitalization for pyelonephritis is fewer than 2.2 days, the risk of asymptomatic bacteriuria falls below 2%, the risk of pyelonephritis with asymptomatic bacteriuria falls below 13%, or the efficacy of treatment in preventing pyelonephritis falls below 38%. .A Wadland WC; Plante DA. .I 201680 .U 90010826 .S J Fam Pract 9001; 29(4):382-6 .M Abdominal Pain/*ET; Adolescence; Adult; Female; Hospitalization; Human; Male; Medical Records; Middle Age; Nausea/*ET; Retrospective Studies; Thyrotoxicosis/*CO/DI/PP; Vomiting/*ET. .T Vomiting, nausea, and abdominal pain: unrecognized symptoms of thyrotoxicosis. .P JOURNAL ARTICLE. .W The prevalence of symptoms in thyrotoxicosis at the time of diagnosis has received little attention in studies of this condition. Vomiting, nausea, and abdominal pain have not been included as common presenting symptoms for thyrotoxicosis in standard textbooks of medicine and endocrinology. Some reports in the medical literature, however, indicate that these abdominal symptoms may be important manifestations of this condition. A retrospective chart review was undertaken to determine the prevalence of vomiting, nausea, and abdominal pain in patients hospitalized for thyrotoxicosis at Louisiana State University Medical Center, Shreveport, from 1982 through 1986. Of 25 thyrotoxic patients who had thyrotoxicosis diagnosed during or immediately prior to admission, 44% reported vomiting, 28% reported nausea, and 20% complained of abdominal pain. One or more of these abdominal symptoms were included as a chief complaint in 36% of cases reviewed. Further study of the clinical presentation of thyrotoxicosis in the outpatient setting is needed to improve the timeliness and cost effectiveness of the clinical diagnosis of this condition. .A Harper MB. .I 201681 .U 90010827 .S J Fam Pract 9001; 29(4):389-95; discussion 395-6 .M Adolescence; Adult; Blood Glucose/*; Female; Glucose Tolerance Test; Human; Middle Age; Pregnancy; Pregnancy in Diabetes/*BL/CO; Pregnancy Outcome/*; Retrospective Studies; Support, Non-U.S. Gov't. .T No relationship between pregnancy complications and variations in blood glucose levels among nondiabetic women. .P JOURNAL ARTICLE. .W Research using high-risk pregnant women suggests that postprandial blood glucose levels at the high end of normal are associated with greater risk of adverse pregnancy outcomes than low-normal levels. The objective of this study was to determine the relationships between pregnancy complications and glucose levels in low-risk pregnant women. Based on 2-hour postprandial glucose testing at 27 to 33 weeks, 337 women with normal reproductive histories were divided into three groups: group A, glucose less than 5.6 mmol/L (100 mg/dL), group B, 5.6 to 6.6 mmol/L (100 to 119 mg/dL), and group C, 6.7 to 9.1 mmol/L (120 to 164 mg/dL). Women with glucose levels greater than or equal to 9.2 mmol/L (165 mg/dL) were excluded. The groups were compared to detect differences in rates of various maternal outcomes (preeclampsia, cesarean delivery, forceps delivery) and neonatal outcomes (macrosomia, Apgar scores, prematurity, fetal death, infant death, congenital anomalies). No significant differences were found. These data indicate that variations in maternal glucose tolerance (within the normal range) are not associated with adverse outcomes in normal pregnant women. .A Weiss BD; Senf JH; Udall W. .I 201682 .U 90010828 .S J Fam Pract 9001; 29(4):397-400 .M Child; Child, Preschool; Chronic Disease/*; Family/*PX; Grief/*; Human; Physician's Role; Recurrence. .T The chronically ill child and recurring family grief. .P JOURNAL ARTICLE. .W Chronically ill children and their families are increasingly seen in health care practices as the incidence of infant mortality and formerly fatal childhood diseases has decreased. These children present special challenges to the physician's perceived role as healer. Unlike the sequenced predictable stages of grief that families go through in facing terminal illness, the grief experienced by parents of the chronically ill is recurrent and cyclical. The physician who understands and can anticipate the causes and nature of this grief will be subject to less frustration in treating these children and their families and will be able to offer them more effective care. .A Worthington RC. .I 201683 .U 90010829 .S J Fam Pract 9001; 29(4):401-5 .M Adolescence; Adult; Aged; Attitude; Child; Child, Preschool; Counseling/*MT; Evaluation Studies; Family/*; Human; Infant; Infant, Newborn; Middle Age; Physician's Role/*; Prospective Studies; Role/*; Social Support; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Family conferences: reasons, levels of involvement and perceived usefulness. .P JOURNAL ARTICLE. .W In this study, family conferences conducted in a family practice model clinic were prospectively monitored. Study goals were (1) to identify the distribution of clinical situations for which family conferences were being conducted, (2) to test whether the levels of physician involvement typology developed by Doherty and Baird represented a hierarchy of skills, at least in their frequency of application in conferences, and (3) to generate clinicians' estimates of conference utility. During a 1-month period 57 conferences were held, primarily for medical management problems. Sixty-one percent took place in the model clinic (3% of office visits) and 23% in the hospital (20% of admissions). A hierarchy of levels of involvement was found: the clinicians indicated that medical information and advice was most often provided "a lot," emotional support was provided "some," systematic assessment and intervention were provided "a little," and family therapy skills were usually not used. Clinicians perceived the conferences to be usually useful to the patient, almost always useful to the family, and always useful to themselves. These results can provide information for future training, practice, and research. .A Meyer DL; Schneid JA; Craigie FC Jr. .I 201684 .U 90010830 .S J Fam Pract 9001; 29(4):406-9 .M Attitude of Health Personnel; Bladder/DE; Cardiovascular System/DE; Central Nervous System/DE; Climacteric/DE; Estrogen Replacement Therapy/*; Female; Human; Menopause/*PH; Osteoporosis, Postmenopausal/ET/PC; Skin/DE. .T Is routine use of estrogen indicated in postmenopausal women? An affirmative view. .P JOURNAL ARTICLE. .W A study of age-adjusted all causes of mortality has shown that estrogen nonusers are three times as likely to die of all causes compared with users. The benefit of estrogen is greatest in women who have had their ovaries removed, but benefit also occurs in those who have had a hysterectomy as well as those with intact pelvic organs. A recent British study also reported that women taking estrogen were less likely to die of all causes. Because of the many benefits of estrogen replacement therapy improving both the quality and quantity of life, all women who have this postmenopausal hormone deficiency, except possibly those who are obese, should receive estrogen replacement. The beneficial effects of estrogen replacement therapy are many and there are very few adverse effects. .A Mishell DR Jr. .I 201685 .U 90010831 .S J Fam Pract 9001; 29(4):410-5 .M Aging/*PH; Attitude of Health Personnel; Estrogen Replacement Therapy/*; Exercise; Female; Human; Menopause/*PH; Middle Age; Nutrition; Osteoporosis, Postmenopausal/ET/PC; Quality of Life. .T Is routine use of estrogen indicated in postmenopausal women? An opposing view. .P JOURNAL ARTICLE. .A Notelovitz M. .I 201686 .U 90010832 .S J Fam Pract 9001; 29(4):416-21 .M Ambulatory Care/*MT; Continuity of Patient Care/*; Family/*; Family Practice/*ED; Female; Human; Male; Preceptorship; Primary Health Care/*. .T Continuity, family involvement, and clinical content in a year-long ambulatory care clerkship. .P JOURNAL ARTICLE. .W Entries in student logbooks for the Ambulatory Care Clerkship at the Michigan State University College of Human Medicine were tabulated by microcomputer for 38,430 patient encounters in five community campuses in 1985 and 1986, and by hand for 32,182 patient encounters in Grand Rapids from 1983 to 1987. The repeat visit rate recorded toward the end of the clerkship by students in family practice settings was approximately 60% of the rate recorded by students taking the clerkship with internists or pediatricians. Students in family practice and in pediatrics had the same degree of exposure to patient families; however, family exposure in internal medicine and in pediatrics was limited to other family members of the same generation as the patient. Distributions of the kinds of patient problems seen were distinctive by specialty and were stable across 5 years. .A Smith BW; Eary LE; Ruane TJ; Hough DO. .I 201687 .U 90010834 .S J Fam Pract 9001; 29(4):433-5 .M Antibiotics/TU; Case Report; Diagnosis, Differential; Female; Hordeolum/*CO/DT; Human; Middle Age; Septicemia/DT/*ET; Staphylococcal Infections/DT/*ET. .T Staphylococcus aureus hordeolum as a cause of bacteremia and secondary foci. .P JOURNAL ARTICLE. .A Zimmerman RK. .I 201688 .U 90010835 .S J Fam Pract 9001; 29(4):437-8 .M Community Health Centers; Family Practice/*ED; Internship and Residency; Sigmoidoscopy/*. .T Family practice residency program tutoring of community-based practitioners in flexible sigmoidoscopy. .P JOURNAL ARTICLE. .A Glinka SJ. .I 201689 .U 90010836 .S J Fam Pract 9001; 29(4):440-1 .M Family Practice/*; Female; Human; Internship and Residency/*; Male; North Carolina; Personnel Management; Personnel Selection/*MT; Professional Practice Location; Questionnaires. .T Recruitment of 1988 graduates of North Carolina family practice residencies. .P JOURNAL ARTICLE. .A Williams JJ. .I 201690 .U 90010837 .S J Fam Pract 9001; 29(4):443 .M Ethics, Medical/*; Family Practice/*. .T Ethics of gatekeeper role [letter] .P LETTER. .A Brody H. .I 201691 .U 90010995 .S J Nerv Ment Dis 9001; 177(10):593-606 .M Colombia; Demography; Follow-Up Studies; Forecasting; Human; Interviews; Length of Stay; Models, Psychological; Schizophrenia/DI; Schizophrenic Psychology/*; Social Adjustment; Statistics; Support, Non-U.S. Gov't; Time Factors. .T Clinical course and outcome of schizophrenia in Cali, Colombia. A 10-year follow-up study. .P JOURNAL ARTICLE. .W The present paper is a very succinct description of the findings from the 10-year follow-up of a group of 101 patients from Cali, Colombia who were included in the WHO International Pilot Study of Schizophrenia. It is based on a prospective study conducted with the use of standardized instruments and with clinical evaluations performed by the same examiners at the beginning and end phases. A classification of the varieties of clinical course observed throughout the 10-year period is presented, as well as a description of several aspects of the social and clinical condition of cases at the time of the last observation. The possibility of finding predictors of the outcome of the disorder is explored through the use of multivariate methods, and a series of comments and conclusions is formulated. .A Leon CA. .I 201692 .U 90010997 .S J Nerv Ment Dis 9001; 177(10):616-23 .M Comparative Study; Factor Analysis, Statistical; Fantasy; Fetishism (Psychiatric); Gender Identity/*; Homosexuality/PX; Human; Identification (Psychology)/*; Male; Paraphilias/*PX; Questionnaires. .T The concept of autogynephilia and the typology of male gender dysphoria. .P JOURNAL ARTICLE. .W This study tested the hypothesis that all gender-dysphoric males who are not sexually aroused by men (homosexual) are instead sexually aroused by the thought or image of themselves as women (autogynephilic). Subjects were 212 adult male-to-female transsexuals. These were divided into four groups; one homosexual and three nonhomosexual. The three nonhomosexual groups were heterosexual, bisexual, and analloerotic (unattracted to male or female partners, but not necessarily devoid of all erotic behavior). A Core Autogynephilia Scale was developed to assess a subject's propensity to be sexually aroused by the fantasy of being a woman. The four transsexual groups were compared on this measure (and on several others), using Newman-Keuls multiple-range tests at p less than .05. As predicted, all three nonhomosexual groups were more likely than the homosexual group to report sexual stimulation by cross-gender fantasy. This finding supports the hypothesis that the major types of nonhomosexual gender dysphoria constitute variant forms of one underlying disorder, which may be characterized as autogynephilic gender dysphoria. .A Blanchard R. .I 201693 .U 90010998 .S J Nerv Ment Dis 9001; 177(10):624-31 .M Adaptation, Psychological/*; Adult; Comparative Study; Female; Human; Marriage; Mastectomy/*; Middle Age; Postoperative Period; Social Adjustment/*; Social Support. .T Psychosocial adjustment to a mastectomy. .P JOURNAL ARTICLE. .W Increasing attention is being given to treating the psychosocial as well as the physical needs of mastectomy patients. The present study investigated and endeavored to quantify the psychological, sexual, and social adjustment reactions to a mastectomy, the possible interaction of these reactions, and the role of environmental support in mediating these responses. Forty married and 37 unmarried mastectomy patients completed a battery of tests, including the Body-Cathexis/Self-Cathexis Scale, SCL-90, Derogatis Sexual Functioning Inventory, Social Adjustment Scale-Self-Report, Perceived Social Support Scale, and a Support Questionnaire. Overall findings indicated that a mastectomy has the potential for affecting psychological, sexual, and social adjustment for at least a limited time post-operatively. Specifically, significant correlations were found between psychological, sexual, and social adjustment. Significant differences were also demonstrated in the married/nonmarried comparison. Additionally, results emphasized the importance of environmental support for postoperative adjustment. .A Jones DN; Reznikoff M. .I 201694 .U 90010999 .S J Nerv Ment Dis 9001; 177(10):632-7 .M Anorexia Nervosa/TH; Behavior Therapy; Bulimia/TH; Consumer Satisfaction/*; Counseling; Eating Disorders/*TH; Female; Human; Nutrition; Patient Acceptance of Health Care/*; Psychotherapy; Psychotherapy, Group; Support, Non-U.S. Gov't. .T Help seeking and satisfaction with care in 641 women with eating disorders. I. Patterns of utilization, attributed change, and perceived efficacy of treatment. .P JOURNAL ARTICLE. .W Help-seeking patterns and satisfaction with care were described by 641 women with eating disorders participating in a national magazine survey. Between 60.6% and 92.9% of respondents in three diagnostic groups sought professional treatment. Professional treatments most often entered were individual psychotherapy (52.9%), behavioral therapy (28.0%), group therapy (24.6%), and nutritional therapy (18.6%). Treatments were generally seen as helping "a little." Only bulimic anorexia nervosa respondents perceived any interventions to be more harmful than helpful, specifically Overeaters Anonymous and self-help groups, both nonprofessional interventions. Caregivers selected as "experts" regarding eating disorders were rated as more efficacious than others, helping "a little" to "somewhat." .A Yager J; Landsverk J; Edelstein CK. .I 201695 .U 90011000 .S J Nerv Ment Dis 9001; 177(10):638-42 .M Acute Disease; Adult; Cohort Studies; Demography; Human; Length of Stay; Lithium/TU; Manic Disorder/*DT/PX; Multivariate Analysis; Psychiatric Status Rating Scales. .T Demographic and clinical features predictive of recovery in acute mania. .P JOURNAL ARTICLE. .W Discrepancies exist in previous reports regarding clinical and demographic features associated with recovery in acute mania. The authors studied 44 hospitalized patients with bipolar affective disorder, manic type. They report a significant association between more depressive symptomatology and perhaps younger age of illness onset, and poor immediate treatment response. They also found the total amount of psychopathology at admission, as measured by the Brief Psychiatric Rating Scale and Manic State Rating Scale, and the degree of psychosis to be unrelated to immediate outcome. The authors suggest that the not recovered manic subgroup has a distinct illness or a variant of bipolar disorder with poor prognosis that warrants further and separate investigation. .A Cohen S; Khan A; Cox G. .I 201696 .U 90011085 .S J Neurol Neurosurg Psychiatry 9001; 52(10):1121-7 .M Adolescence; Adult; Aged; Antibodies/AN; Child; Child, Preschool; Female; Follow-Up Studies; Human; Infant; Infant, Newborn; Male; Middle Age; Muscles/PA; Myasthenia Gravis/*/EP/IM/PA; Netherlands. .T The natural course of myasthenia gravis: a long term follow up study. .P JOURNAL ARTICLE. .W A long term follow up study is presented of 73 patients with myasthenia gravis, living in Amsterdam between 1926 and 1965. In the period 1961-65 the annual incidence was 3.1, the prevalence 53 per million. Maximum severity of the disease occurred during the first seven years after onset in 87%. Eighteen (29%) patients died, of whom eight had a thymoma (TH). Spontaneous improvement or remission occurred at any time during the follow up. At the end of the study (1985) 16 (22%) patients were in a complete clinical remission, 13 (18%) had improved considerably (3 with prednisone), 12 (16%) had improved moderately, 12 (16%) had remained unchanged and two had deteriorated. If the early deaths are excluded the outcome is similar in the early and the late onset group without TH. Patients with TH had a less favourable course. Associated autoimmune diseases were diagnosed in 25% (n = 58). Because most of these patients were treated with anticholinesterases only, the evolution of their clinical state represents the natural course of MG. .A Oosterhuis HJ. .I 201697 .U 90011086 .S J Neurol Neurosurg Psychiatry 9001; 52(10):1128-34 .M Adolescence; Adult; Brain Injuries/*PX; Female; Head Injuries/*PX; Human; Male; Middle Age; Social Adjustment/*; Support, Non-U.S. Gov't; Trauma Severity Indices; Wounds, Nonpenetrating/*PX. .T Psychosocial outcome for the survivors of severe blunt head injury: the results from a consecutive series of 100 patients. .P JOURNAL ARTICLE. .W A consecutive series of 100 severely blunt head injured subjects was followed up six years after trauma and the level of psychosocial reintegration was determined for 87 subjects. Three-quarters of the series were classified as demonstrating major disability, having either a Poor Reintegration (33%) or a Substantially Limited Reintegration (43%); the remaining one-quarter of the series attained a Good Reintegration. The level of reintegration was related to the Glasgow Outcome Scale classification, although a one-to-one correspondence between the Glasgow Outcome Scale and the Psychosocial Disability Scale was not found: each of the Moderate Disability and Good Recovery groups was fairly evenly divided between a better and worse level of reintegration. Specific aspects of the subjects' psychosocial reintegration in employment, interpersonal relationships, functional independence, social contacts and leisure interests are described and the implications of the findings for the provision of extended care services to meet the long term needs are discussed. .A Tate RL; Lulham JM; Broe GA; Strettles B; Pfaff A. .I 201698 .U 90011087 .S J Neurol Neurosurg Psychiatry 9001; 52(10):1135-40 .M Adolescence; Adult; Aged; Cerebral Aneurysm/*PX/SU; Cerebral Arteries; Female; Human; Male; Middle Age; Nervous System/*PP; Neuropsychological Tests/*; Prognosis; Time Factors. .T Neuropsychological outcome of patients operated upon for an intracranial aneurysm: analysis of general prognostic factors and of the effects of the location of the aneurysm. .P JOURNAL ARTICLE. .W One hundred and fourteen patients operated on for an intracranial aneurysm were followed up in order to investigate their neuropsychological outcome and to detect if there were any clinical features assessed around the time of operation that had prognostic significance. The neuropsychological examination evaluated language, apraxia, memory, intelligence and spatial ability. In the statistical analysis the overall severity of neuropsychological disorder was studied. "Late surgery timing" had a negative influence upon the neuropsychological outcome. There was not a difference between different aneurysm sites. Several patients with an apparently good clinical outcome showed neuropsychological deficits. Neuropsychological assessment is important in the evaluation of outcome after subarachnoid haemorrhage. .A Desantis A; Laiacona M; Barbarotto R; Basso A; Villani R; Spagnoli D; Capitani E. .I 201699 .U 90011088 .S J Neurol Neurosurg Psychiatry 9001; 52(10):1141-8 .M Adenosine Triphosphatase, Myosin/PH; Adult; Aged; Female; Human; Male; Middle Age; Motor Neurons/*PH; Muscles/PA/*PP; Poliomyelitis/PA/*PP; Support, Non-U.S. Gov't. .T Motoneuron firing and isomyosin type of muscle fibres in prior polio. .P JOURNAL ARTICLE. .W In patients with prior polio there was an excessive use of remaining motor units and an absence of type II muscle fibres in the tibialis anterior (TA). In the present study, eight subjects with prior polio with more than 90% type I fibres in the TA were examined. The aim was to elucidate whether the lack of type II muscle fibres was due to a selective loss of motoneurons with high threshold and high axonal conduction velocity or due to a muscle fibre transition from type II to type I. There was no decrease of the proportion of motoneurons with high threshold and high axonal conduction velocity. Monoclonal antibodies against fast and slow myosin heavy chains (MHC) were used as histochemical markers and many muscle fibres of type I according to ATPase stainability showed a binding of both anti-fast and anti-slow MHC. It is suggested that the type I muscle fibre dominance in prior polio subjects with excessive use of TA during walking is due to a muscle fibre transition from type II to type I and not to a loss of one class of motor units. .A Borg K; Borg J; Dhoot G; Edstrom L; Grimby L; Thornell LE. .I 201700 .U 90011089 .S J Neurol Neurosurg Psychiatry 9001; 52(10):1149-56 .M Action Potentials; Adult; Electric Stimulation; Facial Muscles/*PH; Facial Nerve/*PH; Facial Paralysis/PP; Female; Human; Magnetics; Male; Motor Cortex/*PH; Neural Pathways/PH; Support, Non-U.S. Gov't. .T Investigation of facial motor pathways by electrical and magnetic stimulation: sites and mechanisms of excitation. .P JOURNAL ARTICLE. .W A refined technique is described for non invasive examination of the facial motor pathways by stimulation of the extra- and intracranial segment of the facial nerve and the facial motor cortex. Surface recordings from the nasalis muscle rather than from the orbicularis oris muscle were used, since the compound muscle action potential (CMAP) from this muscle showed a more clearly defined onset. Electrical extracranial stimulation of the facial nerve at the stylomastoid fossa in 14 healthy subjects yielded a mean distal motor latency of 3.7 ms (SD 0.46), comparable with reported latencies to the orbicularis oris muscle. Using a magnetic stimulator, transcranial stimulation of the facial nerve was performed. The mechanism of transcranial magnetic facial nerve stimulation was studied using recordings on 12 patients who had facial nerve lesions at different locations, and with intraoperative direct measurements in four patients undergoing posterior fossa surgery. The actual site of stimulation could be localised to the proximal part of the facial canal, and a mean "transosseal conduction time" of 1.2 ms (SD 0.18) was calculated. The cerebrospinal fluid (CSF) played an important role in mediating the magnetically induced stimulating currents. Finally, with transcranial magnetic stimulation of the facial motor cortex, clearly discernible CMAPs could be produced when voluntary activation of several facial muscles was used to facilitate the responses. From this, a central motor conduction time of 5.1 ms was calculated (SD 0.60, 6 subjects). .A Rosler KM; Hess CW; Schmid UD. .I 201701 .U 90011090 .S J Neurol Neurosurg Psychiatry 9001; 52(10):1157-61 .M Adult; Aged; Brain Stem; Evoked Potentials, Auditory; Evoked Potentials, Visual; Eye Movements/*; Female; Human; Male; Middle Age; Multiple Sclerosis/DI/PP; Saccades/*; Spinal Cord Diseases/*DI/PP. .T The value of measuring saccadic eye movement in the investigation of non-compressive myelopathy. .P JOURNAL ARTICLE. .W Saccadic eye movement recording was performed in 53 patients with non-compressive myelopathy. Twenty one patients (40%) had subclinical abnormalities of saccadic movement, supporting a diagnosis of probable multiple sclerosis. When used in addition to the measurement of visual evoked potentials and brainstem auditory evoked responses, the detection of subclinical abnormalities increased from 40% to 57%. The detection rate of abnormalities by saccadic eye movement recording was equal to that of visual evoked responses, but more than of brainstem auditory evoked responses. Prolonged latency of gaze was the most common saccadic latency abnormality detected. The majority of saccadic velocity abnormalities could be explained by disease in the medial longitudinal bundle. An unusual finding was that abduction velocity was increased in six patients. It is concluded that the simple measurement of saccadic eye movement is a valuable addition to other ancillary investigations for the diagnosis of multiple sclerosis. It also allows analysis of oculomotor function, commonly disordered in multiple sclerosis, but rarely investigated. .A Pitt MC; Rawles JM. .I 201702 .U 90011091 .S J Neurol Neurosurg Psychiatry 9001; 52(10):1162-9 .M Adolescence; Adult; Brain Injuries/CO/PA/*PP; Dichotic Listening Tests/*; Female; Hand; Hearing Disorders/ET; Hearing Tests/*; Human; Male; Middle Age; Psychomotor Performance/*; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Touch. .T Dichotic listening and manual performance in relation to magnetic resonance imaging after closed head injury. .P JOURNAL ARTICLE. .W In order to investigate post-traumatic hemispheric disconnection effects, dichotic listening and intermanual tasks were administered to 69 patients who had sustained a closed head injury of varying severity. The manual tasks consisted of naming objects palpated in either hand, transfer of postures from one hand to the other and writing. Consistent with predictions, the degree of ear asymmetry in dichotic listening performance was directly related to the severity of the head injury as reflected by the degree of impaired consciousness. Depth and localisation of parenchymal lesion characterised by magnetic resonance imaging were also related to the degree of ear asymmetry. Parenchymal lesions situated in sites which could potentially interfere with callosal auditory or geniculocortical pathways produced a greater disparity in response to left versus right ear inputs as compared with parenchymal lesions in areas such as the frontal lobes which are purportedly unrelated to asymmetries in dichotic listening performance. The results provide further evidence for the effects of multifocal brain lesions involving the white matter on tasks which require intra and/or interhemispheric integration. .A Levin HS; High WM Jr; Williams DH; Eisenberg HM; Amparo EG; Guinto FC Jr; Ewert J. .I 201703 .U 90011092 .S J Neurol Neurosurg Psychiatry 9001; 52(10):1170-5 .M Adolescence; Adult; Aged; Child; Contrast Media/AD/*AE; Female; Human; Injections, Intravenous; Male; Middle Age; Seizures/*CI; Tomography, X-Ray Computed. .T Seizures after intravenous contrast media for cranial computed tomography. .P JOURNAL ARTICLE. .W Patients who had contrast medium-induced seizures were reviewed retrospectively in a consecutive series of 15,226 contrast-enhanced head CT examinations. An incidence of 0.19% was found. There was a strong association with a history of spontaneous seizure and with the presence of a structural intracranial abnormality. The contrast medium-induced seizures were short-lived and self-limiting or readily controlled with small doses of intravenous diazepam. They were clinically benign. .A Nelson M; Bartlett RJ; Lamb JT. .I 201704 .U 90011093 .S J Neurol Neurosurg Psychiatry 9001; 52(10):1176-81 .M Action Potentials; Adult; Aged; Arteriovenous Malformations/*PP; Female; Human; Male; Middle Age; Spinal Cord/*BS. .T Electrophysiological signs of arteriovenous malformations of the spinal cord. .P JOURNAL ARTICLE. .W A characteristic pattern of electrophysiological changes was found in 24 patients with confirmed spinal cord arteriovenous malformations (AVMs). The AVMs were limited to the thoracic cord in seven, involved the conus and the cauda equina in 10, and involved all levels in six. Of the patients, 88% had at least one definite electrophysiological abnormality: nerve conduction studies showed abnormal results in 43% (10 of 23), needle electromyography in 77% (17 of 22), and tibial somatosensory evoked potentials in 88% (7 of 8). The pattern of involvement was of scattered, multiple, bilateral thoracolumbosacral radiculopathies, consistent with axonal or neuronal destruction, associated with paraspinal fibrillations or abnormal activation of motor unit potentials. Electrophysiological abnormalities were seen in most patients with lower motor neuron clinical deficit. These abnormalities depended on the caudal extension of the AVM, on an arterial supply at T-10 or below, and on the duration of symptoms. In addition to the expected abnormalities in the distribution of the AVM location, four patients had electrical changes at a distance, which may have been due to venous stasis. .A Armon C; Daube JR. .I 201705 .U 90011094 .S J Neurol Neurosurg Psychiatry 9001; 52(10):1182-4 .M Brain Stem/PH; Case Report; Electric Stimulation Therapy/*; Human; Male; Middle Age; Stuttering/*TH; Thalamus/*/PH. .T Alleviation of acquired stuttering with human centremedian thalamic stimulation [see comments] .P JOURNAL ARTICLE. .W Despite many investigations, the cerebral mechanism for stuttering remains unknown. Recently, increased attention has been paid to acquired stuttering of adult onset in the hope that the events associated with it might provide clues to the biological mechanism underlying stuttering. This attention has focused exclusively on the cortical substrates. We present our observations of acquired dysfluency, presumably of subcortical origin in a neurosurgical subject with intractable pain. The stuttering was relieved by thalamic electric stimulation. The effect of thalamic stimulation on the stuttering suggests that the pathophysiology of transient asynchronisation in the balancing and sequencing of multiple impulses is amenable to a diffusely orchestrated functional tuning of the thalamic and brainstem implicated subcortical structures and pathways. .A Bhatnagar SC; Andy OJ. .I 201706 .U 90011095 .S J Neurol Neurosurg Psychiatry 9001; 52(10):1185-7 .M Adult; Brain/*RA; Brain Diseases/CO/*RA; Epilepsy/ET/*RA; Female; Human; Male; Middle Age; Tomography, X-Ray Computed. .T Appearing and disappearing CT scan abnormalities in epilepsy in India--an enigma. .P JOURNAL ARTICLE. .W In 230 consecutive cases of epilepsy, CT abnormalities were found in 51.7%. Out of these, 91 cases (39.5%) had non specific abnormalities consisting mostly of ring lesions, hyperdense disc lesions with surrounding oedema in enhanced scans and in a small percentage hypodense lesions, generalised brain oedema and calcifications. All these cases were treated with anticonvulsant drugs alone. A follow up scan was possible in 31 cases, 12 weeks or later, after the control of the seizures. Out of these 31 cases, 24 showed a complete or significant resolution and five remained unchanged. Two of these cases showed an increase in the lesions which resolved on treatment with antituberculous drugs. These lesions therefore may have an aetiology other than tuberculosis in the majority of cases and there is ample justification in treating them initially with anticonvulsant drugs only. .A Bansal BC; Dua A; Gupta R; Gupta MS. .I 201707 .U 90011096 .S J Neurol Neurosurg Psychiatry 9001; 52(10):1188-90 .M Adult; Aged; Aged, 80 and over; Cerebral Hemorrhage/CO; Cerebral Infarction/*ET; Female; Human; Hypertension/CO; Male; Middle Age; Prospective Studies; Risk Factors. .T Non ischaemic causes of lacunar syndromes: prevalence and clinical findings [see comments] .P JOURNAL ARTICLE. .W To evaluate the prevalence of lacunar syndromes due to non ischaemic causes 97 consecutive patients with recent (less than 72 hours) onset of a recognised lacunar syndrome were studied. Investigations showed that nine cases were due to non ischaemic pathologies (four primary intracerebral haemorrhages, one rupture of a mycotic aneurysm, one cerebral abscess, one subdural haematoma, one glioblastoma, one multiple sclerosis). Clinical features did not allow a separation of non ischaemic from ischaemic patients; however, hypertension was significantly more frequent in the latter group, and its positive predictive value in identifying ischaemic patients was 96.6%. Lacunar syndromes due to non ischaemic causes are not rare; since CT scan allowed appropriate treatment in two patients and demonstrated contraindications to antithrombotic therapy in five others, its early use appears warranted in patients with acute lacunar syndromes, particularly if normotensive. .A Anzalone N; Landi G. .I 201708 .U 90011097 .S J Neurol Neurosurg Psychiatry 9001; 52(10):1191-3 .M Adult; Aneurysm, Dissecting/CO/*DI; Case Report; Cerebral Hemorrhage/DI/ET; Human; Infarction/*DI/ET; Magnetic Resonance Imaging; Male; Pons/*BS; Quadriplegia/ET; Vertebral Artery/*/PA. .T Post traumatic extracranial vertebral artery dissection with locked-in syndrome: a case with MRI documentation and unusually favourable outcome. .P JOURNAL ARTICLE. .W A patient with a right vertebral artery dissection occurring after minor head trauma progressed to a massive pontine infarction. An unusually favourable outcome and MRI imaging are discussed. .A Rae-Grant AD; Lin F; Yaeger BA; Barbour P; Levitt LP; Castaldo JE; Lester MC. .I 201709 .U 90011098 .S J Neurol Neurosurg Psychiatry 9001; 52(10):1194-6 .M Histocompatibility Antigens Class I/*BL/CF; Human; Meningitis/*BL/CF; Support, Non-U.S. Gov't; Varicella-Zoster Virus/*. .T Soluble class I antigens in serum and CSF of patients with varicella-zoster virus meningitis. .P JOURNAL ARTICLE. .W Soluble class I antigens (sHLA) are secreted by lymphocytes upon activation in vitro. The intrathecal synthesis (ITS) of these molecules has been studied in patients with the varicella-zoster virus (VZV) meningitis. In this paper we describe a sHLA index IH = (CSF sHLA/serum sHLA): (CSF albumin/serum albumin) which is expected to increase only when sHLA is synthesised within the central nervous system (CNS). The IH is elevated in the first week of meningitis, when antibody synthesis is still low, and decreases thereafter. We think IH is an index of early lymphocyte activation within the CNS. The relation of these findings with previous in vitro studies is also discussed. .A Alvarez-Cermeno J; Echevarria JM; Villar LM; Lazaro I; Bootello A; Gonzalez-Porque P. .I 201710 .U 90011099 .S J Neurol Neurosurg Psychiatry 9001; 52(10):1197-9 .M Adult; Cerebral Aneurysm/CO; Female; Human; HLA Antigens/*AN; HLA-A Antigens/AN; HLA-B Antigens/AN; HLA-D Antigens/AN; Male; Middle Age; Nervous System Diseases/ET/*IM; Rupture, Spontaneous; Subarachnoid Hemorrhage/CO/*IM. .T Are HLA antigens implicated in the pathogenesis of non-haemorrhagic deterioration following aneurysmal subarachnoid haemorrhage. .P JOURNAL ARTICLE. .W Aneursymal subarachnoid haemorrhage is frequently complicated by non-haemorrhagic deterioration. HLA typing was studied in a group of 40 patients who had sustained an aneurysmal subarachnoid haemorrhage in order to assess its ability to identify those who are likely to experience non-haemorrhagic deterioration. The antigen HLA-B7 appeared to be associated with an increased likelihood of this event supervening. Conversely, the antigen HLA-DR3, seemed to exert a "protective" influence. .A Lye RH; Dyer PA; Sheldon S; Antoun N. .I 201711 .U 90011100 .S J Neurol Neurosurg Psychiatry 9001; 52(10):1200-1 .M Brain Injuries/*CO; Bromocriptine/*TU; Case Report; Human; Male; Middle Age; Psychomotor Agitation/*DT/ET. .T Akathisia following traumatic brain injury: treatment with bromocriptine [letter] .P LETTER. .A Stewart JT. .I 201712 .U 90011101 .S J Neurol Neurosurg Psychiatry 9001; 52(10):1201-2 .M Adult; Cartilage; Case Report; Embolism/ET/*PA; Human; Male; Spinal Cord/*BS; Spinal Cord Diseases/ET/*PA. .T Cartilage embolism of spinal cord [letter] .P LETTER. .A Banerjee AK; Deodhar SD. .I 201713 .U 90011102 .S J Neurol Neurosurg Psychiatry 9001; 52(10):1202-3 .M Adult; Basilar Artery/PA; Brain Neoplasms/*CO/RA; Case Report; Female; Human; Meningioma/*CO/RA; Trigeminal Neuralgia/*ET/RA. .T Trigeminal neuralgia associated with contralateral intracranial tumour: a false localising sign caused by vascular compression? Report of two cases [letter] .P LETTER. .A Michelucci R; Tassinari CA; Plasmati R; Rubboli G; Forti A; Tognetti F; Calbucci F. .I 201714 .U 90011103 .S J Neurol Neurosurg Psychiatry 9001; 52(10):1212 .M Behcet's Syndrome/*DI; Human; Magnetic Resonance Imaging. .T MRI in Behcet's disease [letter; comment] .P COMMENT; LETTER. .A Kermode AG. .I 201715 .U 90011105 .S J Neurol Neurosurg Psychiatry 9001; 52(10):1213 .M Chronic Disease; Headache/*BL; Human; Serotonin/*BL. .T Plasma serotonin in patients with chronic tension headaches [letter; comment] .P COMMENT; LETTER. .A Chaturvedi SK. .I 201716 .U 90011106 .S J Neurol Neurosurg Psychiatry 9001; 52(10):1213 .M Adult; Arm; Case Report; Female; Hand; Human; Male; Neck/*IN; Tremor/*ET; Wrist Injuries/*CO. .T Two other cases of unilateral essential tremor, induced by peripheral trauma [letter] .P LETTER. .A Herbaut AG; Soeur M. .I 201717 .U 90011107 .S J Neurol Neurosurg Psychiatry 9001; 52(8):1002-5 .M Adult; Antibody Specificity; Biopsy; Borrelia/IM; Case Report; Female; Human; IgG/AN; Lyme Disease/DI/IM/*PA; Muscles/PA; Myositis/*PA; Necrosis. .T Myositis during Borrelia burgdorferi infection (Lyme disease). .P JOURNAL ARTICLE. .W During the second stage of an illness caused by Borrelia burgdorferi, a young woman developed a myopathic syndrome characterised by severe muscular pains, incapacitating weakness of the proximal limb and the neck, as well as the bulbar muscles and elevated serum CK levels. Muscle biopsy revealed a non-inflammatory necrotising myopathy. B. burgdorferi infection was confirmed by a considerable rise of specific IgG antibodies. A course of high dose steroids alleviated the myalgias, but paresis began to improve only after treatment with antibiotics. Our observations confirm that B burgdorferi can cause, through an undertermined mechanism, a necrotising myopathy, in addition to the wide spectrum of already known neurological complications. .A Schoenen J; Sianard-Gainko J; Carpentier M; Reznik M. .I 201718 .U 90011108 .S J Neurol Neurosurg Psychiatry 9001; 52(8):1006-9 .M Aged; Brain/*PA; Case Report; Cerebral Ischemia/PA; Chlorpromazine/AD/*AE; Depressive Disorder/*DT; Drug Therapy, Combination; Female; Human; Isocarboxazid/AD/*AE; Muscles/*PA; Neuroleptic Malignant Syndrome/*PA; Subarachnoid Hemorrhage/PA. .T Neuroleptic malignant syndrome: a case report with post-mortem brain and muscle pathology [see comments] .P JOURNAL ARTICLE. .W The neuroleptic malignant syndrome is a rare but dangerous complication of treatment with neuroleptics. The aetiology and pathophysiology of the syndrome are reviewed, and a fatal case is presented where both brain and muscle pathology are described. Striking myopathic changes in this case, accompanied by only minimal and non-specific brain abnormalities, support a peripheral rather than central mechanism for the hyperthermia. .A Jones EM; Dawson A. .I 201719 .U 90011109 .S J Neurol Neurosurg Psychiatry 9001; 52(8):1010-1 .M Acquired Immunodeficiency Syndrome/*CO; Adult; Antibodies, Viral/AN; Case Report; Cytomegalic Inclusion Disease/*CO; Cytomegaloviruses/IM; Encephalitis/*CO; Female; Human; HIV Antibodies/AN; HIV-1/*IM; Opportunistic Infections/*CO; Sinus Thrombosis/*CO. .T Cerebral venous thrombosis and dual primary infection with human immunodeficiency virus and cytomegalovirus. .P JOURNAL ARTICLE. .A Meyohas MC; Roullet E; Rouzioux C; Aymard A; Pelosse B; Eliasceiwicz M; Frottier J. .I 201720 .U 90011110 .S J Neurol Neurosurg Psychiatry 9001; 52(8):1011-3 .M Adult; Brain Neoplasms/*PA; Brain Stem/*PA; Case Report; Cerebral Ventricles/PA; Female; Glioma/*PA; Human; Meningeal Neoplasms/*PA; Spinal Cord/PA. .T Supratentorial meningeal spread from brainstem glioma. .P JOURNAL ARTICLE. .A Vries EP; De Visser M; Troost D. .I 201721 .U 90011111 .S J Neurol Neurosurg Psychiatry 9001; 52(8):1013-4 .M Adult; Case Report; Dystonia Musculorum Deformans/ET/*IM; Follow-Up Studies; Human; IgG/*CF; Immunoglobulins/*CF; Male. .T CSF oligoclonal IgG bands in a patient with torsion dystonia [letter] .P LETTER. .A Wroe SJ; Gills PD; Cull RE. .I 201722 .U 90011112 .S J Neurol Neurosurg Psychiatry 9001; 52(8):1014-5 .M Case Report; Human; Male; Middle Age; Synovial Cyst/*CO/SU; Tarsal Tunnel Syndrome/*CO/SU; Tibial Nerve/*/SU. .T Tarsal tunnel syndrome secondary to intraneural ganglion [letter] .P LETTER. .A Poppi M; Giuliani G; Pozzati E; Acciarri N; Forti A. .I 201723 .U 90011113 .S J Neurol Neurosurg Psychiatry 9001; 52(8):1015-6 .M Adolescence; Adult; Aged; Alzheimer's Disease/UR; Biopterin/*AA/*UR; Child; Child, Preschool; Down's Syndrome/*UR; Female; Human; Infant; Male; Middle Age. .T Neopterin: biopterin ratios in Down's syndrome [letter] .P LETTER. .A Cattell RJ; Hamon CG; Corbett JA; Lejeune J; Blair JA. .I 201724 .U 90011114 .S J Neurol Neurosurg Psychiatry 9001; 52(8):1016-7 .M Atrophy; Human; Laminectomy/*; Magnetic Resonance Imaging/*; Postoperative Complications/*DI; Risk Factors; Spinal Cord/*PA; Spinal Cord Compression/*DI; Spinal Osteophytosis/*SU. .T Magnetic resonance imaging in patients with progressive myelopathy following spinal surgery [letter; comment] [see comments] .P COMMENT; LETTER. .A Adams CB. .I 201725 .U 90011115 .S J Neurol Neurosurg Psychiatry 9001; 52(8):1017 .M Cross-Sectional Studies; Human; Life Expectancy; Multiple Sclerosis/*EP/MO; Wales. .T The prevalence of multiple sclerosis in south east Wales [letter; comment] .P COMMENT; LETTER. .A Martyn CN; Osmond C. .I 201726 .U 90011116 .S J Neurol Neurosurg Psychiatry 9001; 52(8):1017-8 .M Adult; Anemia, Pernicious/*PP; Case Report; Evoked Potentials, Somatosensory/*; Follow-Up Studies; Human; Male; Neural Transmission/*; Peripheral Nerves/*PP; Spinal Cord/PP. .T Delayed somatosensory evoked potentials in pernicious anaemia with intact peripheral nerves [letter] .P LETTER. .A Perkin GD; Roche SW; Abraham R. .I 201727 .U 90011117 .S J Neurol Neurosurg Psychiatry 9001; 52(8):1018-9 .M Elasticity; Elbow/PP; Electromyography; Human; Muscle Contraction/*; Muscle Spasticity/*PP; Muscle Tonus/*; Muscles/*PP. .T Elastic properties of muscle measured at the elbow in man. Defining velocity sensitive resistance to passive movement in a clinically measurable manner [letter] .P LETTER. .A Carter CL. .I 201728 .U 90011119 .S J Neurol Neurosurg Psychiatry 9001; 52(8):1020-1 .M Adult; Autoimmune Diseases/*CO; Blindness/*ET; Cerebrovascular Disorders/*CO; Deafness/*ET; Female; Human; Organic Mental Disorders/*ET; Retinal Artery Occlusion/*ET. .T Encephalopathy, deafness and blindness in young women: a distinct retinocochleocerebral arteriolopathy? [letter; comment] .P COMMENT; LETTER. .A Asherson RA; Gledhill R. .I 201729 .U 90011121 .S J Neurol Neurosurg Psychiatry 9001; 52(8):940-8 .M Adult; Chronic Disease; Comparative Study; Depressive Disorder/*CO; Diagnosis, Differential; Fatigue/*ET; Fatigue, Mental/ET; Female; Human; Male; Middle Age; Neuromuscular Diseases/*CO; Somatoform Disorders/ET; Virus Diseases/*CO. .T Fatigue syndromes: a comparison of chronic "postviral" fatigue with neuromuscular and affective disorders. .P JOURNAL ARTICLE. .W Patients (n = 47) presenting to a neurological centre with unexplained chronic "postviral" fatigue (CFS) were studied prospectively. Controls were patients with peripheral fatiguing neuromuscular diseases and inpatients with major depression in a psychiatric hospital. Seventy-two percent of the CFS patients were cases of psychiatric disorder, using criteria that excluded fatigue as a symptom, compared with 36% of the neuromuscular group. There was no difference in subjective complaints of physical fatigue between all groups. Mental fatigue and fatigability was equally common in CFS and affective patients, but only occurred in those neuromuscular patients who were also cases of psychiatric disorder. Overall, the CFS patients more closely resembled the affective than the neuromuscular patients. Attribution of symptoms to physical rather than psychological causes was the principal difference between matched CFS and psychiatric controls. The symptoms of "postviral" fatigue had little ability to discriminate between CFS and affective disorder. The fatigue in CFS appeared central in origin, suggesting it is not primarily a neuromuscular illness. The implications for research and treatment of chronic fatigue are discussed. .A Wessely S; Powell R. .I 201730 .U 90011124 .S J Neurol Neurosurg Psychiatry 9001; 52(8):962-6 .M Adult; Aged; Blood Flow Velocity/DE; Cerebral Arteries/DE; Cerebrovascular Circulation/*DE; Dopamine beta-Hydroxylase/DF; Dysautonomia, Familial/*DT/GE; Ephedrine/*TU; Female; Genes, Recessive; Human; Hypotension, Orthostatic/*DT/GE; Male; Middle Age; Vascular Resistance/DE. .T The effect of orthostatic hypotension on cerebral blood flow and middle cerebral artery velocity in autonomic failure, with observations on the action of ephedrine. .P JOURNAL ARTICLE. .W Cerebral blood flow (CBF) and middle cerebral artery velocity (MCAv) have been measured using 133xenon washout and transcranial Doppler in ten patients with autonomic failure. Four pure autonomic failure and four multiple system atrophy patients behaved similarly: tilting them sufficiently to induce significant orthostatic hypotension without causing syncopal symptoms led to a significant fall in their mean MCAv, but no change in their mean CBF. These findings suggest that cerebral autoregulation is preserved in autonomic failure, orthostatic hypotension resulting in a reactive vasodilatation which lowers MCAv, reduces vascular resistance, and maintains CBF. Ephedrine helped to correct the orthostatic hypotension, but had no direct effect on CBF. Two siblings with orthostatic hypotension secondary to dopamine-beta-hydroxylase deficiency also had preserved cerebral autoregulation, but ephedrine led to paradoxical hypotension in these patients. .A Brooks DJ; Redmond S; Mathias CJ; Bannister R; Symon L. .I 201731 .U 90011125 .S J Neurol Neurosurg Psychiatry 9001; 52(8):967-9 .M Adolescence; Adult; Brain/PA; Electrooculography/IS; Eye Movements/*; Female; Human; Magnetic Resonance Imaging/*; Male; Middle Age; Multiple Sclerosis/*DI; Ophthalmoplegia/DI; Saccades/*; Signal Processing, Computer-Assisted. .T Role of saccadic analysis in the diagnosis of multiple sclerosis in the era of magnetic resonance imaging. .P JOURNAL ARTICLE. .W Magnetic resonance imaging (MRI) has recently been recognised as the most sensitive method with which to detect clinically silent lesions in patients affected by multiple sclerosis. Visually guided horizontal saccadic eye movements (SEM) were studied, together with MRI, in 57 multiple sclerosis patients. A very similar sensitivity was found for both MRI (78.2%) and SEM analysis (76.3%). Significant associations between peak saccadic velocity and brain stem signs and between saccadic latency and visual signs were observed. .A Tedeschi G; Allocca S; Di Costanzo A; Diano A; Bonavita V. .I 201732 .U 90011126 .S J Neurol Neurosurg Psychiatry 9001; 52(8):970-4 .M Adult; Aged; Axons/PH; Electric Stimulation; Female; Human; Male; Microcomputers; Middle Age; Motor Cortex/*PP; Muscles/*IR; Neural Transmission/*; Osteoarthritis/PP; Pyramidal Tracts/*PP; Reaction Time/PH; Signal Processing, Computer-Assisted; Spinal Cord Neoplasms/PP. .T Corticospinal potentials after transcranial stimulation in humans. .P JOURNAL ARTICLE. .W The descending volley evoked in humans by transcranial electrical stimulation of the scalp was recorded with epidural and spinal electrodes. It consisted of an early wave, which increased in amplitude and decreased in latency when the strength of the stimulus was increased. The mean conduction velocity of the early wave was 66, SD 2.5 m/s. At high stimulus intensity this wave was followed by later and smaller waves, which travel at the same speed as the initial potential. The recovery cycle of the descending volley was studied by delivering paired cortical stimuli at time intervals ranging from 0.5 to 10 ms. The early wave evoked by the test stimulus recovered to about 50% at a 1 ms interval and to 100% at a 3.5 ms interval. The later waves could not be tested at short time intervals but with time intervals longer than 3.5 ms they recovered to 100%. It is suggested that the initial and later waves after scalp stimulation are equivalent to the D and I waves seen in animal experiments. .A Inghilleri M; Berardelli A; Cruccu G; Priori A; Manfredi M. .I 201733 .U 90011128 .S J Neurol Neurosurg Psychiatry 9001; 52(8):980-5 .M Aged; Aged, 80 and over; Alpha Rhythm; Alzheimer's Disease/PP; Cerebral Cortex/PP; Delirium/DI/*PP; Dementia, Multi-Infarct/PP; Electroencephalography/*IS; Female; Human; Male; Microcomputers/*; Middle Age; Parkinson Disease/PP; Signal Processing, Computer-Assisted/*; Support, Non-U.S. Gov't; Theta Rhythm. .T EEG spectral analysis in delirium. .P JOURNAL ARTICLE. .W Spectral analysis of EEG was conducted for 51 elderly delirious patients meeting the Diagnostic and Statistical Manual of Mental Disorders III (DSM-III) criteria and for 19 controls. As a whole group, and also when subdivided according to the type of delirium, severity of cognitive decline or the type of central nervous system disease, delirious patients showed significant reductions of alpha percentage, increased theta and delta activity and slowing of the peak and mean frequencies and these changes were also obvious in individual recordings. The alpha percentage and various ratio parameters correlated significantly with Mini Mental State score, and delta percentage and mean frequency with the lengths of delirium and hospitalisation. The results indicate an association between spectral EEG changes and severity of cognitive deterioration in delirium. .A Koponen H; Partanen J; Paakkonen A; Mattila E; Riekkinen PJ. .I 201734 .U 90011129 .S J Neurol Neurosurg Psychiatry 9001; 52(8):986-90 .M Adolescence; Adult; Cerebellar Diseases/DI/*SU; Cerebellopontine Angle/SU; Child; Electrocoagulation/MT; Epidermal Cyst/DI/*SU; Female; Human; Male; Microsurgery/MT; Middle Age; Retrospective Studies; Tomography, X-Ray Computed. .T Cerebellopontine angle epidermoid cysts: a report on 30 cases. .P JOURNAL ARTICLE. .W Thirty cases of cerebellopontine angle epidermoid cysts treated over a period of 20 years are reviewed with regard to their clinical features, the pathophysiology of their symptoms and their management. The predominating symptoms were related to the 7th and 8th cranial nerves and headaches. The signs and symptoms were present for an average period of 4 months. It was not always possible to determine if the signs and symptoms were due to local involvement by the epidermoid, increased intracranial pressure, or both. Diagnostic procedures evolved from angiography and ventriculography to non-invasive computed tomography and MRI. The posterior cranial fossa approach was used in 27 cases. Total excision of the epidermoid was the aim and was carried out in five (18%) patients but concern regarding the preservation of nearby important neurovascular structures forced partial removal in 22 patients. To minimise reformation, the residual epidermoid was carefully coagulated with the aid of the operating microscope and bipolar cautery without damaging surrounding neurovascular structures. .A deSouza CE; deSouza R; da Costa S; Sperling N; Yoon TH; Abdelhamid MM; Sharma RR; Goel A. .I 201735 .U 90011131 .S J Neurol Neurosurg Psychiatry 9001; 52(8):996-8 .M Blepharoptosis/ET/*SU; Case Report; Connective Tissue/*SU; Eyelids/*SU; Facial Muscles/SU; Female; Human; Middle Age. .T Recognising aponeurotic ptosis. .P JOURNAL ARTICLE. .W Thirteen patients who had ptosis surgery undertaken for disinsertion of the aponeurosis of the levator palpebrae superioris were reviewed. Pre-operatively all the patients had characteristic clinical signs of levator disinsertion which was confirmed at surgery and corrected by reposition of the disinserted aponeurosis. Five of these patients were initially mistakenly diagnosed as having a neurological cause for their ptosis. The diagnosis of this type of ptosis may easily be missed. .A Deady JP; Morrell AJ; Sutton GA. .I 201736 .U 90011132 .S J Neurol Neurosurg Psychiatry 9001; 52(8):999-1001 .M Adult; Aged; Analgesia, Epidural/*IS; Catheters, Indwelling/*; Combined Modality Therapy; Female; Human; Male; Middle Age; Morphine/*AD; Pain Measurement; Pain, Intractable/*DT; Physical Therapy; Polyradiculoneuritis/*PP. .T Epidural morphine analgesia in Guillain Barre syndrome. .P JOURNAL ARTICLE. .W Severe pain is a frequent symptom in the Guillain Barre syndrome and can be intense, long lasting and with no response to the usual analgesics, including parenteral opiates. Epidural analgesia using morphine chloride in low doses has satisfactorily relieved pain in this disease in nine patients. .A Genis D; Busquets C; Manubens E; Davalos A; Baro J; Oterino A. .I 201737 .U 90011133 .S J Neurol Neurosurg Psychiatry 9001; 52(9):1025-32 .M Action Potentials; Adult; Electric Stimulation; Electromagnetic Fields/*; Electromagnetics/*; Female; Human; Male; Peripheral Nerves/*PH; Spinal Cord/*PH; Support, Non-U.S. Gov't. .T Magnetic stimulation over the spinal enlargements. .P JOURNAL ARTICLE. .W Magnetic stimulation over the cervical and lumbar spinal enlargements was performed in 10 normal volunteers using a 9 cm diameter coil. Although the threshold and the amplitude of responses depended on the position of the coil and the direction of current flow within it, the latency was constant. The latencies obtained by magnetic stimulation were compatible with those obtained using high voltage electrical stimulation of the spinal nerve roots and always were shorter than the peripheral motor conduction time estimated by F-wave techniques. The site of activation by magnetic stimulation appears to be very similar to that stimulated by the high-voltage electrical method. Stimulation of descending motor tracts within the cord was not possible using the magnetic stimulator. .A Ugawa Y; Rothwell JC; Day BL; Thompson PD; Marsden CD. .I 201738 .U 90011134 .S J Neurol Neurosurg Psychiatry 9001; 52(9):1033-42 .M Aged; Eye Movements/*; Female; Human; Male; Middle Age; Parkinson Disease/*PP; Psychomotor Performance/*PH; Reaction Time/PH; Support, Non-U.S. Gov't. .T Predictive responses in Parkinson's disease: manual keypresses and saccadic eye movements to regular stimulus events. .P JOURNAL ARTICLE. .W In a coincidence timing task, Parkinsonian patients and a control group were instructed to synchronize a keypress with the onset of a visual signal which had been preceded by a regular train of warning signals. Although the Parkinsonian group had previously exhibited slower reactions in a conventional simple reaction-time task, they were able to generate predictive responses that fell as close to the target onset as the controls' but showed greater variability. In a second experiment, Parkinsonian patients and controls made saccadic eye movements to a visual target that stepped at regular intervals between two fixed locations. After a few trials all the subjects tended to make predictive saccades that were initiated before the target excursion. However, the Parkinsonian group were slower to develop this strategy and when they did their saccades became considerably more hypometric than those of the controls. Both groups were able to maintain predictive responding even when the visual target disappeared and responses were paced by a buzzer. We concluded that Parkinsonian patients are capable of initiating predictive responses of the eye and the hand, at least in some circumstances, but such responses tend to be inaccurate in execution. This, in turn, may dispose the Parkinsonian patient against predictive movement. .A Crawford T; Goodrich S; Henderson L; Kennard C. .I 201739 .U 90011135 .S J Neurol Neurosurg Psychiatry 9001; 52(9):1043-9 .M Adolescence; Adult; Aged; Dystonia Musculorum Deformans/*PP; Elbow/*PH; Female; Human; Male; Middle Age; Psychomotor Performance/*; Support, Non-U.S. Gov't. .T Rapid elbow movements in patients with torsion dystonia. .P JOURNAL ARTICLE. .W Rapid, self paced and self terminated elbow flexion movements were studied in a group of 10 patients with dystonia affecting the arms. The movements were slower and for small amplitude movements, more variable than those recorded in normal subjects. The duration of the first agonist burst was prolonged, even when compared with normal subjects deliberately moving slowly. Cocontraction of agonist and antagonist muscles during ballistic movements was common and may contribute to the bradykinesia. These findings are compared with similar studies of other diseases of the motor system. Unlike many other conditions which also reduce the speed of ballistic voluntary movements, the patients with dystonia in the present study showed a normal symmetry of acceleration and deceleration times. One interpretation of this finding is that aspects of the basic motor programmes are relatively preserved in this condition and account for the surprising retention of motor skills shown by some patients with dystonia. .A van der Kamp W; Berardelli A; Rothwell JC; Thompson PD; Day BL; Marsden CD. .I 201740 .U 90011136 .S J Neurol Neurosurg Psychiatry 9001; 52(9):1050-7 .M Action Potentials; Amygdaloid Body/PP/SU; Epilepsy, Temporal Lobe/PA/PP/*SU; Evoked Potentials; Hippocampus/PA/*PP/SU; Human. .T Acute hippocampal recording and pathology at temporal lobe resection and amygdalo-hippocampectomy for epilepsy. .P JOURNAL ARTICLE. .W An electrocorticographic (ECoG) study is reported of patients undergoing surgery for epilepsy of temporal lobe origin. During 22 en bloc resections and six out of a total of 18 amygdalo-hippocampectomies, the activity of the hippocampus was also recorded by a multipolar strip electrode placed along its axis on the ventricular surface. Patients with mesial temporal pathology, chiefly mesial temporal sclerosis, made up the majority of those selected for amygdalo-hippocampectomy. They showed a characteristic ECoG pattern, with spikes localised to the mid part of the second and third convolutions and inferior aspect of the temporal lobe. Typically, this was associated with hippocampal discharges showing an anterior maximum. Pathology involving lateral temporal neocortex and non-specific findings were associated with more widespread temporal spikes and a maximum discharge amplitude over the mid and posterior parts of the hippocampus. It is suggested that intraoperative recording of the ECoG and hippocampal activity may provide a guide to the choice between en bloc resection and amygdalo-hippocampectomy. .A Polkey CE; Binnie CD; Janota I. .I 201741 .U 90011137 .S J Neurol Neurosurg Psychiatry 9001; 52(9):1058-62 .M Adolescence; Adult; Aged; Chorda Tympani Nerve/PH/*SU; Human; Laterality/PH; Middle Age; Salivation/*; Sialorrhea/PP/*SU; Taste/*PH. .T The effect of chorda tympani section on ipsilateral and contralateral salivary secretion and taste in man. .P JOURNAL ARTICLE. .W Bilateral chorda tympani section is an accepted treatment for troublesome sialorrhoea. Nevertheless the effects of this operation have been poorly studied. Twenty patients were studied with unilateral chorda tympani section and a healthy contralateral ear. The effects on ipsilateral and contralateral stimulated submandibular and parotid flow and taste recognition and detection thresholds were measured. Stimulated submandibular flow accounted for only 27% of the total salivary flow. Chorda tympani section had no effect on submandibular flow in seven patients and only reduced submandibular flow by approximately 54% in the remaining 13 patients. No significant effect was observed on ipsilateral parotid flow rate. Electrogustometric taste detection thresholds were more than twice the accepted upper limit of normal on the lesioned side and taste recognition thresholds were also markedly abnormal. Chorda tympani section alone is a poor method of reducing stimulated salivary flow. .A Grant R; Miller S; Simpson D; Lamey PJ; Bone I. .I 201742 .U 90011138 .S J Neurol Neurosurg Psychiatry 9001; 52(9):1063-7 .M Aged; Dietary Proteins/*ME; Female; Human; Levodopa/AD/*PK/TU; Male; Middle Age; Movement Disorders/DT/ET/*PP; Parkinson Disease, Symptomatic/*DT/ME/PP; Support, Non-U.S. Gov't. .T The effects of oral protein on the absorption of intraduodenal levodopa and motor performance. .P JOURNAL ARTICLE. .W Four patients with levodopa induced fluctuations in motor performance were studied during the constant intraduodenal infusion of levodopa. The results confirm that steady plasma levodopa levels with stable motor control can be achieved. However, when patients were given oral protein loads, motor performance declined despite maintenance of plasma levodopa levels. These findings suggest that competition for levodopa carrier mediated transport by amino acids, is more important at the blood-brain barrier than across the gut mucosa; thereby possibly limiting the efficacy of long-term direct intraduodenal administration of levodopa. .A Frankel JP; Kempster PA; Bovingdon M; Webster R; Lees AJ; Stern GM. .I 201743 .U 90011140 .S J Neurol Neurosurg Psychiatry 9001; 52(9):1072-7 .M Adolescence; Adult; Aged; Diabetic Neuropathies/*PP; Female; Human; Male; Middle Age; Monitoring, Physiologic/*MT; Sensory Thresholds/*; Thermoreceptors/*PH. .T A comparison of two methods for measuring thermal thresholds in diabetic neuropathy [see comments] .P JOURNAL ARTICLE. .W Thermal thresholds can be measured psychophysically using either the method of limits or a forced-choice method. We have compared the two methods in 367 diabetic patients, 128 with symptomatic neuropathy. The Sensortek method was chosen for the forced-choice device, the Somedic modification of the Marstock method for a method of limits. Cooling and heat pain thresholds were also measured using the Marstock method. Somedic thermal thresholds increase with age in normal subjects, but not to a clinically significant degree. In diabetics Marstock warm threshold increased by 0.8 degrees C/decade, Sensortek by 0.1 degrees C/decade. Both methods had a high coefficient of variation in normal subjects (Sensortek 29%, Marstock warm 14%, cool 42%). The prevalence of abnormal thresholds was similar for both methods (28-32%), though Marstock heat pain thresholds were less frequently abnormal (18%). Only 15-18% of patients had abnormal results in both tests. Sensortek thresholds were significantly lower on repeat testing, and all thresholds were higher in symptomatic patients. Both methods are suitable for clinical thermal testing, though the method of limits is quicker. In screening studies the choice of a suitable apparatus need not be determined by the psychophysical basis of the test. .A Levy D; Abraham R; Reid G. .I 201744 .U 90011141 .S J Neurol Neurosurg Psychiatry 9001; 52(9):1078-84 .M Myelography/*EC; Prospective Studies; Support, Non-U.S. Gov't. .T A prospective audit of the use and costs of myelography in a regional neuroscience unit. .P JOURNAL ARTICLE. .W A consecutive series of 397 myelograms performed in 385 patients over a six month period at the Mersey Regional Neurosciences Unit is reported. The reasons for performing the myelogram were to identify the cause of a radicular lesion in 54% of patients, a chronic spinal cord lesion in 30%, an acute cord lesion in 9%, suspected disease at the level of the foramen magnum 6%, and for a variety of other conditions in 8%. For the 385 patients undergoing a myelogram in the study period, the median interval from admission to request, request to myelography and from myelography to discharge was nought, one and three days respectively. The proportion of patients submitted to myelography by individual consultants ranged from 7% to 28%. There was a two-fold variation in the delays in the time to requesting and performing myelograms. There was room for improvement in the clinical information supplied on the myelography request form. The role of ancillary investigations and their effect on myelography was unclear. Only 16 of the patients with suspected cord disease had visual evoked responses performed before myelography. Five of them had myelography after an abnormal result. The estimated annual direct cost of myelography in the unit was at least 486,000 pounds. Reorganisation might have yielded hypothetical "savings" of between 30,000 pounds (6%) and 155,000 pounds (32%), though in practical terms these "savings" represented resources which might have been freed for use in other higher priority clinical problems within the unit, rather than true reductions in monetary cost. .A Sandercock PA; Roberts MA; Blumhardt LD. .I 201745 .U 90011142 .S J Neurol Neurosurg Psychiatry 9001; 52(9):1085-9 .M Adolescence; Adult; Aged; Child; Female; Human; Interviews; Male; Medical Records; Middle Age; Multiple Sclerosis/EP/*MO; Wales. .T The incidence and mortality of multiple sclerosis in south east Wales. .P JOURNAL ARTICLE. .W The incidence of multiple sclerosis was shown to be 8.2/10(5)/year (definite or probable 5.4 and suspected 2.8/10(5)/year) during a 3 year prospective study carried out in an area of south east Wales which has a high prevalence of the disease (120/10(5). Mortality in affected individuals who were prevalent at the start of the survey was 3.1/10(5)/year; many deaths resulted from direct complications of multiple sclerosis but 38% were due to unrelated causes. The rate at which new cases were identified approximately matched deletions from the register arising from death, outward migration and other causes so that prevalence did not change significantly during the survey (1985-1988). .A Hennessy A; Swingler RJ; Compston DA. .I 201746 .U 90011143 .S J Neurol Neurosurg Psychiatry 9001; 52(9):1090-4 .M Adult; Aged; Anaerobic Threshold/*; Exertion/*; Female; Human; Lactates/BL; Male; Metabolic Diseases/*DI/ME; Middle Age; Mitochondria/ME/*PA. .T Screening for mitochondrial cytopathies: the sub-anaerobic threshold exercise test (SATET). .P JOURNAL ARTICLE. .W A simple test is described for identifying patients with abnormalities of muscle energy metabolism secondary to mitochondrial dysfunction, based on the venous lactate response to exercise at 90% of predicted work rate at the anaerobic threshold. The test was standardised for age, weight and sex of subjects, and was abnormal in all cases of mitochondrial cytopathy tested, with a false positive rate of 7% in a control population. The test was abnormal in two cases of mitochondrial disease in which muscle biopsy was normal or showed only non-specific changes. .A Nashef L; Lane RJ. .I 201747 .U 90011144 .S J Neurol Neurosurg Psychiatry 9001; 52(9):1095-9 .M Adult; Case Report; Cerebral Arteries/*AB; Cerebral Hemorrhage/*CO/DI; Cerebrovascular Disorders/*ET; Diagnosis, Differential; Female; Human; Magnetic Resonance Imaging; Optic Chiasm/*BS. .T Chiasmal apoplexy: haemorrhage from a cavernous malformation in the optic chiasm. .P JOURNAL ARTICLE. .W We present a patient who experienced sudden onset of orbital headache, visual loss and bitemporal visual field defect. MRI of the optic chiasm suggested a diagnosis of haemorrhage and hence a vascular malformation. Pterional craniotomy revealed an intrachiasmatic haematoma with a cavernous angioma. The malformation was totally excised and vision improved after surgery. The syndrome of chiasmal apoplexy is discussed. .A Regli L; de Tribolet N; Regli F; Bogousslavsky J. .I 201748 .U 90011145 .S J Neurol Neurosurg Psychiatry 9001; 52(9):1100-2 .M Case Report; Child; Encephalomyelitis/*RA; Female; Human; Recurrence; Tomography, X-Ray Computed/*. .T Serial cerebral CT abnormalities in relapsing acute disseminated encephalomyelitis. .P JOURNAL ARTICLE. .W A 7 year old girl developed acute disseminated encephalomyelitis following a Mycoplasma pneumoniae respiratory infection. The illness followed a relapsing course during the first two months. Computed tomography (CT) showed cerebral lesions of a severity and extent out of proportion to the clinical manifestations. The CT abnormalities altered with changes in her clinical state. .A Walker RW; Gawler J. .I 201749 .U 90011146 .S J Neurol Neurosurg Psychiatry 9001; 52(9):1103-6 .M Adult; Case Report; Diagnosis, Differential; Hexosaminidases/ME; Human; Male; Nervous System Diseases/*DI; Sandhoff Disease/*DI/PA/PP; Support, Non-U.S. Gov't. .T Sandhoff disease mimicking adult-onset bulbospinal neuronopathy. .P JOURNAL ARTICLE. .W A 32 year old male is described with an onset of upper limb postural tremor in adolescence followed by muscle cramps. Progressive proximal amyotrophy and weakness in the limbs developed late in the third decade. Examination disclosed, in addition, bilateral facial weakness and mild dysarthria. Enzyme studies revealed hexosaminidase A and B deficiency, indicating a diagnosis of Sandhoff disease. Intra-axonal membranocytoplasmic bodies were present in a rectal biopsy. The presentation, which resembled that of X-linked bulbospinal neuronopathy, widens the clinical spectrum for disorders related to G(M2) gangliosidosis. .A Thomas PK; Young E; King RH. .I 201750 .U 90011147 .S J Neurol Neurosurg Psychiatry 9001; 52(9):1107-9 .M Adult; Evoked Potentials, Visual/*; Female; Human; Hyperventilation/*PP; Male; Middle Age. .T Value of hyperventilation in pattern-reversal visual evoked potentials. .P JOURNAL ARTICLE. .W The effects of a standard 3 minutes' hyperventilation on the full-field pattern-reversal visual evoked potential (VEP) were studied in 33 normal subjects, 30 definite multiple sclerosis patients and in twenty-five patients with abnormal VEPs due to either tumourous compression of the anterior visual pathways or optic atrophy of other origin. Significantly greater reductions in P100 latency occurred in multiple sclerosis patients in comparison with controls (p less than 0.05). This change appeared to be specific for demyelinative type of lesion, for it was not found in cases with other types of pathology. Hyperventilation also increased the sensitivity of visual pathway impairment detection in multiple sclerosis. .A Bednarik J; Novotny O. .I 201751 .U 90011148 .S J Neurol Neurosurg Psychiatry 9001; 52(9):1110-2 .M Adult; Baclofen/AD/*TU; H-Reflex/*DE; Human; Injections, Spinal; Male; Muscle Spasticity/*DT/ET; Reflex, Monosynaptic; Spinal Cord Injuries/CO/*PP. .T Intrathecal baclofen and the H-reflex. .P JOURNAL ARTICLE. .W Baclofen was given intrathecally to six patients with severe lower limb spasticity due to traumatic spinal cord injury. The effects of the drug on spasticity and the ratio between the maximum amplitude of the H reflex and the M response from the soleus (Hmax/Mmax ratio) were assessed. In each patient, spasticity was reduced following intrathecal baclofen and in four patients there was a reduction in the amplitude of the H reflex and Hmax/Mmax ratio. These results suggest that the Hmax/Mmax ratio may be helpful in establishing optimum drug dosage, particularly when the drug is used on a chronic basis. .A Macdonell RA; Talalla A; Swash M; Grundy D. .I 201752 .U 90011149 .S J Neurol Neurosurg Psychiatry 9001; 52(9):1113 .M Adult; Case Report; Chiropractic; Human; Intervertebral Disk Displacement/*ET/SU; Male; Manipulation, Orthopedic/*AE. .T Intradural herniated cervical disc associated with chiropractic spinal manipulation [letter] .P LETTER. .A Destee A; Lesoin F; Di Paola F; Warot P. .I 201753 .U 90011150 .S J Neurol Neurosurg Psychiatry 9001; 52(9):1113-5 .M Adult; Human; Immobilization/*; Male; Sciatica/*ET/PA; Substance Abuse/*. .T Sciatic nerve damage due to toilet seat entrapment: another Saturday night palsy [letter] .P LETTER. .A Tyrrell PJ; Feher MD; Rossor MN. .I 201754 .U 90011151 .S J Neurol Neurosurg Psychiatry 9001; 52(9):1115 .M Adult; Case Report; Female; Human; Schizophrenia/*CI; Torticollis/DT; Trihexyphenidyl/*AE. .T Schizophrenic psychosis associated with benzhexol (artane) therapy [letter] .P LETTER. .A Trend P; Trimble M; Wessely S. .I 201755 .U 90011152 .S J Neurol Neurosurg Psychiatry 9001; 52(9):1116 .M Anticonvulsants/*AE/TU; Case Report; Epilepsy, Temporal Lobe/*DT; Female; Human; Middle Age; Phenytoin/*AE/TU; Primidone/*AE/TU. .T The toxic effects of anticonvulsant drugs in long-term treatment of epilepsy [letter] .P LETTER. .A Ramana R; Silverstone PH; Lishman WA. .I 201756 .U 90011164 .S J Neuropathol Exp Neurol 9001; 48(6):606-9 .M Alzheimer's Disease/*PA; Brain/*PA; Human; Questionnaires; Stains and Staining; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Neuropathological diagnosis of Alzheimer disease [see comments] .P JOURNAL ARTICLE. .A Wisniewski HM; Robe A; Zigman W; Silverman W. .I 201757 .U 90011168 .S J Neuropathol Exp Neurol 9001; 48(6):645-52 .M Brain/*MI; Brain Stem/*MI/PA; Cytomegaloviruses/GE; DNA Probes; DNA, Viral/*AN; Encephalitis/*MI/PA; Herpesvirus hominis/*GE; Human; Neuroglia/*MI/PA; Nucleic Acid Hybridization; Retrospective Studies; Support, Non-U.S. Gov't. .T Herpes simplex virus (HSV) DNA in microglial nodular brainstem encephalitis. .P JOURNAL ARTICLE. .W Thirty-four brains with microglial nodular brain stem encephalitis were retrospectively investigated for herpes simplex virus (HSV) and cytomegalovirus (CMV) by in situ hybridization (ISH) with biotinylated cDNA probes, and by immunocytochemistry with polyclonal and monoclonal antibodies on formalin fixed paraffin embedded serial tissue sections. In 16 cases (47%), HSV DNA was found by ISH in the nuclei of neurons in microglial nodules or in the adjacent parenchyma of the brainstem, and more rarely at various cerebellar and telencephalic sites. None of the 34 cases was labeled for CMV DNA and none revealed HSV or CMV antigens. Ten control brains without microglial nodules were not labeled. This study suggests an HSV etiology for many cases with microglial nodular brainstem encephalitis. .A Schmidbauer M; Budka H; Ambros P. .I 201758 .U 90011169 .S J Neuropathol Exp Neurol 9001; 48(6):653-68 .M Acrylamides/AD/*PD; Animal; Axons/DE/*UL; Axoplasmic Flow/DE; Male; Microscopy, Electron; Microtubules/DE/UL; Nerve Degeneration/*DE; Nitriles/AD/*PD; Rats; Rats, Inbred Strains; Sciatic Nerve/*UL; Support, U.S. Gov't, P.H.S.. .T Axonal degeneration and axonal caliber alterations following combined beta,beta'-iminodipropionitrile (IDPN) and acrylamide administration. .P JOURNAL ARTICLE. .W A new model of neurofilamentous axonal abnormality is described which employs combined administration of beta,beta'-iminodipropionitrile (IDPN) and acrylamide (AC). The model was developed to test the hypothesis that IDPN-induced swelling increases the vulnerability of the distal axon to a second neurotoxic chemical insult. Rats were given a single intraperitoneal (IP) injection of IDPN (1.5 g/kg) one week before receiving a single injection of AC (75 mg/kg, IP). Axonal degeneration was observed at multiple levels along the sciatic nerve at two weeks (with reference to IDPN administration), and was not progressive up to five weeks. Quantitation of degenerating fibers demonstrated that the extent of degeneration increased distally along the sciatic nerve. Single administration of either IDPN or AC did not produce degeneration. Thus, IDPN-induced neurofilamentous swellings alter the susceptibility of the axon to AC neurotoxicity. Two variations of this model were also studied. First, rats given five daily injections of AC (30 mg/kg, IP) beginning one week following IDPN administration developed accumulations of fast axonally transported materials in IDPN-induced microtubule channels. Second, rats given chronic injections of AC (30 mg/kg, IP, five days/week, for four weeks), to reduce the delivery of neurofilaments to the proximal axon, developed less prominent axonal enlargements when challenged with IDPN. Thus, axonal atrophy can mask the development of neurofilamentous axonal swellings. .A Gold BG; Halleck MM. .I 201759 .U 90011170 .S J Neuropathol Exp Neurol 9001; 48(6):669-73 .M Adult; Aged; Amyotrophic Lateral Sclerosis/*ME; Histocytochemistry; Human; Medulla Oblongata/*AN; Middle Age; Neurons/*AN; RNA/*AN. .T Neuronal RNA in nucleus ambiguus and nucleus hypoglossus of patients with amyotrophic lateral sclerosis. .P JOURNAL ARTICLE. .W To establish objectively the involvement of neurons in the medulla oblongata in patients with amyotrophic lateral sclerosis (ALS), ribonucleic acid (RNA) content was determined in neurons of the hypoglossal nucleus and the nucleus ambiguus. Neurons from those two nuclei showed a significant loss of RNA content in patients with ALS; only 57% and 38% of the normal RNA content was found in hypoglossal and ambiguus neurons, respectively. This marked loss of neuronal RNA suggests changes in functional states of neurons, which may contribute to fasciculations in the tongue and difficulties in swallowing often associated with ALS. .A Hartmann HA; McMahon S; Sun DY; Abbs JH; Uemura E. .I 201760 .U 90011174 .S J Neurol 9001; 236(6):315-8 .M Adolescence; Adult; Aged; Central Nervous System Diseases/*EP; Child; Female; Human; Male; Middle Age; Pilot Projects; Questionnaires; Sicily; Support, Non-U.S. Gov't. .T Prevalence survey of major neurological disorders in Sicily. Results of a pilot study. .P JOURNAL ARTICLE. .W A pilot study on the prevalence of neurological disorders in Sicily was carried out with a protocol never previously used in Italy. A screening questionnaire was administered to 1,601 subjects of a community, designed to identify patients with cerebrovascular diseases, epilepsy, extrapyramidal syndromes, peripheral neuropathies, migraine and intracranial neoplasms. Of 262 subjects who were identified as likely to be suffering from neurological illness, 248 (94.6%) were examined by a neurologist. Of these, 8.9% were found to be normal, 46.8% were suffering from non-neurological diseases, 44.3% had one or more neurological diseases (prevalence of 6.8%). This pilot study proved to be a good starting-point for a future major survey. .A Vita G; Morgante L; Grigoletto F; Santoro M; Toscano A; Coraci MA; Meneghini F; Venuto C; Fazio C; Troilo G; et al. .I 201761 .U 90011175 .S J Neurol 9001; 236(6):319-21 .M Age Factors; Child; Child, Preschool; Dystonia/*DI; Female; Human; Infant; Male; Prognosis; Support, Non-U.S. Gov't. .T Idiopathic dystonia with onset in childhood. .P JOURNAL ARTICLE. .W The natural history of early-onset idiopathic dystonia was studied in 30 patients. Worsening of motor symptoms was observed in the early stages, followed by spontaneous stabilization. Most of the patients retained functional independence. None showed mental deterioration, mood alteration or personality disturbance. .A Angelini L; Nardocci N; Rumi V; Lamperti E. .I 201762 .U 90011176 .S J Neurol 9001; 236(6):322-8 .M Adolescence; Adult; Aged; Borrelia Infections/*/CF/DT; Encephalomyelitis/CF/DT/*ET; Enzyme-Linked Immunosorbent Assay; Facial Paralysis/CO; Female; Follow-Up Studies; Human; Male; Meningitis/CF/DT/*ET; Middle Age; Penicillins/TU; Radiculitis/CF/DT/*ET; Tick Infestations. .T Meningoradiculitis and encephalomyelitis due to Borrelia burgdorferi: a follow-up study of 72 patients over 27 years. .P JOURNAL ARTICLE. .W In 1987, follow-up studies were conducted on 72 patients who had had meningoradiculitis and encephalomyelitis (8 patients) due to Borrelia burgdorferi 5-27 years previously. These patients had not been treated with antibiotics, either during the acute disease or during the interval prior to follow-up studies. The patients had exhibited the typical symptoms of Bannwarth's syndrome during the acute phase. At the follow-up studies, 33 patients showed no, and 23 only mild, clinical residual symptoms including normal CSF findings and low-positive serum IgG borrelia antibody titres (IFT; ELISA). Three patients without sequelae exhibited persistent intrathecal secretion of oligoclonal B. burgdorferi-specific CSF IgG antibodies (Immunoblot; positive borrelia CSF IgG antibody titres). Thirteen patients exhibited mild-to-medium sequelae with persistent intrathecal formation of oligoclonal B. burgdorferi-specific CSF IgG antibodies, up to 21 years after the acute illness. This persistence can be interpreted as an "immunological scar syndrome". Our follow-up studies appear to indicate that neurological manifestations of B. burgdorferi infections are generally (with few exceptions) of a benign nature. Most patients can be classified as having been cured without antibiotic therapy. No late manifestations of chronic progressive CNS borreliosis comparable to that of neurosyphilis have been seen following acute untreated neuroborreliosis. .A Kruger H; Reuss K; Pulz M; Rohrbach E; Pflughaupt KW; Martin R; Mertens HG. .I 201763 .U 90011177 .S J Neurol 9001; 236(6):329-35 .M Adult; Aged; Antigens, Surface; Female; Human; Male; Middle Age; Myasthenia Gravis/*IM; Prognosis; Prospective Studies; Receptors, Cholinergic/IM; Support, Non-U.S. Gov't; Suppressor Cells/*IM; Thymectomy; Thymoma/SU; Thymus Neoplasms/SU; Time Factors; T4 Lymphocytes/*IM. .T Circulating CD4+CD8+ cells in myasthenia gravis: supplementary immunological parameter for long-term prognosis. .P JOURNAL ARTICLE. .W Twenty patients with myasthenia gravis (MG) were studied prospectively for up to 5 years after thymectomy, in order to clarify the relationships between disease severity, anti-acetylcholine receptor antibody (anti-AChR) titres, proportions of circulating CD4+CD8+ cells (CD4+CD8+ cell level) and major lymphocyte subsets. The CD4+CD8+ cell levels were closely related to the clinical change within 1 year after surgery in 8 patients who showed a preoperative elevation in the cell levels. This group of patients consisted of six thymomatous and two non-thymomatous patients; the latter were both negative for anti-AChR. The anti-AChR titres generally changed in parallel with the clinical state in 9 of the 16 patients who were followed up for more than a year after thymectomy, and the CD4+CD8+ cell levels were useful in predicting the clinical course in 6 of the above 9 patients and 3 other patients, including antibody-negative cases. The present study suggests that the CD4+CD8+ cell levels may serve as an indicator for long-term prognosis of MG. .A Matsui M; Fukuyama H; Akiguchi I; Kameyama M. .I 201764 .U 90011178 .S J Neurol 9001; 236(6):336-9 .M Adolescence; Adult; Cerebrospinal Fluid/CY; Child; Encephalitogenic Basic Proteins/*CF; Female; Human; Male; Middle Age; Multiple Sclerosis/CF/*IM; Nervous System Diseases/CF/IM; Suppressor Cells/IM; T-Lymphocytes/*IM; T4 Lymphocytes/IM. .T CSF T-cell subsets in multiple sclerosis: relationship to cerebrospinal fluid myelin basic protein and clinical activity [see comments] .P JOURNAL ARTICLE. .W Cerebrospinal fluid myelin basic protein and cerebrospinal fluid and peripheral blood T-cell subsets have been studied in patients with multiple sclerosis and other inflammatory and non-inflammatory nervous system diseases. These biological parameters have been correlated with clinical disease activity. No changes in peripheral blood T-cell subsets were seen in multiple sclerosis patients. Low cerebrospinal fluid T8+ cells occurred only in multiple sclerosis, while high cerebrospinal fluid T4+ cells were detected both in clinically active multiple sclerosis and in inflammatory nervous system diseases. A close relationship was found between cerebrospinal fluid T4/T8 ratio and myelin basic protein in relapsing multiple sclerosis patients. .A Salmaggi A; LaMantia L; Milanese C; Bianchi G; Eoli M; Campi A; Nespolo A. .I 201765 .U 90011179 .S J Neurol 9001; 236(6):340-2 .M Aged; Cerebellum/*BS; Cerebral Angiography/*; Cerebral Ischemia; Cerebrovascular Disorders/*RA; Female; Human; Male; Middle Age; Support, Non-U.S. Gov't; Time Factors. .T Ischaemic supratentorial stroke: angiographic findings in patients examined in the very early phase. .P JOURNAL ARTICLE. .W Eighty patients were studied by angiography within 6 h of an ischaemic stroke. Angiography was carried out with digital equipment and was usually limited to the vascular territory responsible for the neurological deficits. In 12 of 19 patients with internal carotid occlusion, the contralateral side was also studied. The angiographic abnormalities were classified as extracranial, intracranial, and combined extra and intracranial. The data show a high incidence (66%) of occlusive pathology of intracranial arteries, either isolated or associated with a significant presence of a potential embolic source (85%), and a high incidence of carotid occlusions located at the cervical segment (8 of 19). These observations suggest that most strokes are occlusive in origin. .A Bozzao L; Fantozzi LM; Bastianello S; Bozzao A; Argentino C; Lenzi GL; Fieschi C. .I 201766 .U 90011180 .S J Neurol 9001; 236(6):343-8 .M Adolescence; Adult; Aged; Female; Human; Male; Middle Age; Muscles/*PP; Myasthenia Gravis/*DI/PP; Reflex, Acoustic/*; Stapedius/*PP. .T Decay and recovery of the stapedial reflex by prolonged stimulation in the diagnosis of myasthenia gravis. .P JOURNAL ARTICLE. .W The decay and recovery of stapedial reflex amplitude was investigated in 19 patients with myasthenia gravis and 30 control subjects. In 9 untreated patients the amplitude was reduced to less than 10% of the initial amplitude following continuous stimulation for 120 s, whereas the maximum decay in the control subjects was only 50%. In the group of treated patients the reflex decay showed individual variations. The rate of recovery after prolonged stimulation (5 min) was slower in the patient group, especially within the first 30 s of recovery. With increasing age, the rate of decay rose in the patient group as well as in the control group. The technical parameters necessary for obtaining information of clear diagnostic value are indicated, with which it was shown that the continuous prolonged stimulation of the stapedial muscle is a practical and valid method for the evaluation of patients with myasthenia gravis. .A Bischoff C; Klingelhofer J; Conrad B. .I 201767 .U 90011182 .S J Neurol 9001; 236(6):351-2 .M Adult; Aged; Blotting, Western; Female; Human; HTLV-I/*IM; IgG/CF/*IM; IgM/CF/*IM; Male; Middle Age; Paraparesis, Tropical Spastic/CF/*IM. .T Viral specific IgG and IgM antibodies in the CSF of patients with tropical spastic paraparesis. .P JOURNAL ARTICLE. .W The cerebrospinal fluid (CSF) from seven West Indian migrants to the United Kingdom with tropical spastic paraparesis were studied by antigen immunoblotting for specific anti-HTLV1 oligoclonal IgG and IgM. Eight CSFs from five patients were positive for specific IgG and negative for IgM; three CSFs from two patients were positive for IgM and negative for IgG. No patient had both IgG- and IgM-positive CSF. Those patients with IgM only had disease of the shortest duration. When looking for evidence that neurological damage is caused by HTLV1, both IgM and IgG should be examined. .A McLean BN; Rudge P; Thompson EJ. .I 201768 .U 90011183 .S J Neurol 9001; 236(6):353-5 .M Aged; Antibodies, Monoclonal/*IM; Case Report; Enzyme-Linked Immunosorbent Assay; Gangliosides/*IM; Human; IgM/*IM; Male; Neuropathies, Hereditary Motor and Sensory/*IM. .T Motor neuropathy with activity of monoclonal IgM antibody to GD1a ganglioside. .P JOURNAL ARTICLE. .W A patient with motor neuropathy associated with monoclonal IgM protein is reported. Using enzyme-linked immunosorbent assays, the antibody activity of the monoclonal IgM was shown to be directed against GD1a ganglioside, a new and so far unreported specificity. .A Bollensen E; Schipper HI; Steck AJ. .I 201769 .U 90011184 .S J Neurol 9001; 236(6):356-8 .M Adult; Autopsy; Case Report; Central Nervous System Diseases/*DI; Diagnosis, Differential; Female; Granuloma/*DI; Human; Sarcoidosis/*DI; Tomography, X-Ray Computed. .T Isolated central nervous system granulomatosis resembling sarcoidosis. .P JOURNAL ARTICLE. .W Isolated central nervous system (CNS) granulomatosis resembling sarcoidosis occurred in a 30-year-old woman who had amenorrhea, ataxia, and obstructive hydrocephalus, and a 9-year course of progressive neurological deterioration with recurrent bouts of diabetes insipidus. Lamellar and nodular meningeal hyalinosis resembling amyloid was noted on an initial brain biopsy. At autopsy, the brain had a non-necrotizing granulomatous meningitis and ventriculitis, most prominent at the base of the brain, including the third ventricle and the hypothalamus, but there were no systemic granulomas. .A Lee SC; Spencer J; Rumberg J; Dickson DW. .I 201770 .U 90011185 .S J Neurol 9001; 236(6):359-60 .M Astrocytoma/*DI; Case Report; Cerebellar Neoplasms/*DI; Child; Human; Magnetic Resonance Imaging; Male; Nystagmus/*PP; Support, Non-U.S. Gov't; Tomography, X-Ray Computed. .T Upbeat nystagmus as an early sign of cerebellar astrocytoma. .P JOURNAL ARTICLE. .W A boy with a left-hemispheric cerebellar astrocytoma had upbeat nystagmus exhibiting increasing-velocity slow phases. The nystagmus improved after excision of the tumour. .A Traccis S; Rosati G; Aiello I; Monaco MF; Loffredo P; Puliga MV; Pirastru MI; Agnetti V. .I 201771 .U 90011186 .S J Neurol 9001; 236(6):361-3 .M Acidosis, Lactic/CO; Adult; Brain Diseases/*ME; Cerebellar Ataxia/CO; Cerebral Infarction/CO; Cerebrovascular Disorders/*CO; Deafness/CO; Human; In Vitro; Male; Mitochondria/*ME; Phenotype; Vacuoles/*ME. .T Mitochondrial encephalomyopathy with pilovacuolar inclusion or phenocopy with mitochondrial artefact? .P JOURNAL ARTICLE. .W The case of a 33-year-old man with clinical features of mitochondrial encephalomyopathy is presented. He suffered from recurrent cerebral infarctions, cerebellar ataxia, deafness, retinopathy, weakness, and cardiac and renal disorders. Biochemical and light microscope investigations of skeletal muscle did not show any mitochondrial abnormality. Electron microscopy revealed the presence of a hitherto unreported peculiar "pilovacuolar" inclusion in numerous mitochondria, composed of an electron dense pile or rod within a vacuole, while globular or crystalline inclusions were absent. .A Paulus W; Stevens A; Roggendorf W. .I 201772 .U 90011187 .S J Neurol 9001; 236(6):364-6 .M Alcoholism/*CO/PA; Brain Diseases/*DI/ET/PA; Case Report; Corpus Callosum/*/PA; Demyelinating Diseases/*DI/ET/PA; Human; Magnetic Resonance Imaging; Male; Middle Age; Nutrition Disorders/CO/PA; Syndrome; Tomography, X-Ray Computed. .T Marchiafava-Bignami disease with recovery diagnosed by CT and MRI: demyelination affects several CNS structures. .P JOURNAL ARTICLE. .W Marchiafava-Bignami disease (MBD) is a rare complication of chronic alcoholism. Most reported cases have been diagnosed at autopsy. With CT and, especially, MRI it is possible to diagnose MBD in its early stages. Lesions of CNS structures other than the typical demyelination of the corpus callosum are described ante mortem in a patient with MBD. The more frequent use of CT and MRI in sudden onset encephalopathies of alcoholics could reveal the real incidence of MBD, and the consequent detection of other involved CNS systems might improve our knowledge about the aetiology, pathogenesis, prognosis and therapy of MBD. .A Baron R; Heuser K; Marioth G. .I 201773 .U 90011188 .S J Neurol 9001; 236(6):367-70 .M Behcet's Syndrome/*DI/DT/ME; Brain/*ME; Case Report; Cerebrovascular Circulation/*; Dexamethasone/TU; Female; Hemiplegia/DI/DT/ME; Human; Laterality; Middle Age; Oxygen Consumption; Tomography, Emission-Computed/*. .T Sequential PET studies in neuro-Behcet's syndrome. .P JOURNAL ARTICLE. .W A case of neuro-Behcet's syndrome is presented with sequential positron emission tomography (PET) studies. Regional cerebral blood flow (rCBF) and oxygen consumption (rCMRO2) were decreased in the brain lesion; however, on follow-up studies 3 months after steroid therapy rCBF and rCMRO2 had increased in the lesion, which demonstrated the reversibility of this disease. Such monitored improvement may accurately reflect the early stage of the disease and its response to steroid therapy. .A Mineura K; Sasajima T; Kowada M; Shishido F; Uemura K; Nagata K. .I 201774 .U 90011189 .S J Neurol 9001; 236(6):371-2 .M Acute Disease; Case Report; Cerebral Infarction/*CO; Chorea/*ET; Corpus Striatum/*BS; Human; Hypertension/CO; Magnetic Resonance Imaging; Male; Movement Disorders/ET. .T Acute hemichorea due to infarction in the corona radiata. .P JOURNAL ARTICLE. .W A 66-year-old hypertensive man presented with acute hemichorea. Magnetic resonance imaging disclosed an infarct, confined to the contralateral corona radiata, that interrupted excitatory corticostriate fibres. The movement disorder may have been caused by subcortical lesion without direct involvement of the basal ganglia. .A Barinagarrementeria F; Vega F; DelBrutto OH. .I 201775 .U 90011190 .S J Neurol 9001; 236(6):373-4 .M Adult; Amyotrophic Lateral Sclerosis/IM/*PP; Autoimmune Diseases/IM; Female; Human; Male; Middle Age; Thyroid Function Tests/*; Thyroid Gland/IM/PP. .T Amyotrophic lateral sclerosis and thyroid function [letter] .P LETTER. .A Iwasaki Y; Kinoshita M; Ikeda K; Takamiya K; Shiojima T. .I 201776 .U 90011191 .S J Neurol 9001; 236(6):374 .M Almitrine/*AE; Analeptics/*AE; Human; Peripheral Nerve Diseases/*CI; Weight Loss/*. .T Almitrine-induced peripheral neuropathy and weight loss [letter] .P LETTER. .A Gherardi R; Belec L; Louarn F. .I 201777 .U 90011289 .S J Neurosurg 9001; 71(4):481-6 .M Alzheimer's Disease/*DT/PP/PX; Bethanechol Compounds/*AD/AE/TU; Cerebral Ventricles/*; Double-Blind Method; Human; Infusion Pumps; Infusions, Parenteral; Neuropsychological Tests; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Intracerebroventricular bethanechol chloride infusion in Alzheimer's disease. Results of a collaborative double-blind study. .P JOURNAL ARTICLE. .W The use of intracerebroventricular bethanechol chloride infusion in patients with Alzheimer's disease was first reported in 1984. An initial trial in four patients demonstrated the feasibility of this approach for cholinergic drug delivery to the brain, but objective improvement in cognitive function was not documented. A collaborative placebo-controlled double-blind crossover study has now been carried out in 49 patients with biopsy-documented Alzheimer's disease. The results demonstrate a statistical improvement in Mini-Mental State scores and significantly slower performance on Trails A testing during drug infusion. Other neuropsychological test scores were not similarly affected. The degree of improvement was not sufficient to justify further treatment of Alzheimer's disease patients by intracerebroventricular infusion of bethanechol chloride. The drug delivery system used in the study was well tolerated, with two irreversible complications in more than 50,000 patient days. .A Harbaugh RE; Reeder TM; Senter HJ; Knopman DS; Baskin DS; Pirozzolo F; Chui HC; Shetter AG; Bakay RA; Leblanc R; et al. .I 201778 .U 90011290 .S J Neurosurg 9001; 71(4):487-93 .M Adult; Aged; Analysis of Variance; Astrocytoma/SU; Brain Neoplasms/PA/*SU; Comparative Study; Female; Follow-Up Studies; Glioblastoma Multiforme/SU; Glioma/PA/*SU; Human; Male; Middle Age; Multivariate Analysis; Neurosurgery/MT; Oligodendroglioma/SU; Prognosis; Support, U.S. Gov't, P.H.S.. .T Supratentorial anaplastic gliomas in adults. The prognostic importance of extent of resection and prior low-grade glioma. .P JOURNAL ARTICLE. .W A retrospective analysis is presented of factors affecting the length of survival of 285 consecutive adults with newly diagnosed biopsy-proven supratentorial anaplastic glioma (188 cases of glioblastoma multiforme, 76 of anaplastic astrocytoma, 11 of anaplastic mixed glioma, and 10 of anaplastic oligodendroglioma) treated at a regional cancer center from July, 1982, through December, 1987. The approach to initial therapy included maximum feasible resection and radiotherapy. The median survival time for all patients was 35 weeks. Multivariate analysis demonstrated that age, duration of symptoms, preirradiation performance status, tumor histology, accessibility to resection, extent of resection, radiotherapy, and prior low-grade glioma were significant independent variables influencing survival. The prognostic importance of age, duration of symptoms, performance status, and tumor histology are already recognized, but three "new" findings are reported. First, patients with anaplastic oligodendroglioma had the longest median survival time (278 weeks). Second, corrected for accessibility and all other variables, patients with gross total resection lived longer than those with partial resection, and patients with any degree of resection lived longer than those who underwent only a biopsy procedure. Third, patients with anaplastic glioma in whom there was a prior history of low-grade glioma lived significantly longer after the diagnosis of anaplastic glioma than did patients in whom the anaplastic glioma apparently arose de novo. .A Winger MJ; Macdonald DR; Cairncross JG. .I 201779 .U 90011292 .S J Neurosurg 9001; 71(4):498-502 .M Acute Disease; Brain/*PP; Cerebral Hemorrhage/*PP/SU; Coma; Consciousness/*; Head Injuries/PP; Hematoma/*PP/SU; Hematoma, Epidural/PP; Hematoma, Subdural/PP; Human. .T Brain shift, level of consciousness, and restoration of consciousness in patients with acute intracranial hematoma. .P JOURNAL ARTICLE. .W Recently, Ropper reported that horizontal brain shift caused by acute unilateral mass lesions correlated closely with consciousness, and suggested that recovery of consciousness was unlikely to occur after surgical evacuation if the shift was insufficient to explain the observed diminution of consciousness. The authors have sought to confirm the correlation of pineal shift with level of consciousness and to assess the prognostic value of brain shift measurements in a prospective study. Forty-six patients (19 with subdural hematoma, 14 with intracerebral hematoma, and 13 with epidural hematoma) were accrued to the study group consecutively. A correlation was found between a decrease in the level of consciousness and a significant increase in the mean lateral brain displacement at the pineal gland (from 3.8 to 7.0 mm) and septum (5.4 to 12.2 mm). When outcome was examined in patients who were stuporous or comatose on admission, a significant increase in septal shift was found among patients with a poor outcome, but there was no significant relationship between outcome and degree of pineal or aqueductal shift. A poor outcome was more likely with effacement of both perimesencephalic cisterns or the ipsilateral cistern, but not the contralateral cistern, although this difference did not reach statistical significance. These results do not substantiate the value of brain shift as an independent prognostic factor after evacuation of an acute unilateral mass lesion. The decision to operate and the determination of prognosis should be based rather on established criteria such as the clinical examination, age of the patient, and the mechanism of injury. .A Ross DA; Olsen WL; Ross AM; Andrews BT; Pitts LH. .I 201780 .U 90011293 .S J Neurosurg 9001; 71(4):503-5 .M Brain Neoplasms/PP/*SU; Cerebellar Neoplasms/PP/SC/SU; Hemangiosarcoma/PP/SU; Human; Intracranial Pressure/*; Meningeal Neoplasms/PP/SU; Meningioma/PP/SU; Monitoring, Physiologic; Neuroma, Acoustic/PP/SU. .T Intracranial pressure monitoring in the posterior fossa: a preliminary report [see comments] .P JOURNAL ARTICLE. .W Direct therapeutic drainage and intracranial pressure monitoring from the posterior fossa has never been accepted in neurosurgical practice. Potential complications including cerebrospinal fluid leak, cranial nerve palsies, and brain-stem irritation have been a major deterrent. The authors placed a catheter for pressure monitoring in the posterior fossa of 20 patients in the course of posterior fossa surgery: 14 patients with acoustic schwannomas, four with posterior fossa meningiomas, one with cerebellar hemangioblastoma, and one with a solitary cerebellar metastatic lesion. A Richmond bolt was also placed in the frontal area. Continuous monitoring of the supratentorial and infratentorial compartments was performed for 48 hours. During the first 12 hours the posterior fossa pressure was 50% greater than that of the supratentorial space in all patients (p less than 0.01). Over the next 12 hours the supratentorial pressure was 10% and 15% higher than the posterior fossa pressures in all patients, and by 48 hours of monitoring the pressures had equilibrated. There was no mortality or morbidity referable to insertion of the posterior fossa catheter. The conclusions drawn from this study are that: 1) direct monitoring and drainage of the posterior fossa is safe and effective; and 2) within the early postoperative period, the supratentorial pressures failed to reflect what is taking place within the posterior fossa. The implications and advantages of direct posterior fossa monitoring in the postoperative patient are discussed. .A Rosenwasser RH; Kleiner LI; Krzeminski JP; Buchheit WA. .I 201781 .U 90011294 .S J Neurosurg 9001; 71(4):506-11 .M Adult; Cranial Nerve Neoplasms/PA/*SU; Female; Human; Magnetic Resonance Imaging; Male; Neurilemmoma/PA/*SU; Neurosurgery/*MT; Trigeminal Nerve/*. .T Trigeminal neurinomas: operative approach in eight cases. .P JOURNAL ARTICLE. .W The authors report eight cases of trigeminal neurinoma managed over the past 13 years with radical resection at a single-stage operation. Three patients were male and five were female, ranging in age from 25 to 56 years (mean 41.5 years). One had von Recklinghausen's disease. The tumors were located mainly within the middle fossa in two cases and within the posterior fossa in two, and extended both supra-and infratentorially in four cases. Facial pain and hearing disturbance were the main symptoms, with various other symptoms such as focal seizures, hemiparesis, gait disturbance, increased intracranial pressure, and visual disturbance also being noted. All patients underwent radical tumor resection with either a transpetrosal transtentorial or orbitozygomatic infratemporal surgical approach; the approach depended on the topography of the tumor. Total removal was performed in all cases. Only one patient, treated early in the series, required a second operation to remove the tumor completely. In another case the tumor recurred 5 years after the operation. There has been no operative mortality, but injury or permanent damage to the trigeminal branches was inevitable in many cases. The surgical results were excellent in three patients and good in five. .A Yasui T; Hakuba A; Kim SH; Nishimura S. .I 201782 .U 90011295 .S J Neurosurg 9001; 71(4):512-9 .M Adult; Basilar Artery/RA; Case Report; Cerebral Aneurysm/RA/SU/*TH; Cerebral Angiography; Embolization, Therapeutic/*MT; Female; Human; Male; Middle Age. .T Detachable balloon embolization therapy of posterior circulation intracranial aneurysms [see comments] .P JOURNAL ARTICLE. .W Treatment of complex and surgically difficult intracranial aneurysms of the posterior circulation is now being performed with intravascular detachable balloon embolization techniques. The procedure is carried out under local anesthesia from a transfemoral arterial approach, which allows continuous neurological monitoring. Under fluoroscopic guidance, the balloon is propelled by blood flow through the intracranial circulation and in most cases, can be guided directly into the aneurysm, thus preserving the parent vessel. If an aneurysm neck is not present, test occlusion of the parent vessel is performed and, if tolerated, the balloon is detached. Twenty-six aneurysms in 25 patients have been treated by this technique. The aneurysms have involved the distal vertebral artery (five cases), the mid-basilar artery (six cases), the basilar artery (11 cases), and the posterior cerebral artery (four cases). The aneurysms varied in size and included three small (less than 12 mm), 15 large (12 to 25 mm), and eight giant (greater than 25 mm). Fifteen patients (60%) presented with hemorrhage and 10 patients (40%) with mass effect. In 17 cases (65%) direct balloon embolization of the aneurysm was achieved with preservation of the parent artery. In nine cases (35%), because of aneurysm location and size, occlusion of the parent vessel was performed. Complications from therapy included three cases of transient cerebral ischemia which resolved, three cases of stroke, and five deaths due to immediate or delayed aneurysm rupture. The follow-up period has ranged from 2 months to 43 months (mean 22.5 months). In cases where posterior circulation aneurysms have been difficult to treat by conventional neurosurgical techniques, intravascular detachable balloon embolization may offer an alternative therapeutic option. .A Higashida RT; Halbach VV; Cahan LD; Hieshima GB; Konishi Y. .I 201783 .U 90011296 .S J Neurosurg 9001; 71(4):520-7 .M Adenoma/CO/PA/SE/*SU; Adrenocorticotropic Hormone/SE; Adult; Cushing's Syndrome/ET/*SU; Female; Follow-Up Studies; Human; Male; Middle Age; Neurosurgery/MT; Pituitary Neoplasms/CO/PA/SE/*SU; Sphenoid Bone. .T Repeat transsphenoidal surgery for Cushing's disease. .P JOURNAL ARTICLE. .W Transsphenoidal resection of adrenocorticotrophic hormone (ACTH)-producing pituitary adenomas has the potential of curing most patients with Cushing's disease. However, transsphenoidal exploration of the pituitary is not always curative, and patients who have remission of hypercortisolism following surgery occasionally develop a recurrence. Whether repeat pituitary surgery should be performed for recurrent or persistent Cushing's disease has not been evaluated previously. To determine the efficacy of transsphenoidal surgery in recurrent or persistent Cushing's disease, we performed transsphenoidal surgery in 31 patients (22 women and nine men) who had previously undergone a transsphenoidal operation and two female patients who had had previous pituitary irradiation only. In 24 (73%) of the 33 patients, remission of hypercortisolism was achieved by surgery. Although preoperative computerized tomography (CT) scanning identified an adenoma in only three of the 33 patients, in 20 patients a discrete adenoma was identified at pituitary exploration. The incidence of hypercortisolism was greatest if an adenoma was identified at surgery and the patient received selective adenomectomy (19, or 95% of 20 patients), if there was evidence at surgery or by preoperative CT scanning that the previous surgical exposure of the pituitary was incomplete (seven, or 78% of nine patients), if an adenoma was seen on preoperative CT scanning (three of three patients), or if the patient had had prior pituitary irradiation without surgery (two of two patients). In contrast, only five (42%) of 12 patients who received subtotal or total hypophysectomy had remission of hypercortisolim. Surgically induced hypopituitarism occurred in six (50%) of these 12 patients, but in only one (5%) of the 20 patients who underwent selective adenomectomy. Three (13%) of the 24 patients who were in remission from hypercortisolims following repeat surgery developed recurrent hypercortisolism 10 to 47 months postoperatively. Repeat transsphenoidal exploration of the pituitary and treatment limited to selective adenomectomy should be considered in patients with hypercortisolism despite previous pituitary treatment. If an adenoma is identified during surgery, the chance of remission of Cushing's disease is high and the risk of hypopituitarism is low; however, if no adenoma can be found and partial or complete hypophysectomy is performed, remission of hypercortisolism is less likely and the risk of hypopituitarism is about 50%. .A Friedman RB; Oldfield EH; Nieman LK; Chrousos GP; Doppman JL; Cutler GB Jr; Loriaux DL. .I 201784 .U 90011297 .S J Neurosurg 9001; 71(4):528-33 .M Antigens, CD/AN; Brain Neoplasms/*PA/SU; Female; Flow Cytometry; Glioma/*PA/SU; Human; Lymphocytes/IM/*PA; Male; Middle Age; Monocytes/*PA; Phenotype; Reference Values; Support, Non-U.S. Gov't. .T Characterization of lymphoid cells isolated from human gliomas. .P JOURNAL ARTICLE. .W To analyze the phenotypic profile of lymphoid cells freshly isolated from surgically resected human gliomas, a double-immunostaining technique was developed which permitted the investigators simultaneously to distinguish between hematogenous and tumor cell populations and to detect expression of lymphocyte-monocyte subset-specific antigens on hematogenous cells. With this technique, the profiles of tumor-infiltrating lymphocytes (TIL's) derived from high- and low-grade gliomas were compared with phenotypes of lymphocytes concurrently isolated from peripheral blood. The total leukocyte cell yield from high-grade glioma cases exceeded that of low-grade cases. In nine high-grade glioma cases the proportion of CD8-positive cells was increased within the TIL population (41.2% +/- 1.9%, mean +/- standard error of the mean) as compared to the corresponding peripheral blood lymphocyte (PBL) population (30.8% +/- 4.1%, p less than 0.05). The proportion of natural killer HNK-positive cells, some of which bear the CD8 antigen (although not necessarily the pan T cell antigens CD2 and CD3), was also increased in the TIL's (41.9% +/- 4.2%) compared to that found in PBL's (32.1 +/- 5.6%, p less than 0.05) of high-grade glioma cases. The observed phenotypic pattern of high-grade glioma TIL's is similar to that reported based on immunohistochemical analysis of tumor tissue sections, suggesting that the techniques described here resulted in isolation of lymphoid cells representative of TIL's. .A Farmer JP; Antel JP; Freedman M; Cashman NR; Rode H; Villemure JG. .I 201785 .U 90011298 .S J Neurosurg 9001; 71(4):534-7 .M Acetylcholinesterase/AN; Biological Markers/AN; Brain/*PA; Case Report; Cerebral Hemorrhage/*PA/RA/SU; Female; Hippocampus/*PA; Human; Male; Middle Age; Neuronal Plasticity/*; Synapses/PH/*UL. .T Synaptic reorganization within the human central nervous system following injury [see comments] .P JOURNAL ARTICLE. .W Behavioral recovery following brain injury in humans is well recognized; however, the anatomical basis for such recovery has not been demonstrated. Two cases are presented that show reorganization of synaptic connections (plasticity) in the dentate gyrus of human brain following uncal herniation. The neurohistological appearance of these cases is very similar to a well-described animal model of anatomical, physiological, and behavioral recovery following experimental surgical injury. .A Grady MS; Jane JA; Steward O. .I 201786 .U 90011299 .S J Neurosurg 9001; 71(4):538-44 .M Adult; Aged; Autoradiography; Binding, Competitive; DNA Replication/DE; Epidermal Growth Factor-Urogastrone/*ME/PD; Female; Human; Insulin-Like Growth Factor I/*ME/PD; Iodine Radioisotopes; Kinetics; Male; Meningeal Neoplasms/ME/*PA/SU; Meningioma/ME/*PA/SU; Middle Age; Receptors, Endogenous Substances/*AN/ME; Receptors, Epidermal Growth Factor-Urogastrone/*AN/ME; Recombinant Proteins/ME; Somatomedins/*ME. .T Characterization of insulin-like growth factor I and epidermal growth factor receptors in meningioma. .P JOURNAL ARTICLE. .W Receptors for insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) were localized and characterized in eight samples of human meningioma (four fibrous, two meningothelial, and two angioblastic types), using quantitative autoradiographic techniques. Effects of both growth factors on deoxyribonucleic acid (DNA) synthesis in the cultured meningioma cells were examined. High numbers of specific binding sites for both IGF-I and EGF were homogeneously present in tissue sections derived from fibrous and meningothelial types of meningiomas, whereas binding sites for these growth factors were not detectable in adjacent leptomeninges. While relatively large numbers of IGF-I binding sites were located in the wall of the intratumoral vasculature, the number of binding sites in the stromal component was lower in angioblastic-type meningiomas, including a low number of EGF binding sites detected only in the stromal portion. Scatchard analysis revealed the presence of a single class of high-affinity binding sites for both IGF-I and EGF in the meningiomas examined (dissociation constant (Kd) = 0.6 to 2.9 nM, and the maximum number of binding sites (Bmax) = 16 to 80 fmol/mg for IGF-I; and Kd = 0.6 to 4.0 nM, Bmax = 3 to 39 fmol/mg for EGF). Both growth factors increased the synthesis of DNA, in a dose-dependent manner, as measured by 3H-thymidine incorporation. The combination of IGF-I and EGF synergistically stimulated the synthesis of DNA, and the effects seen with 10% fetal bovine serum could be reproduced at a concentration of 10(-10) M. These observations can be interpreted to mean that both IGF-I and EGF may be involved in the growth modulation of meningiomas, possibly through paracrine or autocrine mechanisms. .A Kurihara M; Tokunaga Y; Tsutsumi K; Kawaguchi T; Shigematsu K; Niwa M; Mori K. .I 201787 .U 90011300 .S J Neurosurg 9001; 71(4):545-50 .M Animal; Cell Division; Female; Human; Male; Meningeal Neoplasms/BS/*PA; Meningioma/BS/*PA; Mice; Mice, Nude; Neoplasm Transplantation; Neovascularization; Subrenal Capsule Assay; Support, U.S. Gov't, P.H.S.; Transplantation, Heterologous. .T Implantation of human meningiomas into the subrenal capsule of the nude mouse. A model for studies of tumor growth. .P JOURNAL ARTICLE. .W To develop a reproducible in vivo model for the growth of human meningiomas, meningiomas from 16 patients were implanted into the subrenal capsule of the nude mouse. In eight experiments solid tumor implants taken directly from surgical specimens were used, in four experiments the implants were made from early-passage monolayer cell cultures, and in four experiments both techniques were used. Successful tumor growth was observed in 10 (83%) of the 12 solid tumor implants and in six (75%) of the eight implants from cell cultures. The size and neovascularization of these tumors were serially determined over a 3-month period. Tumor doubling occurred in 1 to 3 weeks in all of the solid tumor implant group. In the group of six tumors successfully implanted from cell cultures, three doubled in 1 to 3 weeks and three grew more rapidly, reaching 10 to 20 times their original volume. Neovascularity occurred in the tumors within 3 weeks of implantation. Each of the solid tumor implants had a histological pattern similar to that of the corresponding original specimen. Only three of those implanted from cell cultures were similar to the original tumor; the other three displayed features characteristic of malignant meningioma. These studies suggest that implantation of human meningiomas in the subrenal capsule of the nude mouse is a feasible model that may be useful for evaluating hormonal or genetic modulation of tumor growth and for testing potential treatment regimens. .A Medhkour A; Van Roey M; Sobel RA; Fingert HJ; Lee J; Martuza RL. .I 201788 .U 90011302 .S J Neurosurg 9001; 71(4):558-64 .M Animal; Basilar Artery/DE/*PH; Calcitonin Gene-Related Peptide/*PD; Cerebral Arteries/DE/*PP; Cerebral Ischemia, Transient/*PP; Dogs; Female; In Vitro; Male; Muscle, Smooth, Vascular/DE/*PH; Reference Values; Subarachnoid Hemorrhage/*PP; Vasoconstriction/*DE. .T Relaxant effect of calcitonin gene-related peptide on cerebral arterial spasm induced by experimental subarachnoid hemorrhage in dogs. .P JOURNAL ARTICLE. .W This study examines the relaxant effect of calcitonin gene-related peptide (CGRP), a 37-amino acid peptide with a potent vasodilator action, on cerebral arterial spasm after subarachnoid hemorrhage (SAH). The spasm was induced by injecting autologous arterial blood percutaneously into the cisterna magna in adult mongrel dogs. The single-injection model of SAH was produced by injection of 1.0 ml/kg body weight of blood (on Day 0), and the double-injection model involved two successive injections of 0.5 ml/kg body weight of blood made 48 hours apart (on Day 0 and Day 2). On vertebral angiograms, arterial narrowing of the major cerebral arteries was most prominent on Day 3 after SAH in the single-injection model and on Day 7 in the double-injection model. When 10(-10) mol/kg of CGRP was administered intracisternally in the single-injection model on Day 3, the diameter of the spastic cerebral arteries, as determined by angiography, recovered to normal. After intracisternal administration of 10(-11) to 2 X 10(-10) mol/kg of CGRP on Day 7 in double-injection models, spastic cerebral arteries dilated in a dose-dependent manner. The dilatory effect of CGRP continued for a few hours after administration. The results suggest that CGRP injected intracisternally may reverse cerebral arterial spasm after SAH. .A Nozaki K; Uemura Y; Okamoto S; Kikuchi H; Mizuno N. .I 201789 .U 90011303 .S J Neurosurg 9001; 71(4):565-72 .M Alcohol, Ethyl/PD; Animal; Brain Injuries/*MO/PC/PP; Indomethacin/*PD; Rats; Rats, Inbred Strains; Support, U.S. Gov't, P.H.S.. .T Effect of indomethacin pretreatment on acute mortality in experimental brain injury. .P JOURNAL ARTICLE. .W The effect of indomethacin administration on the mortality rate of brain-injured rats was studied in four groups of animals subjected to a level of injury with a fluid-percussion apparatus predetermined to cause 50% mortality (50% lethal dose, or LD50). There were 24 animals in each of the following groups: 1) a control group, on which the LD50 was evaluated; 2) an ethanol-treated group with a mean blood serum level of 0.32 +/- 0.03 gm% (+/- standard error of the mean); 3) an indomethacin-treated group at a dose level of 3 mg/kg body weight administered intraperitoneally 10 to 15 minutes before injury; and 4) an indomethacin/ethanol-treated group. Significant differences in mortality rates were found in these experimental groups; namely, 50%, 58%, 8.3% (p less than 0.005), and 25% (p less than 0.05), respectively. The predetermined LD50 level of a 2.5- to 2.6-atm peak pressure pulse produced immediate apnea in all animals, which was either sustained (Type III), followed by temporary respiratory recovery (Type II), or followed by permanent resumption of breathing (Type I). The most important effect of indomethacin on respiratory function was manifested by a much higher percentage of Type I respiratory responses and a much lower percentage of Type II and III responses (hence a lower mortality rate). There was also a more rapid return to normal breathing in the postapneic period of recovery. Suppression of prostaglandin synthesis and of superoxide anion production at the of trauma may explain, at least in part, these favorable effects of indomethacin. .A Kim HJ; Levasseur JE; Patterson JL Jr; Jackson GF; Madge GE; Povlishock JT; Kontos HA. .I 201790 .U 90011304 .S J Neurosurg 9001; 71(4):573-7 .M Animal; Brain Injuries/DT/PP/*TH; Combined Modality Therapy; Male; Rats; Rats, Inbred Strains; Respiration; Respiration, Artificial/*; Superoxide Dismutase/*TU; Support, U.S. Gov't, P.H.S.. .T Combined effect of respirator-induced ventilation and superoxide dismutase in experimental brain injury. .P JOURNAL ARTICLE. .W The function-specific enzyme superoxide dismutase (SOD) was tested for its protective effect in severe experimental fluid-percussion brain injury (4.45 +/- 0.10 atm) in 30 of 60 randomly selected male Sprague-Dawley rats. A respirator was used only in the event of need. The number of animals with permanent resumption of spontaneous breathing (Type I respiratory response) remained essentially the same in each group. However, when Type II apnea (cannot maintain recovery) and Type III apnea (never recovers from the initial apnea) were terminated with a respirator, all rats with Type II responses from each group were successfully converted to a state of sustained spontaneous breathing. In contrast, only five (41.7%) of the 12 rats with Type III response were salvaged in the control group while five (83.3%) of six Type III rats in the SOD-treated group were saved. The results reveal the nature of the therapeutic effectiveness of superoxide radical scavengers in the overall outcome of head injury in this animal model. While SOD alone did not increase the number of spontaneous survivors, the drug shifted a number of animals from the critically injured rats with Type III respiratory response to the less critical Type II condition. Whereas induced respiration as the sole therapy in the control group lowered the mortality rate to 23.3%, respiratory assistance together with SOD treatment reduced the "mortality" to a single animal with Type III apnea (3.3%) which was alive but still required the respirator after 2 hours (p less than 0.001). The results show that respiratory assistance alone accounted for a 33% decrease in mortality rate and that SOD, given in addition to induced ventilation, further decreased mortality by 20%. Since SOD enzymes are reactively specific for superoxide, the increased survival rate of the brain-injured rat must have been due either to preventing or to minimizing pathophysiological changes, probably in the brain stem, caused by oxygen free radicals. .A Levasseur JE; Patterson JL Jr; Ghatak NR; Kontos HA; Choi SC. .I 201791 .U 90011306 .S J Neurosurg 9001; 71(4):588-93 .M Adipose Tissue/*PH; Animal; Female; Microscopy, Electron; Nerve Endings/UL; Nerve Regeneration/*/PH; Rats; Rats, Inbred Strains; Sciatic Nerve/PH/*TR; Surgical Flaps; Transplantation, Heterotopic. .T The influence of fat tissue on neuroma formation. .P JOURNAL ARTICLE. .W The proximal stumps of transected sciatic nerves were implanted into an abdominal pedicle flap of fat tissue in rats. Nerve stumps that had been transected without implantation into fat tissue served as control experiments. At 4, 8, or 24 weeks postoperatively, the rats were sacrificed and the neuromas at the transected nerve ends together with the adjacent fat tissue were studied after intra-aortal perfusion fixation. Light microscopy revealed no significant difference in neuroma size between the two groups. In most animals with fat implantation, however, infiltration of fat tissue beyond the margins of the solid neuromatous bulb by regenerating nerve fibers was limited to rare axons growing along blood vessels and connective tissue strands. In only a few instances was the fat tissue itself invaded by minifascicles as was usually seen in the connective tissue surrounding control neuromas. It is concluded that diffuse outgrowth of nerve fibers is limited to some extent by fat tissue, which, however, is not an impermeable barrier for regenerating nerve fibers. Nevertheless, in a fat tissue flap, the neuroma is placed in a "soft pressure-free bed" which might be a prerequisite for permanent diminution of pain sensitivity. .A Weis J; Schroder JM. .I 201792 .U 90011307 .S J Neurosurg 9001; 71(4):594-600 .M Animal; Blood Glucose/*ME; Deoxyglucose/PD; Hexokinase/AI; Hyperglycemia/CO/ME/*PP; Ischemia/PP; Male; Methylglucosides/*PD; Methylglycosides/*PD; Monosaccharide Transport Proteins/ME; Paraplegia/CO/ME/*PP; Rats; Rats, Inbred Strains; Reference Values; Spinal Cord/BS; Support, U.S. Gov't, Non-P.H.S.. .T The role of glucose uptake and metabolism in hyperglycemic exacerbation of neurological deficit in the paraplegic rat. .P JOURNAL ARTICLE. .W Previous studies indicate that hyperglycemia, particularly that induced by exogenous glucose administration, exacerbates neurological deficits in the rat spinal cord ischemic model. The effect of inhibition of glucose uptake (glucose transporter) and initial metabolism (hexokinase) on neurological outcome was evaluated in the present investigation using the competitive inhibitors 2-deoxyglucose (2-DG) and 3-O-methylglucose (3-OMG). Sprague-Dawley rats, weighing 200 to 300 gm each, received either 0.25, 1, or 2 gm/kg 2-DG; 2 gm/kg 3-OMG; 2 gm/kg glucose; or an equivalent volume of 0.9% saline intraperitoneally. Rats were intubated and ventilated with 1% to 1.5% halothane. The aortic arch was exposed and snares were placed on the right and left subclavian arteries and the aorta distal to the left subclavian artery. The three vessels were occluded for 10, 11, 12, or 13 minutes. Lower-extremity neurological deficits were evaluated at 1, 4, 18, and 24 hours postocclusion based on a 15-point scale (normal = 0, severe deficit = 15). Lower-extremity neurological deficits were significantly less severe in the groups treated with 2-DG (0.25 and 1 gm/kg) at 18 and 24 hours postocclusion (p less than 0.05 for 0.25 gm/kg and p less than 0.005 for 1 gm/kg, Student's t-test with Bonferroni correction). The lower 2-DG dose of 0.25 gm/kg did not significantly increase the plasma glucose level, suggesting that the glucose transporter was not markedly inhibited, and that the improved neurological outcome was more likely due to inhibition of hexokinase. The higher 2-DG dose of 1 gm/kg afforded protection despite significantly increasing the plasma glucose level, implying a strong inhibition of both the glucose transporter and hexokinase. Administration of 3-OMG, which only inhibits glucose uptake and not hexokinase, actually worsened the neurological deficit in a manner similar to that observed in rats treated with glucose. The authors conclude that the activity of the glucose transporter by itself does not significantly contribute to hyperglycemic exacerbation of neurological deficits. In contrast, the hexokinase step, at least in combination with the transporter and possibly alone, plays a significant role in hyperglycemic exacerbation of the lower-extremity neurological deficit in the paraplegic rat. .A LeMay DR; Zelenock GB; D'Alecy LG. .I 201793 .U 90011309 .S J Neurosurg 9001; 71(4):605-7 .M Brain Edema/*CI/RA; Case Report; Cerebral Hemorrhage/ET/SU; Coma/*CI; Craniotomy; Cyanides/PO; Ferricyanides/*AE; Hematoma/ET/SU; Human; Hypertension/CO/*DT; Infusions, Intravenous; Male; Middle Age; Nitroprusside/AD/*AE/TU; Propranolol/TU. .T Delayed postoperative neurological deterioration from prolonged sodium nitroprusside administration. Case report. .P JOURNAL ARTICLE. .W Sodium nitroprusside is commonly used for the induction of hypotension during neurosurgical procedures. Its toxicity stems from hemodynamic compromise as well as from its metabolites, especially the formation of cyanide. A patient is described who underwent craniotomy for hypertensive intracerebral hemorrhage. He gradually recovered following the operation, but needed continued administration of sodium nitroprusside for control of hypertension. On the 7th postoperative day, he deteriorated into coma with evidence of severe edema and herniation on the computerized tomography scan. Cessation of sodium nitroprusside and treatment for cyanide poisoning resulted in resolution of his symptoms within hours. The potential toxicity of sodium nitroprusside, measures to prevent toxicity, and therapeutic steps are discussed. .A Ram Z; Spiegelman R; Findler G; Hadani M. .I 201794 .U 90011310 .S J Neurosurg 9001; 71(4):608-10 .M Adult; Atrophy; Brain/PA/RA; Brain Injuries/PA/*RA; Case Report; Head Injuries/CO/*RA; Human; Magnetic Resonance Imaging; Male; Paralysis/ET. .T Delayed nonhemorrhagic encephalopathy following mild head trauma. Case report. .P JOURNAL ARTICLE. .W Delayed nonhemorrhagic encephalopathy following mild head trauma is a rare condition with an unknown etiology. The few cases reported in the literature are in young adults, all of them in the era before computerized tomography (CT) became available, and all had a devastating clinical course with multifocal ischemia or necrotic lesions found at autopsy. A case is presented of a young man with this syndrome who survived the acute encephalopathic phase with severe residual neurological deficits. Repeat CT scans during and following the acute phase as well as magnetic resonance imaging showed diffuse multifocal lesions compatible with ischemic changes and demyelination in the "watershed" areas of the brain. .A Ram Z; Hadani M; Spiegelman R; Tadmor R; Shacked I. .I 201795 .U 90011311 .S J Neurosurg 9001; 71(4):611-5 .M Adolescence; Case Report; Female; Human; Male; Neuroma, Acoustic/RA/*SU; Neurosurgery/MT; Skull; Tomography, X-Ray Computed. .T Surgical removal of giant acoustic neurinomas involving the skull base. Report of two cases [see comments] .P JOURNAL ARTICLE. .W Neurinomas arising from the peripheral branch of the acoustic nerve distal to the internal auditory canal in the temporal bone are rare. Two advanced skull-base neurinomas are described which were situated mainly in the temporal petrous bone, and extended to the parapharyngeal space anteriorly, to the lateral cervical portion inferiorly, into the sphenoidal sinus medially, and into the middle and posterior cranial fossae compressing the brain stem. Both patients had been deaf for several years without other neurological deficits. The operative findings revealed that the fifth, seventh, and caudal cranial nerves were intact; therefore, it was suspected that these neurinomas originated primarily within the cochlea or the vestibule in the temporal bone. The tumors were completely removed via an extradural approach, with good results. Since the surgical treatment of such advanced skull-base neurinomas is difficult, the operative infratemporal fossa approach is described in detail. .A Sawamura Y; Nakagawa Y; Ikota T; Abe H. .I 201796 .U 90011312 .S J Neurosurg 9001; 71(4):616-7 .M Basal Ganglia/*PA; Case Report; Child; Female; Human; Magnetic Resonance Imaging; Medulla Oblongata/PA; Putamen/PA; Pyramidal Tracts/PA; Syringomyelia/DI/PA/*SU. .T Syringomyelia extending to the basal ganglia. Case report [see comments] .P JOURNAL ARTICLE. .W A 10-year-old girl was admitted to the hospital with complaints of progressive right hemiparesis and sensory disturbance. Magnetic resonance imaging revealed a Chiari Type I malformation and syringomyelia from T-10 to C-1. The syrinx extended from the medulla to the right putamen along the pyramidal tract. .A Okada S; Nakagawa Y; Hirakawa K. .I 201797 .U 90011313 .S J Neurosurg 9001; 71(4):618-9 .M Case Report; Child; Craniotomy/*AE/MT; Edema/*ET; Human; Male; Muscles/IR/RA; Muscular Diseases/*ET; Neuroma, Acoustic/*SU; Paralysis/*ET; Posture; Sciatic Nerve/PP; Tomography, X-Ray Computed. .T A hazard of craniotomy in the sitting position: the posterior compartment syndrome of the thigh. Case report. .P JOURNAL ARTICLE. .W A bilateral posterior compartment syndrome of the thigh with a sciatic neuropathy in a patient following a craniotomy in the sitting position is described. The pathophysiology of the sciatic nerve dysfunction is discussed and the diagnostic value of computerized tomography is emphasized. Prompt decompression of the nerve is suggested. .A Poppi M; Giuliani G; Gambari PI; Acciarri N; Gaist G; Calbucci F. .I 201798 .U 90011314 .S J Neurosurg 9001; 71(4):620-2 .M Brain/PA; Case Report; Female; Human; Hydrocephalus/ET/PA/*SU; Magnetic Resonance Imaging; Meningitis, Listeria/*CO; Middle Age; Spinal Cord Compression/ET/*SU; Ventriculostomy/MT. .T Symptomatic hydrocephalus and reversible spinal cord compression in Listeria monocytogenes meningitis. Case report. .P JOURNAL ARTICLE. .W Central nervous system infections with Listeria monocytogenes result in varied clinical syndromes ranging from meningitis to rhomboencephalitis. A case of Listeria meningitis complicated by symptomatic communicating hydrocephalus and hydrostatic cervical cord compression is presented which clinically and radiographically improved with aggressive ventricular drainage. .A Raps EC; Gutmann DH; Brorson JR; O'Connor M; Hurtig HI. .I 201799 .U 90011315 .S J Neurosurg 9001; 71(4):623-5 .M Child, Preschool; Craniosynostoses/*SU; Human; Infant; Posture; Skull/*SU; Support, U.S. Gov't, P.H.S.; Surgery, Plastic/MT. .T Vacuum-stiffened beanbag for cranial remodeling procedures in modified prone position. Technical note. .P JOURNAL ARTICLE. .W In surgical correction of multiple-suture synostosis, placing the patient in the modified prone position permits access to the calvarium from the supraorbital ridge to the occipital bone below the transverse sinus. The modified prone position thereby enables surgeons to perform cranial remodeling procedures at one stage under direct vision, contributing to improved surgical results. However, no satisfactory head-frame for this position has been available. The authors report the successful use of a vinyl bag filled with styrofoam beads to achieve the modified prone position in young children. This widely available, economical device provides a safe, reliable means of positioning the child's head for cranial remodeling procedures. .A Park TS; Broaddus WC; Harris M; Persing JA; Jane JA. .I 201800 .U 90011316 .S J Neurosurg 9001; 71(4):629 .M Acrylic Resins/*TO; Animal; Biocompatible Materials/*TO; Dogs; Dura Mater/BS/*PA; Neovascularization; Surgical Mesh. .T Reactions to dural substitutes [letter; comment] .P COMMENT; LETTER. .A Guthkelch AN; Huhn S; Chvapil M. .I 201801 .U 90011318 .S J Neurosurg 9001; 71(4):630-1 .M Hemostasis, Surgical/*MT; Human; Neurosurgery/MT; Scalp/BS/*SU; Sutures/*. .T Techniques to control bleeding from scalp incisions [letter; comment] .P COMMENT; LETTER. .A Viswanathan R. .I 201802 .U 90011331 .S J Nucl Med 9001; 30(10):1579-81, 1586 .M Referral and Consultation/*LJ; Societies, Medical/*; United States. .T The Stark referrals bill--wanted oversight or wasteful overkill? .P JOURNAL ARTICLE. .A Tilyou SM. .I 201803 .U 90011332 .S J Nucl Med 9001; 30(10):1584-5 .M Government Agencies/*; Nuclear Medicine/*; Quality Assurance, Health Care/*; United States. .T NRC workshop participants discuss the Part 35 petition and the QA rule [news] .P NEWS. .A Marcus CS. .I 201804 .U 90011334 .S J Nucl Med 9001; 30(10):1607-15 .M Aged; Aged, 80 and over; Aging/*PA; Alzheimer's Disease/*DI/RA/RI; Brain/PA/RA/RI; Comparative Study; Glucose/DU; Human; Magnetic Resonance Imaging/*; Middle Age; Support, U.S. Gov't, P.H.S.; Tomography, Emission-Computed/*; Tomography, X-Ray Computed/*. .T Comparison of CT, MR, and PET in Alzheimer's dementia and normal aging. .P JOURNAL ARTICLE. .W We compared the findings of computed tomography (CT), magnetic resonance (MR), and positron emission tomography (PET) scans of glucose metabolism in 30 patients with clinically diagnosed Alzheimer's Disease (DAT) to those noted in 25 age-matched normal controls. Mean ratings of cortical and ventricular atrophy on CT and of metabolic abnormality on PET were significantly different (p less than 0.001 and p less than 0.0001, respectively) between two subject groups, however, there was a considerable overlap in reading of cortical atrophy. CT hypodensities were present in 17% of DAT patients and 12% of controls. MR revealed numerous additional periventricular and deep white matter signal changes. Neither hypodensities nor hyperintensities were correlated with PET abnormalities. Although, not infrequently, hypometabolic areas on PET scans corresponded to atrophic regions on anatomic images, they also occurred without such changes. Interestingly, cortical high signal intensity seen on MRI was frequently observed to be associated with areas of hypometabolism. Our results suggest that PET may be the most sensitive modality for detecting cortical involvement in DAT. .A Fazekas F; Alavi A; Chawluk JB; Zimmerman RA; Hackney D; Bilaniuk L; Rosen M; Alves WM; Hurtig HI; Jamieson DG; et al. .I 201805 .U 90011335 .S J Nucl Med 9001; 30(10):1616-20 .M Adult; Brain/*BS/RI; Frontal Lobe/BS/RI; Human; Iodine Radioisotopes/*DU; Male; Middle Age; Regional Blood Flow; Schizophrenia/*RI; Support, U.S. Gov't, Non-P.H.S.; Tomography, Emission-Computed, Single-Photon/*. .T Quantitative iodine-123 IMP imaging of brain perfusion in schizophrenia. .P JOURNAL ARTICLE. .W Decreased perfusion in the frontal lobes of patients with chronic schizophrenia has been reported by multiple observes using a variety of techniques. Other observers have been unable to confirm this finding using similar techniques. In this study quantitative single photon emission computed tomography brain imaging was performed using p,5n [123I]IMP in five normal subjects and ten chronically medicated patients with schizophrenia. The acquisition data were preprocessed with an image dependent Metz filter and reconstructed using a ramp filtered back projection technique. The uptake in each of 50 regions of interest in each subject was normalized to the uptake in the cerebellum. There were no significant confirmed differences in the comparable ratios of normal subjects and patients with schizophrenia even at the p = 0.15 level. "Hypofrontality" was not observed. .A Cohen MB; Lake RR; Graham LS; King MA; Kling AS; Fitten LJ; O'Rear J; Bronca GA; Gan M; Servrin R; et al. .I 201806 .U 90011336 .S J Nucl Med 9001; 30(10):1621-6 .M Brain/BS/RI; Brain Death/*RI; Brain Injuries/*RI; Human; Organotechnetium Compounds; Oximes; Radionuclide Angiography; Regional Blood Flow. .T Clinical use of technetium-99m HM-PAO for determination of brain death. .P JOURNAL ARTICLE. .W We report our clinical experience with the use of [99mTc]hexamethyl propyleneamine oxime (HM-PAO) in establishing a diagnosis of brain death in 11 patients following trauma to the head and four patients who suffered atraumatic injuries. In 9/15 studies there was no intracranial flow present and brain death was then confirmed by standard criteria. Of the remaining 6/15 studies which showed evidence of cerebral perfusion, 3/6 patients underwent a subsequent HM-PAO study which showed cessation of perfusion. One additional patient died of pneumonia and two patients survived. Thus, in all cases where there was no flow present the diagnosis of brain death was later confirmed whereas three patients clinically thought to be brain dead showed significant perfusion and survived the cerebral trauma. HM-PAO may be useful in determination of brain death because it provides unequivocal results, can be performed by planar imaging at the bedside, and does not require withdrawal of medical therapy, thus allowing a diagnosis to be established more rapidly. .A Reid RH; Gulenchyn KY; Ballinger JR. .I 201807 .U 90011337 .S J Nucl Med 9001; 30(10):1627-35 .M Adolescence; Adult; Aged; Brain/*BS/RI; Brain Death/*RI; Brain Injuries/*RI; Child; Child, Preschool; Human; Infant; Middle Age; Organotechnetium Compounds; Oximes; Radionuclide Angiography; Regional Blood Flow; Retrospective Studies. .T Cerebral perfusion imaging with technetium-99m HM-PAO in brain death and severe central nervous system injury [see comments] .P JOURNAL ARTICLE. .W We performed 38 cerebral perfusion studies in 33 patients with brain death or with severe central nervous system injury using technetium-99m hexamethyl-propyleneamine oxime [( 99mTc]HM-PAO). Uptake by the cerebrum and/or cerebellium was present in all patients who were not clinically brain dead (ten studies) although the study was often abnormal. In those patients who were brain dead, 16/17 studies demonstrated no uptake in either the cerebrum or cerebellum. In patients suspected of brain death, but who had conditions interfering with the diagnosis the test demonstrated no uptake in 9/11 studies, confirming brain death. A radionuclide angiogram (RNA) of the head was also performed in 33/38 studies and showed complete agreement with the [99mTc]HM-PAO uptake, except in one case. We conclude that cerebral perfusion imaging with [99mTc]HM-PAO is a simple, noninvasive and reliable test to confirm brain death. By comparison with conventional technetium agents, [99mTc]HM-PAO is not dependent on the quality of the bolus injection, is easier to interpret and allows evaluation of posterior fossa blood flow. .A Laurin NR; Driedger AA; Hurwitz GA; Mattar AG; Powe JE; Chamberlain MJ; Zabel PL; Pavlosky WF. .I 201808 .U 90011338 .S J Nucl Med 9001; 30(10):1636-45 .M Adolescence; Adult; Aged; Alkaline Phosphatase/*IM; Antibodies, Monoclonal/AN/*DU/TU; Brain Neoplasms/*RI/TH; Female; Glioma/*RI/TH; Human; Iodine Radioisotopes/DU; Male; Middle Age; Placenta/EN; Pregnancy; Radionuclide Imaging; Receptors, Epidermal Growth Factor-Urogastrone/*IM; Support, Non-U.S. Gov't. .T Antibody guided diagnosis and therapy of brain gliomas using radiolabeled monoclonal antibodies against epidermal growth factor receptor and placental alkaline phosphatase. .P JOURNAL ARTICLE. .W Twenty-seven patients with brain glioma were scanned using 123I-labeled monoclonal antibodies against epidermal growth factor receptor (EGFR1) or placental alkaline phosphatase (H17E2). Successful localization was achieved in 18 out of 27 patients. Eleven out of 27 patients were also studied using a nonspecific control antibody (11.4.1) of the same immunoglobulin subclass and observable tumor localization was also achieved in five patients. The specificity of targeting was assessed by comparing images obtained with specific and nonspecific antibodies and by examining tumor and normal tissue biopsies after dual antibody administration. Ten patients with recurrent grade III or IV glioma who showed good localization of radiolabeled antibody were treated with 40-140 mCi of 131I-labeled antibody delivered to the tumor area intravenously (n = 5) or by infusion into the internal carotid artery (n = 5). Six patients showed clinical improvement lasting from 6 mo to 3 yr. One patient continues in remission (3 yr after therapy), but the other five who responded initially relapsed 6-9 mo after therapy and died. No major toxicity was attributable to antibody-guided irradiation. Targeted irradiation by monoclonal antibody may be clinically useful and should be explored further in the treatment of brain gliomas resistant to conventional forms of treatment. .A Kalofonos HP; Pawlikowska TR; Hemingway A; Courtenay-Luck N; Dhokia B; Snook D; Sivolapenko GB; Hooker GR; McKenzie CG; Lavender PJ; et al. .I 201809 .U 90011339 .S J Nucl Med 9001; 30(10):1646-56 .M Abdomen/RI; Adenocarcinoma/PA/*RI; Adult; Aged; Antibodies, Monoclonal/DU; Carcinoembryonic Antigen/IM; Colorectal Neoplasms/PA/*RI; Female; Human; Iodine Radioisotopes/DU; Liver/RI; Lung Neoplasms/PA/RI; Male; Middle Age; Neoplasm Metastasis; Pelvis/RI; Prospective Studies; Support, Non-U.S. Gov't. .T Clinical value of immunoscintigraphy in colorectal carcinoma patients: a prospective study. .P JOURNAL ARTICLE. .W Fifty-seven patients with suspected CEA-producing tumors were studied prospectively by radioimmunoscintigraphy (RIS) using a 123I-labeled anti-CEA monoclonal antibody (MAb) (essentially the F(ab')2 or Fab fragments) and emission computed tomography (ECT). Results of RIS were compared to those of a comprehensive diagnostic study. Final diagnosis was based on surgery, biopsy and autopsy (n = 39) or follow-up findings (n = 18). Three groups of patients were defined: Group A with suspected primary tumors (n = 11), Group B with probable (n = 19) and Group C with questionable (n = 27) tumor relapse. Eighty-eight per cent, 93% and 71% of the anatomic regions studied were correctly identified as being involved, and 97%, 97%, and 87% as being free from tumor in Groups A, B, and C, respectively. In the 27 patients from Group C with no definite diagnosis of relapse, and in whom diagnosis was most difficult, 38 tumor sites were involved. Of these, 21 were detected by both prospective RIS and repeated comprehensive study, six by RIS only and seven by conventional methods only. Four sites remained undetected by both approaches. Ten of the 21 lesions were detected by RIS more than 1 mo earlier than by any other method. Among the seven tumor sites detected by other diagnostic modalities only, three were identified at the time of RIS and four became positive more than 6 mo later. Overall diagnosis was entirely correct in 30, partially correct in 16 and incorrect in six patients studied. RIS with ECT and 123I-labeled anti-CEA MAb allows early detection of recurrence or metastasis of colorectal cancer. It thus contributes to reduced delay between diagnosis and treatment. .A Bischof-Delaloye A; Delaloye B; Buchegger F; Gilgien W; Studer A; Curchod S; Givel JC; Mosimann F; Pettavel J; Mach JP. .I 201810 .U 90011340 .S J Nucl Med 9001; 30(10):1657-65 .M Adult; Aged; Aorta/*PP/RI; Blood Pressure Determination/*MT; Heart/PP/*RI; Heart Rate; Human; Male; Middle Age; Myocardial Infarction/*PP; Radionuclide Ventriculography/*. .T Radionuclide ventriculography and central aorta pressure change in noninvasive assessment of myocardial performance. .P JOURNAL ARTICLE. .W Systolic pressure-volume diagrams were obtained noninvasively by measuring the systolic central aortic pressure with a new device and by combining the pressure measurements, thus obtained, with absolute volume measurements obtained by radionuclide ventriculography during ejection. By dividing the peak power by the time elapsed from the beginning of ejection to the peak power point, the ejection rate of change of power (ERCP) was calculated. The ability of this index to assess left ventricular function at rest and exercise was evaluated in ten healthy subjects. ERCP proved to be more sensitive than global left ventricular ejection fraction increasing fivefold from rest to exercise compared with only 20% increase in global ejection fraction. ERCP increased dramatically postexercise from 3411 +/- 2173 to 18,162 +/- 14,633 gm/sec2, median 12,750, 95% confidence interval 9700-29,600, in healthy, while in patients it increased twofold from 2637 +/- 824 to 5062 +/- 1897 gm/sec2, median 4070, 95% confidence interval 2800-7030, p less than 0.001. ERCP had an excellent discriminative power in differentiating healthy subjects from patients, having 100% sensitivity, 90% specificity, 95% accuracy, 95% positive predictive value, and 90% negative predictive value. Thus, this noninvasive index seems to have a more comprehensive ability to evaluate changes in left ventricular function and shows a promising potential for clinical applications. .A Marmor A; Sharir T; Ben Shlomo I; Beyar R; Frenkel A; Front D. .I 201811 .U 90011341 .S J Nucl Med 9001; 30(10):1666-75 .M Models, Structural; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tomography, Emission-Computed, Single-Photon/*MT. .T Investigation of causes of geometric distortion in 180 degrees and 360 degrees angular sampling in SPECT. .P JOURNAL ARTICLE. .W To investigate geometric distortion when 180 degrees or 360 degrees angular sampling techniques are used in single photon emission computed tomography (SPECT), a study of point sources imaged at different positions in a water filled cylindrical phantom, and reconstructed using filtered back projection, was conducted. A simulation study, based upon a serial model of the system point spread function (PSF), was used to investigate the contributions of attenuation, spatial resolution and scatter on distortion of the reconstructed PSFs. To study the geometric distortion in transverse (x-y plane), coronal (x-z plane), and sagittal (y-z plane) sections, the ratios of the full widths at half maximum (FWHM) and full widths at tenth maximum (FWTM) in the x/y, x/z, and y/z directions were calculated for the real and simulated PSFs. These results showed that, in an attenuating medium, there is more distortion of point sources into ovals for 180 degrees than for 360 degrees sampling. The simulation study indicated that the primary cause of geometrical distortion in SPECT studies, is the inconsistency of projections due to variable attenuation and spatial resolution. The impact of scatter on geometric distortion was small as measured by the ratios of FWHMs and FWTMs for PSFs. Attenuation correction applied to acquired PSFs significantly reduced geometric distortion in both 180 degrees and 360 degrees studies. To investigate distortion in extended objects, an Iowa heart phantom was placed inside an Alderson body phantom and 201Tl heart SPECT studies acquired. The phantom images confirmed the conclusion that in transverse sections of 360 degrees studies with arithmetic averaging of opposite views, geometric distortion is reduced compared to 180 degrees. The coronal and sagittal sections were equally distorted in both, the 180 degrees and 360 degrees studies, and the 180 degrees studies yielded better contrast. .A Knesaurek K; King MA; Glick SJ; Penney BC. .I 201812 .U 90011342 .S J Nucl Med 9001; 30(10):1676-85 .M Animal; Brain Neoplasms/RI; Capillary Permeability/*; Comparative Study; Gallium Radioisotopes/*DU/PK; Indium Radioisotopes/*DU/PK; Iron Radioisotopes/*DU/PK; Male; Rats; Rats, Inbred Strains; Receptors, Transferrin/*AN; Serum Albumin/ME; Tissue Distribution; Transferrin/*DU. .T Comparison of iron-59, indium-111, and gallium-69 transferrin as a macromolecular tracer of vascular permeability and the transferrin receptor. .P JOURNAL ARTICLE. .W Tracer amounts of [59Fe++]citrate, [111In+++]chloride, and [68Ga+++]chloride were complexed with autologous plasma transferrin. Each of these complexes were co-administered with [125I]albumin by i.v. injection and their biodistribution was studied in Wistar rats. The plasma clearance of 59Fe and [125I]albumin was monoexponential with half-times of 49-70 and 277 min, respectively. The plasma clearance of 68Ga and 111In was biexponential with second component half-times of 157 and 232 min, respectively. Indium-111 tissue distribution was similar to that of [125I]albumin in heart, lung, muscle, brain and Walker-256 allograft. Iron-59 distribution spaces were generally the highest of the metal complexes in all tissues except muscle, where the 68Ga space was highest. The effects of transferrin-specific receptor-mediated endocytosis can be avoided in many organs and Walker-256 allografts by using the indium-transferrin complex, and the radiolabeled complex may be a convenient macromolecular tracer to estimate vascular permeability and vessel pore size in tumor and systemic tissue. In contrast, the iron-transferrin complex may be useful for measuring and imaging transferrin-specific receptors in brain and tumor tissue. .A Otsuki H; Brunetti A; Owens ES; Finn RD; Blasberg RG. .I 201813 .U 90011343 .S J Nucl Med 9001; 30(10):1686-92 .M Animal; Antibodies, Monoclonal/*DU; Indium Radioisotopes/*DU/PK; Kininase II/*IM; Lung/BS/*RI; Macaca mulatta; Rats; Rats, Inbred Strains; Tissue Distribution. .T Radioimmunoimaging of lung vessels: an approach using indium-111-labeled monoclonal antibody to angiotensin-converting enzyme. .P JOURNAL ARTICLE. .W A murine monoclonal antibody against human angiotensin-converting enzyme was radiolabeled with 111In via diethylenetriaminepentaacetic acid without substantial loss of antigen-binding capacity. This monoclonal antibody designated 9B9 cross-reacted with rat and monkey angiotensin-converting enzyme. Indium-111-labeled 9B9 selectively accumulated 10-20 times greater in the lung than in blood or other organs following intravenous administration in rats. Kinetics of lung accumulation and blood clearance were studied for 111In-9B9-antibody and compared to that of 125I-labeled 9B9 in rat. Highly specific accumulation of 111In-9B9-antibody in the lung of Macaca Rhesus monkeys after intravenous injection was monitored by gamma-imaging. Images of 111In-labeled antibody 9B9 biodistribution in monkey lung noticeably differ from the images of biodistribution of 99mTc-labeled albumin microspheres. This difference may provide information concerning the state of the endothelium of lung capillaries, which is different from the blood flow characteristics determined with routine microsphere technique. .A Danilov SM; Martynov AV; Klibanov AL; Slinkin MA; Sakharov IYu; Malov AG; Sergienko VB; Vedernikov AYu; Muzykantov VR; Torchilin VP. .I 201814 .U 90011344 .S J Nucl Med 9001; 30(10):1693-701 .M Animal; Antibodies, Monoclonal/*DU; Binding, Competitive; Chemistry; DTPA/*/PK; Human; Indium Radioisotopes/*DU/PK; Male; Melanoma/*RI; Mice; Mice, Nude; Support, U.S. Gov't, P.H.S.; Tissue Distribution. .T Reduction of background activities by introduction of a diester linkage between antibody and a chelate in radioimmunodetection of tumor. .P JOURNAL ARTICLE. .W A diester linkage was added between monoclonal anti-melanoma antibody 96.5 and a diethylenetriaminepentaacetic acid derivative to test if a tumor-to-blood and -to-organ ratio of the injected antibody in nude mice with human melanoma FEM XII xenografts could be increased by the addition of the readily cleavable linkage. Compared to the 111In-labeled antibody DTPA with a peptide linkage, the diester conjugate cleared much faster from the blood and was retained much less in muscle and normal organs such as liver, spleen and kidney over a 48-hr period. On the other hand, the activity retained in the tumor was larger than or similar to that of the peptide conjugate for this time period. This resulted in a 2.5, 2.1, and 2.6 fold increase in a tumor to blood, to liver and to kidney ratio at 48 hr for the diester conjugate as compared to the peptide conjugate. The whole-body biologic half life of the antibody was 36 hr, three times shorter than the peptide conjugate. The external imaging demonstrated a clearly visible tumor at 4 hr and a lower pool activity at 72 hr for the diester conjugate. The peptide conjugate, however, showed a persistant blood-pool activity at 72 hr. The addition of the diester linkage, therefore may be beneficial for imaging tumors in patients at early time intervals after injection. .A Paik CH; Yokoyama K; Reynolds JC; Quadri SM; Min CY; Shin SY; Maloney PJ; Larson SM; Reba RC. .I 201815 .U 90011345 .S J Nucl Med 9001; 30(10):1702-7 .M Amphetamines; Animal; Bile Ducts/*SU; Comparative Study; Dogs; Hemodynamics; Hypertension, Portal/*RI; Iodine Radioisotopes/*DU; Ligation; Liver Cirrhosis/ET; Propranolol/*AD; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Technetium Tc 99m Aggregated Albumin/DU. .T Portasystemic shunt fraction quantification using transrectal administration of iodine-123 iodoamphetamine in dogs with chronic bile duct ligation and after propranolol administration. .P JOURNAL ARTICLE. .W Following transrectal administration, 123I iodoamphetamine (IMP) has been shown in both animal and patient studies to be capable of detecting the presence of portasystemic shunting (PSS). However, the ability of this method to actually quantitate PSS in the presence of cirrhosis and propranolol has not been demonstrated. We studied nine dogs with hitologically proven cirrhosis induced by chronic bile duct ligation. After intravenous injection of propranolol, PSS were measured with both the IMP method and the standard of portal vein infusion of 99mTc macroaggregated albumin (MAA) given through a mesenteric vein catheter. Based on linear regression, a close relationship was seen, given by the equation: MAA = IMP 0.9 + 0.035, with correlation coefficient of 0.99. Thus, in dogs with cirrhosis secondary to chronic bile duct ligation and after propranolol administration, PSS can be quantitated with the transrectal IMP method. .A Yen CK; Koblik P; Breznock B; Komtebedde J; Pollycove M; Hornof WJ; Fisher P. .I 201816 .U 90011346 .S J Nucl Med 9001; 30(10):1708-12 .M Adult; Fatty Liver/*RI; Female; Human; Liver/ME/*RI; Male; Middle Age; Technetium Tc 99m Sulfur Colloid/DU; Xenon Radioisotopes/*DU/PK. .T Xenon-133 hepatic retention ratio: a useful index for fatty liver quantification. .P JOURNAL ARTICLE. .W Xenon-133 hepatic retention ratio was developed for quantifying fatty liver. Data were acquired in frame mode in the hepatic region and both lung bases for 5 min after rebreathing 20 mCi of gaseous 133Xe and for another 5 min during washout. Static [99mTc]sulfur colloid liver imaging was performed with the patient in the identical position immediately after the ventilation study and data were stored for liver localization. A hepatic time-activity curve corrected for background activity was generated. The 133Xe retention ratio was derived by dividing the activity at 3.5 min after washout by the peak activity. The data of 16 controls and 20 patients with fatty liver were analyzed. The retention ratio (mean +/- s.d.) was greatly increased in patients with fatty infiltration (0.43 +/- 0.20 vs. 0.04 +/- 0.08 in controls, p less than 0.001). There was a strong positive correlation between the 133Xe retention ratios and percentage of fat on biopsy as assessed by the amount of the liver tissue occupied by fat globules on H & E stained sections. The 133Xe hepatic retention ratio is a simple, accurate and clinically useful index of detecting, quantifying and managing fatty infiltration of the liver. .A Yeh SH; Wu LC; Wang SJ; Lin HC; Liu RS; Lee SD; Wu JC. .I 201817 .U 90011348 .S J Nucl Med 9001; 30(10):1718-22 .M Adult; Aged; False Positive Reactions; Female; Heart/*RI; Human; Male; Middle Age; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Thallium Radioisotopes/*DU; Tomography, Emission-Computed, Single-Photon/*MT. .T "Upward creep" of the heart: a frequent source of false-positive reversible defects during thallium-201 stress-redistribution SPECT. .P JOURNAL ARTICLE. .W A new cause of artifactual 201Tl defects on single photon emission computed tomography (SPECT) termed "upward creep" of the heart is described. In 102 consecutive patients undergoing 201Tl SPECT, 30 (29%) demonstrated upward creep defined by an upward movement of the heart of greater than or equal to 2 pixels during acquisition. In 45 consecutive patients with a less than 5% likelihood of coronary artery disease, 17 (38%) had upward creep. Of these nine had reversible 201Tl defects localized to the inferior and basal inferoseptal walls, while none of the 28 without upward creep had defects. The 17 low likelihood patients with upward creep had longer exercise duration and higher peak heart rate than those without upward creep. In five additional low likelihood patients with upward creep in whom imaging was immediately repeated, the upward creep pattern disappeared on the repeated images. After we changed our test protocol to begin imaging 15 min postexercise, only five (14%) of 36 low likelihood patients tested demonstrated upward creep. Upward creep is probably related to a transient increase in mean total lung volume early following exhaustive exercise, resulting in a mean lower position of the diaphragm (and thus the heart) at the beginning of imaging. The frequency of this source of false-positive 201Tl studies can be reduced by delaying SPECT acquisition until 15 min postexercise. .A Friedman J; Van Train K; Maddahi J; Rozanski A; Prigent F; Bietendorf J; Waxman A; Berman DS. .I 201818 .U 90011349 .S J Nucl Med 9001; 30(10):1723-6 .M Caffeine/BL/*TU; Case Report; Coronary Disease/CI/*DT/RI; Dipyridamole/*AE; Electrocardiography; Heart/PP/RI; Human; Male; Middle Age; Thallium Radioisotopes/DU. .T Caffeine reduces dipyridamole-induced myocardial ischemia. .P JOURNAL ARTICLE. .W The mechanism of action of coronary vasodilation after dipyridamole may be based on inhibition of cellular uptake of circulating endogenous adenosine. Since caffeine has been reported to be a competitive antagonist of adenosine we studied the effect of caffeine on the outcome of dipiridamole-201Tl cardiac imaging in one patient. During caffeine abstinence dipyridamole induced myocardial ischemia with down-slope ST depressions on the ECG, and reversible perfusion defects on the scintigrams. When the test was repeated 1 wk later on similar conditions, but now shortly after infusion of caffeine (4 mg/kg), the ECG showed no, and the scintigrams only slight signs of ischemia. We conclude that when caffeine abstinence is not sufficient, the widespread use of coffee and related products may be responsible for false-negative findings in dipyridamole-201Tl cardiac imaging. .A Smits P; Aengevaeren WR; Corstens FH; Thien T. .I 201819 .U 90011350 .S J Nucl Med 9001; 30(10):1727-30 .M Aged; Aneurysm, Dissecting/*RI; Aortic Aneurysm/*RI; Case Report; Female; Gated Blood-Pool Imaging; Human; Ventriculography, First-Pass. .T Radionuclide imaging in diagnosis of aortic dissection. .P JOURNAL ARTICLE. .W A case of an aortic dissection occurring in a 69-yr-old woman, 4 yr after aortic valve replacement is presented. The clinical context was one of an acute myocardial infarction. The first-pass and gated blood-pool scintigraphy ordered to evaluate cardiac function disclosed unexpected features of an aortic dissection clinically not suspected. .A Cote C. .I 201820 .U 90011351 .S J Nucl Med 9001; 30(10):1731-6 .M Bone Neoplasms/*RI/SC/TH; Brain Neoplasms/*RI/TH; Human; Lymphoma/*RI/TH; Monitoring, Physiologic. .T Nuclear medicine in monitoring response to cancer treatment. .P JOURNAL ARTICLE. .A Front D; Israel O. .I 201821 .U 90011352 .S J Nucl Med 9001; 30(10):1737 .M Models, Structural; Tomography, Emission-Computed, Single-Photon/*IS. .T Rotating slanthole collimater SPECT revisited [letter; comment] .P COMMENT; LETTER. .A Bauman JM; Bergh JR; Blumhardt R; Byrd BF; Cawthon MA; Gonzales AC; Hartshorne MF; Heironimus JD; Jackson RE; Lasher JC; et al. .I 201822 .U 90011353 .S J Nucl Med 9001; 30(10):1738-9 .M Comparative Study; Female; Human; Male; Pronation; Supination; Thallium Radioisotopes/*DU; Tomography, Emission-Computed, Single-Photon/*MT. .T Prone versus supine thallium-201 myocardial SPECT [letter; comment] .P COMMENT; LETTER. .A Esquerre JP. .I 201823 .U 90011354 .S J Nucl Med 9001; 30(10):1739 .M Backache/ET/*RI; Bone and Bones/*RI; Human; Lumbosacral Region/*SU; Spinal Fusion/*; Tomography, Emission-Computed, Single-Photon/*. .T Bone SPECT evaluation of patients with persistent back pain following lumbar spinal fusion [letter; comment] .P COMMENT; LETTER. .A Slizofski WJ. .I 201824 .U 90011355 .S J Nucl Med 9001; 30(10):1739-40 .M Human; Immunotherapy/*MT; Radioisotopes/*TU; Radiotherapy Dosage/*. .T Beta dose point kernels for radionuclides of potential use in radioimmunotherapy. .P JOURNAL ARTICLE. .I 201825 .U 90011385 .S J Nutr 9001; 119(9):1236-9 .M Animal; China; Heart Diseases/ET; Human; Nutrition Disorders/DT; Osteoarthritis/ET; Selenium/*DF/*PO/TU; Support, U.S. Gov't, P.H.S.. .T China, a country with both selenium deficiency and toxicity: some thoughts and impressions. .P JOURNAL ARTICLE. .A Whanger PD. .I 201826 .U 90011386 .S J Nutr 9001; 119(9):1240-5 .M Animal; Body Composition/*DE; Body Weight/DE; Dietary Carbohydrates/AN/*PD; Dietary Fats/AN/*PD; Energy Metabolism/DE; Male; Nitrogen/*ME; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't. .T Influence of dietary carbohydrate-to-fat ratio on whole body nitrogen retention and body composition in adult rats. .P JOURNAL ARTICLE. .W Experiments have shown that the amount and source of dietary energy may alter protein metabolism. A high fat diet has resulted in greater nitrogen retention than a high carbohydrate (CHO) diet. To examine this question further, adult rats were fed diets providing ratios of CHO:FAT as a percentage of energy of 0.5, 1.0, 1.5, 2.0, 2.5 or 3.0 for 6 wk. Mean energy and protein intakes were 93.0 +/- 0.8 kcal/d and 5.3 +/- 0.1 g/d, respectively. Final body weight was lower in rats fed the high fat diet (CHO:FAT, 0.5) than in rats fed the high carbohydrate diet (CHO:FAT, 3.0) (P less than 0.05), and a linear response was observed over the entire range of treatments (r = 0.92). Rats fed the high fat diet had the highest nitrogen balance; values were significantly (P less than 0.05) different from those of rats fed high carbohydrate diets (CHO:FAT, 2.0 or 2.5) when expressed as mg nitrogen/kcal energy gain. Rats fed the high fat diet had the highest protein gain and the lowest fat gain as a function of energy gain. It is concluded that alterations in nonprotein energy source result in metabolic changes, which may be related to adaptations in energy expenditure and/or protein deposition. .A McCargar LJ; Baracos VE; Clandinin MT. .I 201827 .U 90011387 .S J Nutr 9001; 119(9):1246-51 .M Animal; Bile Acids and Salts/ME; Blood Glucose; Cations/ME; Dietary Fiber/ME/*TU; Feces/AN; Hypercholesterolemia/*DH/ME; Male; Rabbits; Rats; Rats, Inbred Strains. .T Effects of neutral detergent fiber from blackgram (Phaseolus mungo) in rats and rabbits. .P JOURNAL ARTICLE. .W The hypocholesterolemic action of neutral detergent fiber (NDF) from blackgram (Phaseolus mungo) in rats may be due to hemicellulose, since removal of hemicellulose resulted in the loss of cholesterol-lowering action. Blackgram NDF showed different binding affinities for different bile acids, with maximum binding observed with chenodeoxycholic acid, and minimum binding with deoxycholic acid. Fecal excretion of inorganic cations (Mn++, Mg++, Cu++, Fe , Zn++, Na+ and K+) was greater in rats fed blackgram NDF than in rats fed a fiber-free diet. Absorption of glucose and cholesterol was lower in rabbits fed blackgram NDF than in rabbits fed a fiber-free diet. In vitro studies revealed significant binding of inorganic cations and bile acids by blackgram NDF. Cholic acid may be adsorbed on the surface of blackgram NDF. .A Indira M; Kurup PA. .I 201828 .U 90011388 .S J Nutr 9001; 119(9):1252-8 .M Adult; Aged; Body Weight; Cholesterol/BL; Dietary Fats/*AD; Female; Human; Male; Middle Age; Support, U.S. Gov't, Non-P.H.S.; Triglycerides/BL; Vitamin E/AD/*BL. .T Postprandial changes in the plasma concentration of alpha- and gamma-tocopherol in human subjects fed a fat-rich meal supplemented with fat-soluble vitamins. .P JOURNAL ARTICLE. .W The plasma concentrations of alpha (alpha)- and gamma (gamma)-tocopherol in 10 male and 15 female subjects (n = 14) received 1 g fat/kg body wt as soybean oil, and the meal was supplemented with 100% of the RDA for fat-soluble vitamins. In expt. 2, the subjects (n = 11) received 1 g fat/kg body wt as 50% soybean oil + 50% cream, and the meal was supplemented with 200% of the RDA for fat-soluble vitamins. The ratio of gamma- :alpha-tocopherol given in the test meal of expt. 1 was 2.8:1 and in expt. 2 was 0.9:1. Blood samples were obtained 0, 3, 6, 9 and 12 h after the meal. Tocopherol concentration was measured in plasma and lipoprotein fractions. In both studies, plasma triglyceride concentration increased significantly after the meal (P less than 0.001). Mean plasma cholesterol and alpha-tocopherol concentrations were unchanged, but plasma gamma-tocopherol concentration was significantly increased at 6, 9 and 12 h after the meal (P less than 0.05). The increase in plasma gamma-tocopherol was due to increases within the triglyceride-rich lipoprotein (TRL) fraction (d less than 1.006 g/ml) at earlier timepoints, followed by a sustained increase within low density lipoprotein (LDL) and high density lipoprotein (HDL) fractions at later timepoints. In contrast, alpha-tocopherol in LDL and HDL decreased postprandially, concomitant with a rise in TRL alpha-tocopherol. Our results are consistent with the concept that there are differences in the distribution of alpha- and gamma-tocopherol in postprandial lipoproteins. .A Meydani M; Cohn JS; Macauley JB; McNamara JR; Blumberg JB; Schaefer EJ. .I 201829 .U 90011389 .S J Nutr 9001; 119(9):1259-68 .M Animal; Cobalt/AD/*PD; Copper/PK/*UR; Drug Interactions; Injections, Intraperitoneal; Injections, Subcutaneous; Kidney/DE/ME; Liver/DE/ME; Male; Penicillamine/PD; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tissue Distribution; Zinc/PK/*UR. .T Trace metal interactions in vivo: inorganic cobalt enhances urinary copper excretion without producing an associated zincuresis in rats. .P JOURNAL ARTICLE. .W The effects of cobalt chloride on copper and zinc metabolism in male Sprague-Dawley rats were examined. These effects were compared with those of penicillamine, a chelating agent utilized in the therapy of the genetic abnormality of copper metabolism in humans, Wilson's disease. Cobalt elicited an increased (approximately 4-fold) urinary excretion of copper lasting through 72 h following a single cobalt dose. In contrast to the marked increase in urinary zinc excretion produced by penicillamine, cobalt greatly reduced (approximately 75%) zinc output in urine. Tissue copper and zinc concentrations were measured after treatment with cobalt at doses ranging from 12 to 60 mg/kg body weight. Substantially reduced (approximately 25%) renal copper concentration was observed at 1 and 3 d after cobalt administration. In addition, cobalt produced a concurrent dose-dependent elevation (up to 1.6-fold) in hepatic zinc concentration. Cytosolic zinc was eluted from a Sephadex G-75 column in the molecular weight region associated with metallothionein. Time-dependent induction of metallothionein concentration (10-fold) in liver by cobalt was confirmed by the cadmium/hemoglobin affinity assay. The ability of inorganic cobalt to elevate zinc concentration in liver and produce increased urinary copper excretion without the zincuresis that normally accompanies penicillamine administration represents a newly defined biological property of this essential trace metal. .A Rosenberg DW; Kappas A. .I 201830 .U 90011390 .S J Nutr 9001; 119(9):1269-86 .M Amino Acids/ME; Animal; Kinetics; Models, Biological/*; Models, Theoretical; Proteins/BI/*ME; Sheep/GD; Support, Non-U.S. Gov't. .T Mathematical integration of protein metabolism in growing lambs. .P JOURNAL ARTICLE. .W A mathematical integration of whole-body protein synthesis and degradation based on protein metabolism in 10 individual tissues in growing lambs is described. The tissues represented are adipose, central nervous system (CNS), gastrointestinal tract (GIT), heart, kidney, liver, muscle, pancreatic and salivary glands (PSG), reticuloendothelial system (RES) and skin, together with a blood pool of amino acids. The fluxes represented in the equations are generally assumed to follow simple or modified mass-action kinetics. The fractional rates for protein synthesis in each tissue were calculated from published values for lambs, where these were available, or alternatively derived using assumptions based on data obtained with rats. The initial protein content of each tissue and the fractional degradation rate were assigned values calculated using data from a slaughter experiment. The model was used to examine whole-body protein synthesis at different rates of growth and to compare the relative contributions of each tissue. The GIT (25-26%) and skin (23-26%) had the highest contributions to total protein synthesis, followed by muscle (21-26%), liver (13-14%), RES (6-7%) and PSG (3-6%), while adipose, CNS, heart and kidney together contributed less than 5%. These values agree reasonably well with experimental values, and thus the model can be used to examine the effect of different growth rates on protein metabolism and its associated energy costs. .A Gill M; France J; Summers M; McBride BW; Milligan LP. .I 201831 .U 90011391 .S J Nutr 9001; 119(9):1287-99 .M Adenosine Triphosphate/*ME; Animal; Energy Metabolism; Models, Biological/*; Models, Theoretical; Potassium/*ME; Proteins/*ME; Sheep/GD; Sodium/*ME; Support, Non-U.S. Gov't. .T Simulation of the energy costs associated with protein turnover and Na+,K+-transport in growing lambs. .P JOURNAL ARTICLE. .W A mathematical representation of the energy-requiring processes of protein turnover and Na+,K+-transport in the tissues of growing lambs is described. This model was then used to examine the relative contributions of these processes to ATP expenditure at two different growth rates (90-230 g/d). Protein turnover accounted for 19% of whole-body ATP expenditure at both growth rates examined, with the gastrointestinal tract (GIT), accounting for 25-27%, muscle for 21-26%, skin for 23-26% and liver for 13% of total protein turnover energy costs. The contribution of Na+,K+-transport increased from 18 to 23% of whole-body heat production as growth rate increased, with the GIT accounting for 39 and 50%, muscle for 17 and 10% and liver for 18 and 23% of total Na+,K+-transport costs at low and high nutrient inputs, respectively. Thus, protein turnover accounted for 19% of the increment in ATP expenditure due to the increased nutrient input at the higher rate of growth, while Na+,K+-transport accounted for 39%, and fat turnover and accretion accounted for 25%, leaving 17% of the ATP increment unaccounted for. .A Gill M; France J; Summers M; McBride BW; Milligan LP. .I 201832 .U 90011392 .S J Nutr 9001; 119(9):1300-3 .M Administration, Oral; Animal; Carbohydrates/AD/*PD; Gastric Inhibitory Polypeptide/*BL; Intestinal Secretions/DE; Mice; Mice, Obese; Radioimmunoassay. .T Stimulation of gastric inhibitory polypeptide release in ob/ob mice by oral administration of sugars and their analogues. .P JOURNAL ARTICLE. .W The effect of oral administration of sugars and their analogues (glucose, galactose, fructose, mannose, sucrose, N-acetylglucosamine, 2-deoxyglucose, 3-O-methylglucose and alpha-methyl-glucoside) on plasma gastric inhibitory polypeptide (GIP) concentration was examined in 18-h fasted ob/ob mice. Administration of sucrose (5.52 mol/kg body wt), or the monosaccharides (11.04 mol/kg body wt) glucose, galactose or fructose, elicited prompt GIP responses that peaked at 30 min. Similar effects were induced by 3-O-methylglucose or alpha-methyl-glucoside, but the stimulatory action of 2-deoxyglucose was delayed. In contrast to the other sugars, N-acetylglucosamine decreased plasma GIP concentration, while mannose exerted no effect. The results suggest that sugars using the Na+ glucose contransporter at the luminal brush border stimulate GIP release without the necessity of being metabolized or removed from the cell by the glucose transporter at the basolateral membrane. The ability of fructose to stimulate GIP release in ob/ob mice suggests that the Na+-glucose contransporter does not represent an exclusive trigger for sugar-induced GIP secretion. .A Flatt PR; Kwasowski P; Bailey CJ. .I 201833 .U 90011393 .S J Nutr 9001; 119(9):1304-10 .M Animal; Comparative Study; Dietary Carbohydrates/PD; Fatty Acids/*BI; Female; Fructose/*PD; Liver/DE/*ME; Rats; Rats, Inbred Strains; Sterols/*BI. .T Comparison among the lipogenic potential of various substrates in rat hepatocytes: the differential effects of fructose-containing diets on hepatic lipogenesis. .P JOURNAL ARTICLE. .W Fructose feeding has been reported to cause hypertriglyceridemia in rats. Apparently this is due to increased hepatic fatty acid synthesis. In hepatocytes from female rats fed a 60% sucrose or fructose diet, the rate of lipogenesis was two times higher than in cells from rats fed a 60% glucose diet and three times higher than in cells from rats fed a commercial nonpurified diet. In hepatocytes from rats fed the fructose-containing diets, lactate was a better substrate than either butyrate or acetate, whereas in cells from rats fed either the glucose diet or the non-purified diet, butyrate was the best lipogenic substrate, and the lipogenic potential of lactate and acetate was similar. In all cases, 1 mM fructose caused a 30-40% stimulation of lipogenesis, while 10 mM glucose did not enhance fat synthesis above the endogenous rates. These results suggest that the differential effect of fructose-containing diets on hepatic lipogenesis results from activation of pyruvate dehydrogenase, thereby increasing the efficiency by which lactate is used as a carbon source for fatty acid synthesis. The differences in lipogenic potential of the various substrates tested is discussed. .A Carmona A; Freedland RA. .I 201834 .U 90011394 .S J Nutr 9001; 119(9):1311-7 .M Animal; Body Weight/DE; Cytotoxicity Tests, Immunologic/MT; Cytotoxicity, Immunologic/*DE; Dietary Fats/*PD; Female; Glycosphingolipids/AN; Immunity, Cellular; Killer Cells, Natural/*ME; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Species Specificity; Spleen/DE; Support, Non-U.S. Gov't. .T Lack of an influence of dietary fat on murine natural killer cell activity. .P JOURNAL ARTICLE. .W The influence of the degree of saturation and the concentration of dietary fat on murine natural killer (NK) cell activity was investigated using C3H/HeN and C57BL/6N mice. Mice were fed purified diets containing either 0% fat (fat free), 5 or 20% safflower oil or 5 or 20% palm oil. Safflower oil and palm oil were used because they are comparable in carbon chain length but vary in the amount of linoleic acid [18:2(n-6)]. Cytotoxicity of splenic NK cells from mice stimulated or unstimulated by the interferon inducer poly I:C was measured against either the YAC-1 lymphoma or line 168 mammary tumor targets. The number of asialo GM1+ cells was not influenced by concentration or degree of saturation of dietary fat. Generally, dietary fat had no consistent influence on NK cell cytotoxicity of spleen cells from either the high responder C3H/HeN mice or the moderate responder C57BL/6N mice against either tumor target. The level of 18:2(n-6) in NK cell-enriched splenic lymphocytes increased with greater levels of dietary safflower oil. Nevertheless, there appeared to be no correlation between lymphocyte fatty acid composition and NK cell cytotoxic capabilities. Therefore, the concentration of dietary safflower or palm oil, and thus 18:2 (n-6), did not appear to effect the number or activity of murine NK cells. .A Erickson KL; Schumacher LA. .I 201835 .U 90011395 .S J Nutr 9001; 119(9):1318-26 .M Adolescence; Adult; Child; China; Glutathione Peroxidase/*BL; Health Status; Hematocrit; Human; Male; Myocardial Diseases/ET/PC; Selenium/BL/*DF/TU; Support, U.S. Gov't, P.H.S.; Vitamin E/BL. .T Biochemical studies of a selenium-deficient population in China: measurement of selenium, glutathione peroxidase and other oxidant defense indices in blood. .P JOURNAL ARTICLE. .W Selenium deficiency is necessary for the development of the cardiomyopathy known as Keshan disease. Healthy boys and men (19-22 per group) from a low selenium area (Dechang County) and from an area where sodium selenite was added to salt (Mianning County) were studied. Keshan disease was endemic in Dechang but occurred rarely in Mianning. After an initial blood sampling, each subject received daily selenium supplements (100 micrograms selenium for boys and 200 micrograms for men) as sodium selenate for 14 d. Blood was sampled again at 7 and 14 d. Boys from Dechang had blood selenium levels similar to levels reported for patients with Keshan disease. Plasma glutathione peroxidase activity in boys and men from Dechang was 33 and 43%, respectively, of values from the corresponding groups in Mianning. Comparison of plasma selenium concentrations in boys and men from Dechang gave values of 33 and 38%, respectively, of the corresponding groups in Mianning. Selenium status did not affect red blood cell superoxide dismutase or catalase activities. Plasma vitamin E concentration was below the normal range in all groups but was unaffected by selenium status. Measurements of plasma malondialdehyde revealed no difference between subjects from Dechang and subjects from Mianning. Selenium supplementation raised plasma glutathione peroxidase activity and plasma selenium concentration in all groups. Groups with higher plasma selenium concentration had relatively smaller increases in glutathione peroxidase activity than in selenium concentration. These results characterize the selenium deficiency in subjects at risk for developing Keshan disease. The results obtained with supplementation of selenium indicate the presence of additional plasma forms of selenium besides glutathione peroxidase. .A Xia YM; Hill KE; Burk RF. .I 201836 .U 90011397 .S J Nutr 9001; 119(9):1333-9 .M Aging/*ME; Animal; Body Composition/DE; Body Weight/DE; Caloric Intake; Comparative Study; Dietary Carbohydrates/AD/*ME/PD; Dietary Fats/ME/PD; Dietary Proteins/ME/PD; Female; Hyperphagia/CI/*ME; Immunity, Natural/DE; Rats; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Resistance to dietary hyperphagia in juvenile rats. .P JOURNAL ARTICLE. .W Adult rats (12 wk of age) fed a wet, high starch diet consumed more energy, gained more weight, and had more carcass fat than rats fed the same diet in a dry form. In contrast, juvenile rats (3.5 wk of age) did not consume more energy, gain more weight, or become fatter when fed the wet, high starch diet than when fed the same diet in dry form. Although rats of both age groups fed high fat diets consumed more energy than rats fed high starch diets, the effect of the high fat diets was much smaller in juvenile than in adult rats. The level of dietary protein (20 vs. 8%) in the diets did not interact with diet type, but juvenile rats fed low protein diets gained less weight than juvenile rats fed standard protein diets. Additional experiments showed that juvenile rats fed a 20% protein diet were capable of increasing fluid intake and energy intake when given sweetened water or insulin, respectively. Thus, low susceptibility to dietary hyperphagia in juvenile rats cannot be explained by assuming that juvenile rats already eat as much as they can. These data are consistent with the possibility that developmental changes in taste responsiveness may contribute to this effect of age. .A Ramirez I. .I 201837 .U 90011398 .S J Nutr 9001; 119(9):1340-7 .M Animal; Blood Volume; Body Weight; Calorimetry, Indirect; Exertion/*; Hemoglobins/AN; Iron/*DF/PH/PK; Iron Radioisotopes/DU; Male; Osmotic Fragility; Oxygen Consumption; Rats; Rats, Inbred Strains. .T Interactions of iron deficiency and exercise training in male Sprague-Dawley rats: ferrokinetics and hematology. .P JOURNAL ARTICLE. .W Ferrokinetic and hematologic studies were performed using adult male Sprague-Dawley rats to determine if 12 wk of exercise training alters the delivery of iron to the red blood cell (RBC) mass, the severity of the anemia or the maximal exercise performance of moderately iron-deficient animals. Forty rats were assigned to either iron-deficient (ID) or control (CN) diets, and further subdivided into sedentary (SD) and exercised (EX) groups. Exercised groups were trained on a treadmill, at a 15% grade, 65% VO2max, for 90 min/d, 4 d/wk. After 12 wk of exercise training and dietary iron deficiency, the final body weight of IDEX rats was 90.5% that of IDSD rats. Fractional plasma iron clearance in IDEX rats was 86% of that in IDSD rats (3.32 vs. 2.85%/min). Exercise training failed to increase absolute VO2max (ml/min) or change hemoglobin concentration in iron-deficient rats. Resting oxygen consumption in IDEX rats was 116% that in IDSD rats (42.8 vs. 32.5 ml.kg-1.min-1, P less than 0.05). We conclude that exercise training and iron deficiency interact to alter iron physiology in exercised, iron-deficient animals. This interaction affects the kinetic behavior of plasma iron, growth and basal oxygen consumption. .A Tobin BW; Beard JL. .I 201838 .U 90011399 .S J Nutr 9001; 119(9):1348-50 .M Abnormalities/*ET; Animal; Biotin/*DF; Female; Maternal-Fetal Exchange; Mice; Pregnancy. .T Is biotin deficiency teratogenic in mice? [letter; comment] .P COMMENT; LETTER. .A Heard GS; Blevins TL. .I 201839 .U 90011415 .S J Gen Intern Med 9001; 4(5):375-83 .M Blood Cells/*AN; Diagnostic Tests, Routine/*; Human; Information Systems; Logistic Models; Medical Records; Prospective Studies; Risk Factors; ROC Curve; Support, U.S. Gov't, P.H.S.; Water-Electrolyte Imbalance/*DI. .T Using clinical data to predict abnormal serum electrolytes and blood cell profiles. .P JOURNAL ARTICLE. .W OBJECTIVE: To identify clinical predictors of five abnormalities on the serum electrolyte panel and two abnormalities on the blood cell profile, to study which data elements carried predictive information, and to measure the predictive accuracy and stability of the resulting predictive equations. DESIGN: Prospective data collection from a computerized medical database supplemented by data entered by physicians who ordered outpatient tests into microcomputers. Equations were derived during an eight-month period and later validated twice in the same setting. SETTING: Academic primary care practice affiliated with a county hospital. PATIENTS AND PARTICIPANTS: Patients were mostly black women; physicians were full-time academic general internists and medical residents. MEASUREMENTS AND MAIN RESULTS: There were 6,570 electrolyte and blood cell profile panels ordered during the equation derivation period. The mean receiver operating characteristic (ROC) curve area for the seven equations was 0.849. For the 4,977 tests ordered during ten months of prospective validation, the mean ROC curve area was only 3% less. For three equations, ROC curve areas were lower for patients with unscheduled visits than for those with scheduled visits (p less than 0.05). Except for two equations involving abnormalities with very low prevalences, the equations were also well calibrated. Prior results for the abnormality being considered were the strongest predictors, followed by other laboratory results, diagnoses, and the physicians' estimate of the probability that the test would be abnormal. CONCLUSIONS: Clinical data can accurately predict abnormal results of common outpatient laboratory tests. Computers can help find the necessary data and produce estimates of risk. .A Tierney WM; Martin DK; Hui SL; McDonald CJ. .I 201840 .U 90011416 .S J Gen Intern Med 9001; 4(5):384-7 .M Ambulatory Care; Curriculum/*; Epidemiology/*ED; Human; Internal Medicine/ED; Internship and Residency/*; Periodicals/*; Teaching/*MT. .T Teaching residents to read the medical literature: a controlled trial of a curriculum in critical appraisal/clinical epidemiology. .P JOURNAL ARTICLE. .W OBJECTIVE: To teach internal medicine residents key principles of clinical epidemiology that are necessary to read critically the medical literature. DESIGN: Two-phase, non-randomized, controlled educational trial. SETTING: University-based training program for residents (PGY-l-PGY-3) in internal medicine. PARTICIPANTS: All 83 residents participated in the trial. Seventy residents completed a test in clinical epidemiology at the end of Phases I and II. INTERVENTIONS: Residents were assigned to one of eight ambulatory care clinics for half a day each week. A literature-based curriculum in critical appraisal was the subject of a weekly pre-clinic conference for four clinics (Group A). The other four clinics (Group B) had a weekly conference on topics in ambulatory care medicine. At the end of Phase I, both groups were given a test of basic knowledge of clinical epidemiology. The curriculum was then modified with the addition of written questions to emphasize important educational points and to stimulate resident participation. The modified curriculum became the subject of the pre-clinic conference for Group B, while Group A changed to topics in ambulatory medicine. At the end of Phase II both groups were again tested on basic knowledge of clinical epidemiology. RESULTS: Group B performed significantly better on the second test than on the first, 68.5% vs. 63.3% (p = 0.034), while Group A did not improve (64.5% vs. 65.9%). The differences in test scores for Test II minus Test I were +5.17% in Group B and -1.44% in Group A (p = 0.019). Twenty-one percent of Group B residents vs. 5% of Group A residents improved their scores by 18% or more. CONCLUSIONS: The residency period is a difficult but important time to teach critical appraisal skills. Educational gains may be small and need to be critically evaluated to stimulate the development of more effective educational programs. .A Kitchens JM; Pfeifer MP. .I 201841 .U 90011419 .S J Gen Intern Med 9001; 4(5):399-402 .M Aged; Boston; Clinical Protocols; Critical Care/*; Female; Hospital Bed Capacity, 300 to 499; Human; Intensive Care Units; Life Support Care/*; Male; Middle Age; Patient Admission; Patient Participation/*SN; Physician-Patient Relations/*; Prospective Studies; Resuscitation/*ST. .T Discussions regarding aggressive care with critically ill patients. .P JOURNAL ARTICLE. .W Protocols concerning orders not to resuscitate have come into existence recently in order to facilitate decisions regarding resuscitation and to ensure that patient's rights to participate in such decisions are preserved. Prior to the do-not-resuscitate (DNR) decision is the decision whether to discuss the issue of resuscitation with the patient at all. To determine how frequently physicians discuss this issue with their patients, the authors gathered information on all 611 patients admitted to the medical intensive care unit (MICU) or the cardiac care unit (CCU) at a tertiary care teaching hospital over a nine-month period. They found that the issue was discussed with only 10.8% of patients or their families on admission of the patients to these units. Such discussions occurred more frequently with older patients, those who were more severely ill or were estimated to have worse prognoses, those with poor intellectual function, and those admitted to the MICU rather than the CCU. .A Blackhall LJ; Cobb J; Moskowitz MA. .I 201842 .U 90011421 .S J Gen Intern Med 9001; 4(5):410-2 .M Colorado; Forms and Records Control/*ST; Hospital Bed Capacity, 300 to 499; Hospitals, Veterans/*; Human; Informed Consent/*; Office Management/*ST; Patients; Reading; Research/*; Support, Non-U.S. Gov't. .T Research consent forms: continued unreadability and increasing length. .P JOURNAL ARTICLE. .W Consent forms are often long and incomprehensible. The authors studied 88 consecutive research consent forms generated at the Denver Veterans Administration Medical Center, evaluating the reading levels of the forms using the Fry Readability Scale and recording the numbers of lines of text. The mean grade reading level required for comprehension was 13.4 years of schooling. Twenty-two percent of all text passages scored were at the postgraduate level of readability. This difficult readability level has not improved since the forms were last tested in 1982. The mean length of the forms was 84.6 lines. Also found was a 58% increase in the length of forms since 1982, a factor known to impair comprehension. These factors, poor readability and increasing length, may make many consent forms incomprehensible. It is recommended that investigators be brief, use plain English, and write consent forms at appropriate reading levels, and receive training on how to obtain valid consent. .A LoVerde ME; Prochazka AV; Byyny RL. .I 201843 .U 90011422 .S J Gen Intern Med 9001; 4(5):413-20 .M Ambulatory Care/*ST; Classification; Communication; Decision Making; Ethics, Medical/*; Human; Malpractice; Patient Participation; Referral and Consultation/ST; Research; Social Responsibility; United States. .T Outpatient clinical ethics. .P JOURNAL ARTICLE. .A Puma JL; Schiedermayer DL. .I 201844 .U 90011423 .S J Gen Intern Med 9001; 4(5):421-31 .M Clinical Competence/*; Curriculum; Human; Internal Medicine/*ED; Internship and Residency/*ST; Interviews; Medical History Taking/*; Physician-Patient Relations/*; Support, U.S. Gov't, Non-P.H.S.; Teaching/MT. .T Residency training in interviewing skills and the psychosocial domain of medical practice [published erratum appears in J Gen Intern Med 1990 Mar-Apr;5(2):169] .P JOURNAL ARTICLE. .A Kern DE; Grayson M; Barker LR; Roca RP; Cole KA; Roter D; Golden AS. .I 201845 .U 90011426 .S J Gen Intern Med 9001; 4(5):453-6 .M Documentation; Forms and Records Control/ST; Human; Language; Medical Records/*ST; Patient Discharge/*; Writing. .T Dictation of the discharge resume: a forgotten link between the spoken and written word [see comments] .P JOURNAL ARTICLE. .W All medical personnel use jargon when conversing about patients. Such jargon can be clarified by questions asked at the moment of discussion. The reader of a discharge summary, however, does not have the option of questioning the author if meanings are ambiguous and vague. Editing discharge summaries is an impossible task--I've tried it and quit, partly from laughing, partly from crying, and mostly because the head record librarian refused to have all the summaries retyped. Save time in the record room by being more concise and clear in your dictation, then use the time you have saved for more rewarding activities. Organize your thoughts, dictate, then go smell the flowers with the recovered time. .A Manning RT. .I 201846 .U 90011427 .S J Gen Intern Med 9001; 4(5):457-9 .M Human; Internship and Residency/*; Periodicals/*; Teaching/*MT. .T Critical appraisal: more work to be done [editorial] .P EDITORIAL. .A Linzer M. .I 201847 .U 90011429 .S J Gen Intern Med 9001; 4(5):461-2 .M Dyspepsia/*DI; Human; Medical History Taking; Physician-Patient Relations. .T A systematic approach to the initial evaluation of dyspepsia [editorial] .P EDITORIAL. .A Kahn KL. .I 201848 .U 90011430 .S J Gen Intern Med 9001; 4(5):463 .M Delivery of Health Care/*; Epidemiology/*; Human. .T Epidemiology, ecolacy, and patient care [editorial] .P EDITORIAL. .A Lipkin M. .I 201849 .U 90011431 .S J Gen Intern Med 9001; 4(5):464 .M Aged; Hearing Tests/*; Human; Mass Screening/*; Middle Age. .T Hearing acuity tests in older adults [letter; comment] .P COMMENT; LETTER. .A Lucas LM. .I 201850 .U 90011432 .S J Gen Intern Med 9001; 4(5):465 .M Female; Human; Hypertension/*; Pregnancy; Pregnancy in Diabetes/*; Pregnancy Complications, Cardiovascular/*. .T Illness in the pregnant patient [letter] .P LETTER. .A Herschberg SN. .I 201851 .U 90011433 .S J Gen Intern Med 9001; 4(5):465-6 .M Fees and Charges/*; Hospitals, Teaching/*EC; Human; Internship and Residency/*. .T Resident involvement in hospital charges [letter; comment] .P COMMENT; LETTER. .A Hillson SD; Rich EC. .I 201852 .U 90011472 .S J Oral Maxillofac Surg 9001; 47(10):1013 .M Dental Implantation/*; General Practice, Dental; Interprofessional Relations/*; Specialties, Dental. .T Implanting the right idea [editorial] [see comments] .P EDITORIAL. .A Laskin DM. .I 201853 .U 90011473 .S J Oral Maxillofac Surg 9001; 47(10):1014-21 .M Adolescence; Adult; Aged; Arthroscopy/MT; Cartilage, Articular/PA/*SU; Dislocations/*SU; Female; Follow-Up Studies; Human; Male; Middle Age; Questionnaires; Retrospective Studies; Temporomandibular Joint Diseases/*SU; Vertical Dimension. .T Retrospective analysis of 100 consecutive surgical arthroscopies of the temporomandibular joint. .P JOURNAL ARTICLE. .W One hundred consecutive surgical arthroscopies of the temporomandibular joint were performed and evaluated with a mean follow-up of 19.4 months. Of the 66 patients, 72.7% had symptoms lasting more than 1 year. The mean postoperative increase in maximal incisal opening was 38.4%. A 7.5% failure rate was noted by objective criteria; 85.7% of the patients rated their postoperative pain and function greatly or moderately improved. All of the respondents stated they would have the arthroscopic surgery again if needed. .A White RD. .I 201854 .U 90011474 .S J Oral Maxillofac Surg 9001; 47(10):1022-5 .M Adult; Arthroscopy/AE; Audiometry; Dislocations/*SU; Female; Hearing Disorders/*ET/PP; Human; Male; Middle Age; Temporomandibular Joint Syndrome/PP/*SU. .T The effect of temporomandibular joint arthroscopy on ear function. .P JOURNAL ARTICLE. .W Many patients with temporomandibular joint (TMJ) dysfunction also complain of subjective symptoms of ear dysfunction. This study was undertaken to evaluate preoperatively patients with ear complaints associated with TMJ pain and dysfunction and to examine the effect of essentially uncomplicated TMJ arthroscopy on subsequent ear function. Fourteen patients (22 joints) were examined arthroscopically. The patients were evaluated by an otologist, and hearing tests were obtained pre- and post-operatively. All patients had normal audiometric studies preoperatively, and these remained unchanged postoperatively. It was concluded that uncomplicated arthroscopy of the TMJ does not cause ear dysfunction. .A Jones JL; Horn KL. .I 201855 .U 90011475 .S J Oral Maxillofac Surg 9001; 47(10):1026-7 .M Arthroscopy/*AE; Hearing Disorders/*ET; Hearing Tests; Human; Temporomandibular Joint Diseases/*SU. .T Preoperative and postoperative audiologic measurements in patients undergoing arthroscopy of the TMJ. .P JOURNAL ARTICLE. .W This article examines the hearing patterns of patients who have undergone arthroscopic surgery using pre- and post-operative pure tone audiometry. Of 29 patients (44 operated joints), one side of one patient showed a decrease of 15 dB immediately postoperatively. On examination there was no apparent anatomic disturbance of the middle or inner ear. The patient regained normal levels of hearing within 2 months. It is concluded that arthroscopic surgery of the TMJ is safe with respect to the middle and inner ear and that it does not affect hearing levels. .A McCain JP; Goldberg HM; de la Rua H. .I 201856 .U 90011476 .S J Oral Maxillofac Surg 9001; 47(10):1028-9 .M Adolescence; Adult; Aged; Female; Greece/EH; Human; Male; Middle Age; Vertical Dimension/*. .T The normal range of mouth opening. .P JOURNAL ARTICLE. .W The maximal mouth opening of 1,160 healthy Greek adults, 18 to 70 years old, was measured. The results were similar to those reported by investigators in other countries. .A Mezitis M; Rallis G; Zachariades N. .I 201857 .U 90011477 .S J Oral Maxillofac Surg 9001; 47(10):1030-6; discussion 1037-8 .M Adult; Bone Transplantation/*; Cartilage/*TR; Dislocations/ET/*SU; Female; Follow-Up Studies; Human; Immobilization; Male; Mandibular Condyle/*IN/SU; Methods; Middle Age; Retrospective Studies; Ribs; Temporomandibular Joint Diseases/*SU; Vertical Dimension. .T Costochondral grafting for posttraumatic temporomandibular joint reconstruction: a review of six cases. .P JOURNAL ARTICLE. .W Costochondral grafting in growing children for missing, diseased, or ankylosed condyles has been widely reported. The use of these grafts for temporomandibular joint (TMJ) reconstruction in nongrowing adults has received relatively little attention. This article reviews the use of costochondral grafts in six cases of posttraumatic TMJ dysfunction in adults. Four patients increased their maximum incisal opening by an average of 49.1%, and two patients showed decreases in opening. Overall clinical results were judged to be very good. It is emphasized that biologic reconstruction of the adult TMJ is preferable to alloplastic reconstruction because, just as in the growing child, the adult articulation must adapt to the demands of the functional matrix. .A Nelson CL; Buttrum JD. .I 201858 .U 90011478 .S J Oral Maxillofac Surg 9001; 47(10):1039-42 .M Adolescence; Adult; Alfentanil/AE/*TU; Anesthesia, Dental/*; Anesthesia, General/*; Human; Jaw/*SU; Mouth/*SU; Questionnaires. .T Alfentanil for general anesthesia in oral and maxillofacial surgery. .P JOURNAL ARTICLE. .W This study evaluated alfentanil (Alfenta, Janssen Pharmaceutica, Piscataway, NJ) as an analgesic supplement to oxygen/nitrous oxide anesthesia for outpatient oral and maxillofacial surgical procedures. Fifty American Society of Anesthesiology (ASA) class I and II patients were induced and maintained with an established regimen. Parameters measured included anesthetic properties, orientation time, recovery time, and presence of side effects. The results indicated that alfentanil provides acceptable anesthesia with minimal recovery time, but occasional side effects such as nausea and vomiting occurred postoperatively. This drug, when properly used, is a welcome addition to other established general anesthetic agents in oral and maxillofacial surgery. .A Edgin WA; Ford ML; Mansfield MJ. .I 201859 .U 90011479 .S J Oral Maxillofac Surg 9001; 47(10):1043-7 .M Alveolar Process/PA/*SU; Animal; Hydroxyapatites/*AE; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't; Tooth/*PA; Tooth Eruption/*. .T Inhibition of tooth eruption through calcium-phosphate ceramic granules in the rat. .P JOURNAL ARTICLE. .W This experiment investigated the reason for disturbances of tooth eruption through hydroxylapatite (HA) granules. HA granules of compact and porous structure were implanted in the pathway of erupting teeth in 14 five-day-old rats. The results demonstrate that the use of this material can result in tooth retention and malformed tooth crowns. Tooth crown malformation can be traced to the formation of ceramo-dentinous complexes which promote bacterial invasion of the pulp cavity, resulting in arrest of the tooth eruption process. .A Holtgrave EA. .I 201860 .U 90011481 .S J Oral Maxillofac Surg 9001; 47(10):1053-61 .M Cephalometry/*MT; Comparative Study; Diagnostic Imaging/*MT; Radiographic Image Enhancement; Skull/*AB/PA; Support, U.S. Gov't, P.H.S.; Tomography, X-Ray Computed. .T A method for three-dimensional image reformation for quantitative cephalometric analysis. .P JOURNAL ARTICLE. .W Recognition and treatment of craniofacial deformities require an understanding of complex skeletal structures in three planes of space. Traditional imaging techniques rely on biplanar radiographs which provide only two-dimensional data. The introduction of three-dimensional image display (3DIR) has provided a method of object analysis in three planes of space, obviating the need for mental reconstruction, and yielding more spatial information than was previously available. This study was undertaken to investigate the quantitative value of three-dimensional images compared with cephalometric techniques in assessing a craniofacial deformity. Metallic marker references were placed on a deformed skull. Measurements taken from cephalograms and three-dimensional images were compared with corresponding digitized and manual measurements taken from the skull. Three-dimensional image reformation provided a more accurate representation of the deformity than the cephalometric methods. Because all structural relationships are preserved in the CT data matrix, measurements are inherently accurate and reproducible. 3DIR offers dynamic advantages over cephalometric methods because data can be manipulated interactively. Further investigation is needed to study the importance of head position and to develop patient selection criteria, scan protocols, and surgical treatment planning algorithms. .A Matteson SR; Bechtold W; Phillips C; Staab EV. .I 201861 .U 90011482 .S J Oral Maxillofac Surg 9001; 47(10):1062-8; discussion 1068-9 .M Adaptation, Physiological; Animal; Bone Plates; Bone Wires; Cephalometry; Female; Immobilization/*; Macaca mulatta; Masticatory Muscles/*PH/SU; Maxilla/*SU; Osteotomy/*MT; Splints/*; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Vertical Dimension. .T Stability of midface augmentation: an experimental study of musculoskeletal interaction and fixation methods. .P JOURNAL ARTICLE. .W This study examined stability of vertical midface augmentation when different methods to alleviate potentially distracting muscles were used. Eighteen adult monkeys underwent Le Fort I osteotomy with interpositional bone grafts. One group had wire fixation of the maxilla and bone graft. A second group underwent a similar procedure with the addition of myotomies of the masseter and temporalis muscles. A third group wore a bite-opening appliance before downgrafting. A fourth group underwent downgrafting with rigid internal fixation. Serial cephalograms with the aid of bone markers were used to assess postsurgical change. The results showed that the animals who underwent rigid fixation had the most stable results, followed by the myotomy and bite-opening appliance groups. The animals who underwent wire fixation with no supplemental procedures had gross relapse, resulting in an average retention of only 15% of the surgical change by 12 weeks. .A Ellis E 3d; Carlson DS; Frydenlund S. .I 201862 .U 90011487 .S J Oral Maxillofac Surg 9001; 47(10):1083-7 .M Adult; Ameloblastoma/CO/PA/*SC; Case Report; Human; Hypercalcemia/*ET; Lung Neoplasms/CO/*SC; Male; Mandibular Neoplasms/*PA. .T Ameloblastoma with metastasis to the lung and associated hypercalcemia. .P JOURNAL ARTICLE. .W A case of ameloblastoma with metastasis to the lung is reported. A rare feature of this case was that the metastasized ameloblastoma was associated with hypercalcemia without osteolytic bone metastasis. .A Harada K; Suda S; Kayano T; Nagura H; Enomoto S. .I 201863 .U 90011488 .S J Oral Maxillofac Surg 9001; 47(10):1087-9 .M Adult; Case Report; Chronic Disease; Female; Fibroma/CO/*RA; Human; Mandibular Neoplasms/CO/*RA; Periapical Diseases/*ET. .T Desmoplastic fibroma of the mandible: a case with an unusual clinical presentation. .P JOURNAL ARTICLE. .W A new case of desmoplastic fibroma of the mandible is reported. The patient was a 29-year-old woman who presented with a 5-year course of abscess-like lesions simulating a chronic apical infection. Radiographically, a nonspecific, small osteolytic area was observed. A wide resection of the tumor and the neighboring bone was performed. .A Valente G; Migliario M; Bianchi SD; Vercellino V. .I 201864 .U 90011489 .S J Oral Maxillofac Surg 9001; 47(10):1090-3 .M Case Report; Cheek; Female; Hemangioma/*PA; Human; Leiomyoma/*PA; Middle Age; Mouth Neoplasms/*PA; Myoma; Neoplasms, Multiple Primary/*; Uterine Neoplasms. .T Angiomyoma of the cheek: a case report. .P JOURNAL ARTICLE. .A Maeda Y; Osaki T. .I 201865 .U 90011490 .S J Oral Maxillofac Surg 9001; 47(10):1093-5 .M Acquired Immunodeficiency Syndrome/*CO; Adult; Case Report; Homosexuality; Human; Male; Oral Hemorrhage/ET; Thrombocytopenia/*ET; Tooth Extraction/AE. .T Immune thrombocytopenia in AIDS patients: case report. .P JOURNAL ARTICLE. .A Maron G; Helmy E; Bays R. .I 201866 .U 90011491 .S J Oral Maxillofac Surg 9001; 47(10):1096-8 .M Case Report; Child; Human; Jaw Cysts/*/RA; Male; Mandibular Condyle/*/RA; Mandibular Diseases/*/RA. .T Simple bone cyst of the mandibular condyle. .P JOURNAL ARTICLE. .A Rubin MM; Murphy FJ. .I 201867 .U 90011493 .S J Oral Maxillofac Surg 9001; 47(10):1102-5 .M Aged; Bone Plates/*; Carcinoma, Squamous Cell/*SU; Case Report; Female; Human; Immobilization/*; Male; Mandible/*SU; Mandibular Neoplasms/*SU; Middle Age; Mouth Neoplasms/*SU; Osteotomy/*MT; Paraganglioma/*SU. .T Small plate osteosynthesis for mandibular reconstruction following osteotomy for tumor resection. .P JOURNAL ARTICLE. .W Cases have been presented that demonstrate the advantages of small plate ostesynthesis in the reconstruction of the mandible following resection of neoplastic disease. Mandibulotomies provide improved access to tumors and thus allow the tumor to be better excised. Prelocalization of the plates allows the precise reconstruction of the mandible following mandibulotomy with minimal morbidity and disturbance of function. .A Postlethwaite KR; Wood GA. .I 201868 .U 90011495 .S J Oral Maxillofac Surg 9001; 47(10):1113-5 .M Bone Transplantation/*MT; Human; Skull/*SU. .T Cranial bone graft harvesting: a modified technique. .P JOURNAL ARTICLE. .A Markowitz NR; Allan PG. .I 201869 .U 90011496 .S J Oral Maxillofac Surg 9001; 47(10):1116-8 .M Cartilage, Articular/SU; Human; Skin Transplantation/*MT; Temporomandibular Joint/SU. .T Dermal graft harvest technique for use in temporomandibular joint disc repair. .P JOURNAL ARTICLE. .A Tucker MR. .I 201870 .U 90011497 .S J Oral Maxillofac Surg 9001; 47(10):1123-4 .M Education, Dental/*ST; Education, Medical/*ST; Human; Surgery, Oral/*ED/TD; United States. .T The double-degree debate continues [letter] .P LETTER. .I 201871 .U 90011498 .S J Oral Maxillofac Surg 9001; 47(10):1124-6 .M Education, Dental/*ST; Education, Medical/*ST; Human; Surgery, Oral/*ED/TD; United States. .T To what degree can we change our future? [letter; comment] .P COMMENT; LETTER. .I 201872 .U 90011499 .S J Oral Maxillofac Surg 9001; 47(10):1126-7 .M Education, Dental, Graduate/*ST; Education, Medical, Graduate/*ST; Human; Interprofessional Relations; Surgery, Oral/*ED; United States. .T To what degree are we maxillofacial surgeons? [letter] .P LETTER. .A Baird W. .I 201873 .U 90011559 .S J Pediatr 9001; 115(4):515-20 .M Environment; Follow-Up Studies; Gestational Age; Human; Infant, Low Birth Weight/*PX; Infant, Newborn; Intelligence/*; Meta-Analysis; Research Design/ST; Social Class. .T Outcome studies of low birth weight infants published in the last decade: a metaanalysis [see comments] .P JOURNAL ARTICLE. .W We conducted a metaanalysis and methods review of 80 studies, published in the last decade, that explored the outcome of low birth weight infants; 27% involved infants whose birth weights were less than or equal to 2500 gm (low birth weight), 44% less than or equal to 1500 gm (very low birth weight), and 29% less than or equal to 1000 gm (extremely low birth weight). Problems found in these studies were grouped into three categories: subject and methods issues, environmental factors, and outcome measurement. The combined average intelligence quotient/developmental quotient (IQ/DQ) of all low birth weight groups was 97.77 (SD 6.19); for control subjects the mean IQ/DQ was 103.78 (SD 8.16). This difference was statistically significant but perhaps not clinically significant. No differences in mean IQ/DQ scores were found among the low birth weight, very low birth weight, and extremely low birth weight subgroups. Statistically significant differences among all groups and control subjects were found when categoric data were analyzed, as were differences among the three subgroups; however, the variety of outcome criteria makes interpretation of the categoric analyses difficult. .A Aylward GP; Pfeiffer SI; Wright A; Verhulst SJ. .I 201874 .U 90011561 .S J Pediatr 9001; 115(4):527-31 .M Centers for Disease Control (U.S.); Convulsions/*ET/GE; Diphtheria-Tetanus-Pertussis Vaccine/*AE; Human; Infant; Poliovirus Vaccine, Oral; Risk Factors; United States. .T Family history of convulsions and use of pertussis vaccine. .P JOURNAL ARTICLE. .W To evaluate the risk of neurologic events after vaccination with diphtheria-tetanus-pertussis (DTP) vaccine, we used data from the Centers for Disease Control Monitoring System for Adverse Events Following Immunization to compare the family history of convulsions in persons reporting neurologic events with that in persons reporting nonneurologic events; these events have an onset within 3 days of immunization with DTP vaccine, given either alone or with oral poliovirus vaccine. Persons reporting neurologic events were 6.4 times more likely to report a prior personal history of convulsions than those reporting nonneurologic events (95% confidence interval 4.7 to 8.8), and were 2.4 times more likely to report a history of convulsions in first-degree family members, that is, siblings or parents (95% confidence interval 1.7 to 3.4). Similar risks were noted for subgroup analyses controlling for type of event (febrile vs nonfebrile convulsion), age at immunization, source of report, number of previous doses of DTP vaccine, and day of onset. Because the Centers for Disease Control monitoring system receives reports on a nonrandom sample of all adverse events after immunization, selection bias could not be ruled out. On the basis of these data, we conclude that children with a family history of seizures are at increased risk of neurologic events, primarily febrile convulsions, after DTP vaccination. However, this increase in risk may reflect a nonspecific familial tendency for convulsions rather than a specific vaccine effect. Considering the rare occurrence of neurologic events after DTP vaccination, the generally benign outcome of febrile convulsions (which make up the majority of these neurologic events), and the possible increased risk of pertussis in the general population if the estimated 5% to 7% of persons with a first-degree family history of convulsions were exempted from pertussis vaccination, we further conclude that a history of convulsions in siblings or parents should not be a contraindication to pertussis vaccination. Special care in the prevention of postvaccination fever may be warranted in children with a family history of seizures. .A Livengood JR; Mullen JR; White JW; Brink EW; Orenstein WA. .I 201875 .U 90011562 .S J Pediatr 9001; 115(4):532-6 .M Child; Convulsions/EP/*ET; Female; Human; Hypertension/CO; Kidney Failure, Chronic/*CO/SU; Kidney Transplantation/*AE; Male; Ohio; Prognosis; Retrospective Studies. .T Convulsions in children undergoing renal transplantation. .P JOURNAL ARTICLE. .W We reviewed the records of 154 children who received 207 renal transplants for end-stage renal disease from 1965 to 1987, and discovered that 48 (31%) had had convulsive seizures, some before transplant surgery, others only after transplant, and some during both before and after transplantation. The majority of children had minimal long-term problems, and 60% of the children had only a single convulsion. In six of the patients, convulsions were a manifestation of more serious underlying conditions that produced significant morbidity. Seizures of differing clinical type occurred, with hypertension being the most significant etiologic factor. In children with renal failure, there are minimal symptoms heralding the hypertensive encephalopathy. Rapid resolution without recurrence of seizures after control of hypertension is a major sign that hypertension was the cause and that the long-term prognosis is good. .A McEnery PT; Nathan J; Bates SR; Daniels SR. .I 201876 .U 90011563 .S J Pediatr 9001; 115(4):537-44 .M Adolescence; Age Factors; Child; Circadian Rhythm/*; Eating; Female; Human; Insulin-Like Growth Factor I/AN; Male; Puberty; Sex Factors; Sleep/PH; Somatotropin/BL/*SE; Support, U.S. Gov't, P.H.S.. .T Growth hormone secretory dynamics in subjects with normal stature. .P JOURNAL ARTICLE. .W To evaluate the dynamics of growth hormone (GH) secretion in subjects with normal stature and to determine whether a correlation exists between height and the quantity of GH secreted, we determined the 24-hour GH concentration by measuring GH levels every 30 minutes in 27 boys and 19 girls of normal height, 7 to 18 years of age, of whom 24 were prepubertal and 22 in various stages of puberty. Spontaneous GH secretion had wide variations, with values ranging from less than 1.0 to 67.0 micrograms/L. In prepubertal children the highest GH levels were usually noted during sleep; in pubertal subjects the highest values were distributed almost equally between sleep and wake hours. In all subjects, GH secretion appeared to decrease before meals, followed by an increase after meals. Most indexes of GH secretion and insulin-like growth factor I levels were significantly greater in pubertal than in prepubertal subjects (p less than 0.002), and in both groups the GH concentration was significantly greater during sleep (p less than 0.005). In all groups the 24-hour GH concentration correlated significantly with the area under the GH curve, 24-hour GH pulse amplitude, and GH concentration and peak GH level during sleep and wake hours (P less than 0.0001); 24-hour GH concentrations correlated with insulin-like growth factor I levels only when the entire group of 46 subjects was considered (p less than 0.01). There were no significant correlations between 24-hour GH concentration and the subjects' age, bone age, height (SD score), weight (SD score), or body mass index. We conclude that in subjects with normal stature, mean 24-hour GH concentrations vary considerably and in the low range overlap with values reported in hypopituitarism. .A Costin G; Kaufman FR; Brasel JA. .I 201877 .U 90011565 .S J Pediatr 9001; 115(4):549-53 .M Ductus Arteriosus, Patent/*SU; Heart Catheterization; Human; Infant; Prosthesis/*; Pulmonary Artery/SU. .T Transcatheter closure of patent ductus arteriosus in pediatric patients. .P JOURNAL ARTICLE. .W A "double disk" occlusion device (Rashkind PDA occluder system) has been designed to allow transcatheter closure of patent ductus arteriosus (PDA). During a 3-year period, we examined 37 infants and children (not premature neonates) with PDA as their only significant cardiovascular defect. Seventy-eight percent of these patients were considered potential candidates for the use of the PDA occlusion device, and it was successfully placed in all but 2 of 27 patients who underwent cardiac catheterization (PDA too small in one and too large in one). Only one of the remaining 25 patients had a significant residual shunt after placement of the device, which therefore was removed in the catheterization laboratory before surgical ligation of the PDA. There was no clinical evidence of a residual PDA in any patient. The duration of hospitalization was less than 24 hours for each of the last 20 procedures. Echocardiography demonstrated return to normal chamber dimensions in all patients, but a tiny, clinically undetectable residual leak around the device was found in three patients by Doppler evaluation. The transcatheter procedure was preferred over surgery by more than 90% of families and can be completed with a much shorter hospitalization than surgical ligation. We conclude that transcatheter closure of patent ductus arteriosus is feasible in the majority of children with PDA. .A Latson LA; Hofschire PJ; Kugler JD; Cheatham JP; Gumbiner CH; Danford DA. .I 201878 .U 90011566 .S J Pediatr 9001; 115(4):554-60 .M Adolescence; Cardiac Output/*; Child; Child, Preschool; Comparative Study; Echocardiography, Doppler/*; Female; Heart Catheterization; Human; Infant; Male; Pulmonary Artery; Thermodilution/*. .T A comparison of thermodilution and pulsed Doppler cardiac output measurement in critically ill children [see comments] .P JOURNAL ARTICLE. .W To evaluate the pulsed Doppler cardiac output method as a noninvasive means for determining cardiac output in critically ill children, we performed paired pulsed Doppler and thermodilution cardiac output determinations in 17 critically ill children. Commercially available equipment, specifically designed for this purpose, was employed. Forty paired thermodilution and pulsed Doppler determinations were made. There was a significant correlation between the two measurements (pulsed Doppler = 0.84 thermodilution + 0.39; r = 0.79, p less than 0.01). The ranges of thermodilution measurements (1.02 to 6.26 L/min; median 2.77 L/min) and pulsed Doppler measurements (1.13 to 6.35 L/min; median 2.57 L/min) were not different (p = 0.25). However, differences between individual paired thermodilution and pulsed Doppler measurements were large (-3.13 to 2.03 L/min; median 0.12 L/min), and the percentage difference between individual paired thermodilution and pulsed Doppler measurements ranged from 0.41% to 102.5% (median 12.7%). A discrepancy of 15% or more between thermodilution and pulsed Doppler was encountered in 18 (45%) of 40 of paired measurements (95% confidence interval: 29% to 61%), and one fourth of the paired measurements differed by more than 25%. We conclude that, as employed in this study, pulsed Doppler cardiac output determination is not sufficiently representative of the thermodilution output to be employed for hemodynamic monitoring in critically ill children. .A Notterman DA; Castello FV; Steinberg C; Greenwald BM; O'Loughlin JE; Gold JP. .I 201879 .U 90011567 .S J Pediatr 9001; 115(4):561-7 .M Adolescence; Adult; Amphotericin B/TU; Antibiotics/TU; Biopsy; Bronchoscopy/*; Child; Child, Preschool; Human; Irrigation; Lung Diseases/*DI/ET; Neoplasms/*CO; Pneumonia, Pneumocystis carinii/DI; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Role of flexible bronchoscopy in the diagnosis of pulmonary infiltrates in pediatric patients with cancer. .P JOURNAL ARTICLE. .W We reviewed 60 consecutive flexible bronchoscopies done during a 36-month period in 48 pediatric cancer patients with undiagnosed pulmonary infiltrates. Diagnostic procedures during bronchoscopy included 40 brushings, 50 bronchoalveolar lavages, and 6 transbronchial and mucosal biopsies. A total of 16 specific diagnoses were made by bronchoscopy (27% diagnostic yield), including infection (12), pulmonary leukemia (3), and lymphoma (1). The largest proportion of specific diagnoses came from lavage (14/50) and the smallest from brushings (1/40). Biopsies were also useful for selected patients. The low overall yield for bronchoscopy was probably due to the routine use of empiric broad-spectrum antibiotics and antifungal therapy, as well as trimethoprim-sulfamethoxazole prophylaxis for Pneumocystis carinii pneumonitis. Subsequent specific diagnoses were obtained by other procedures (open biopsy, needle aspiration, or autopsy) for 10 patients with negative bronchoscopy results and 3 patients with diagnostic bronchoscopies. These additional diagnoses included 7 infections (Pneumocystis carinii (1), Candida tropicalis (1), cytomegalovirus (1), and Aspergillus (4), and 6 other diagnoses with nonspecific histologic findings. A positive bronchoscopy result may be useful, but negative bronchoscopy findings do not justify delaying other diagnostic procedures or discontinuing antibiotic and antifungal therapy in children with cancer and pulmonary infiltrates. .A Stokes DC; Shenep JL; Parham D; Bozeman PM; Marienchek W; Mackert PW. .I 201880 .U 90011568 .S J Pediatr 9001; 115(4):568-72 .M Adolescence; Anemia, Sickle Cell/CO/PP/*TH; Blood Transfusion/*; Child; Erythrocytes/*TR; Erythrocytes, Abnormal/AN; Female; Hemoglobin, Sickle/AN; Human; Male; Spleen/*PP/RI; Splenic Infarction/ET; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Technetium Tc 99m Sulfur Colloid/DU. .T Splenic phagocytic function in children with sickle cell anemia receiving long-term hypertransfusion therapy. .P JOURNAL ARTICLE. .W To determine the effects of blood transfusions on splenic function in older patients with sickle cell anemia, we investigated splenic function in 12 patients who had had cerebrovascular accidents and who were being treated at two collaborating centers using different transfusion protocols. Splenic function was assessed by radionuclide scan and pocked erythrocyte count. Patients were 6 to 18 years of age and had been receiving transfusions for 7 months to 10 years (median 4.2 years). Of the 12 children, five had normal or increased splenic size and function (normal scan and normal or minimally elevated pocked erythrocyte count). All were receiving intensive transfusion therapy, with the aim of maintaining the hemoglobin S level at less than 20%. The other seven patients had abnormal splenic function (absent radionuclide uptake and elevated pocked erythrocyte count); each was receiving less intensive transfusion therapy, with the pretransfusion hemoglobin S level usually at 30% to 40%. No patient developed bacterial septicemia while receiving hypertransfusion therapy. We conclude that splenic function during a long-term transfusion program is variable, depending in part on the "intensity" of transfusion therapy. Apparent splenic involution and fibrosis may be a reversible event in some patients. .A Buchanan GR; McKie V; Jackson EA; Vedro DA; Hamner S; Holtkamp CA. .I 201881 .U 90011569 .S J Pediatr 9001; 115(4):573-6 .M Adolescence; Apnea/ET; Arnold-Chiari Deformity/CO/DI/*SU; Child; Child, Preschool; Decompression; Female; Human; Infant; Infant, Newborn; Magnetic Resonance Imaging; Male; Scoliosis/ET; Skull/*SU. .T Chiari type I malformation in children. .P JOURNAL ARTICLE. .W We reviewed the recent experience at Texas Children's Hospital by examining the records of 11 children who underwent suboccipital decompression for symptomatic Chiari type I malformation. Presenting complaints included neck pain (1 child), scoliosis (4 children), back pain (1 child), torticollis (1), motor dysfunction (1), and apnea (3 children). Neurologic findings were normal in 7 of the 11 children. The craniocervical junction and medulla were studied by magnetic resonance imaging, which revealed anatomy consistent with Chiari type I malformation in all cases. At surgery, all patients had tonsillar herniation to the first cervical vertebra or below. Three patients had syringomyelia. Postoperatively, either the patients were symptom free or, in the cases of scoliosis and torticollis, there was no progression. Our experience suggests that Chiari type I malformation may occur in childhood with varied and unusual clinical findings. Magnetic resonance imaging was essential to the diagnosis; the presence of tonsillar herniation was confirmed at surgery. The results of suboccipital decompression were favorable in this series. .A Dure LS; Percy AK; Cheek WR; Laurent JP. .I 201882 .U 90011570 .S J Pediatr 9001; 115(4):577-82 .M Acetylcarnitine/UR; Carnitine/AA/*AN/*TU/UR; Case Report; Child; Child, Preschool; Chromatography, High Pressure Liquid; Fasting/PH; Fatty Acid Desaturases; Human; Infant; Male; Support, U.S. Gov't, P.H.S.. .T Quantitation of urinary carnitine esters in a patient with medium-chain acyl-coenzyme A dehydrogenase deficiency: effect of metabolic state and L-carnitine therapy. .P JOURNAL ARTICLE. .W Urinary carnitine esters were quantitated in an infant with medium-chain acylcoenzyme A dehydrogenase deficiency by means of a highly sensitive and specific radioisotopic exchange high-pressure liquid chromatography method. During fasting, the excretion of free carnitine and of acetylcarnitine, octanoylcarnitine, and hexanoylcarnitine was increased. The fractional tubular reabsorption of free carnitine was decreased, suggesting a renal leak of free carnitine. In the symptom-free, fed state, only minor amounts of free carnitine and of short-chain acylcarnitine, octanoylcarnitine, and hexanoylcarnitine were present in urine, and carnitine loss occurred in the form of "other" carnitine esters not exceeding that of control subjects. During L-carnitine therapy, the excretion of free carnitine, short-chain acylcarnitine, octanoylcarnitine, and hexanoylcarnitine, and particularly of "other" carnitine esters, was increased, suggesting a possible detoxifying effect of administered carnitine that is not confined to the elimination of octanoic and hexanoic acids. The employed method detects very low urinary concentrations of octanoylcarnitine and hexanoylcarnitine (less than 1 mumol/L) characteristic of medium-chain acyl-coenzyme A dehydrogenase deficiency and may be useful in screening for this disease, which has been associated with sudden infant death. .A Schmidt-Sommerfeld E; Penn D; Kerner J; Bieber LL; Rossi TM; Lebenthal E. .I 201883 .U 90011571 .S J Pediatr 9001; 115(4):583-4 .M Animal; Colic/*ET; Food Hypersensitivity/*CO; Human; Infant, Newborn; Milk/AE; Research Design. .T Infantile colic and food allergy: fact or fiction? [editorial] .P EDITORIAL. .A Sampson HA. .I 201884 .U 90011572 .S J Pediatr 9001; 115(4):585-7 .M Child; Female; Growth Disorders/*DI/DT; Human; Male; Somatotropin/*DF/TU. .T How should we test for growth hormone deficiency, and whom should we treat? [editorial] .P EDITORIAL. .A Lippe B; Frasier SD. .I 201885 .U 90011573 .S J Pediatr 9001; 115(4):589-92 .M Acquired Immunodeficiency Syndrome/*CO; Case Report; Child; Christmas Disease/CO; Diphtheria-Tetanus-Pertussis Vaccine/*; Human; Male; Whooping Cough/*CO/DI. .T Pertussis in a previously immunized child with human immunodeficiency virus infection. .P JOURNAL ARTICLE. .A Adamson PC; Wu TC; Meade BD; Rubin M; Manclark CR; Pizzo PA. .I 201886 .U 90011574 .S J Pediatr 9001; 115(4):592-4 .M Breath Tests; Colic/*PP; Colon/*PP; Crying; Female; Human; Hydrogen/*AN; Infant; Male; Support, Non-U.S. Gov't. .T Colonic hydrogen production in infants with colic [see comments] .P JOURNAL ARTICLE. .A Hyams JS; Geertsma MA; Etienne NL; Treem WR. .I 201887 .U 90011575 .S J Pediatr 9001; 115(4):595-8 .M Alanine/DU; Ammonia/BL; Argininosuccinate Lyase/*DF; Argininosuccinate Synthetase/*DF; Carbamyl Phosphate Synthase (Ammonia)/*DF; False Positive Reactions; Heterozygote Detection/*; Human; Ligases/*DF; Lyases/*DF; Ornithine Carbamoyltransferase/*DF; Orotic Acid/UR; Proteins/DU; Support, U.S. Gov't, P.H.S.. .T False positive alanine tolerance test results in heterozygote detection of urea cycle disorders. .P JOURNAL ARTICLE. .A Batshaw ML; Naylor EW; Thomas GH. .I 201888 .U 90011576 .S J Pediatr 9001; 115(4):598-600 .M Adolescence; Body Height/*DE; Child; Child, Preschool; Female; Follow-Up Studies; Human; Hypoglycemia/*ET; Infant; Infant, Newborn; Male; Somatotropin/*DF/TU. .T Long-term growth of children with growth hormone deficiency and hypoglycemia. Therapeutic Trial of Growth Hormone Committee. Medical Research Council of Canada. .P JOURNAL ARTICLE. .A Dean HJ; Friesen HG. .I 201889 .U 90011577 .S J Pediatr 9001; 115(4):600-3 .M Brain/*PA; Case Report; Female; Human; Hypothyroidism/DI/DT/*PA; Infant; Magnetic Resonance Imaging; Thyroxine/TU. .T Changes in brain maturation detected by magnetic resonance imaging in congenital hypothyroidism [see comments] .P JOURNAL ARTICLE. .A Alves C; Eidson M; Engle H; Sheldon J; Cleveland WW. .I 201890 .U 90011578 .S J Pediatr 9001; 115(4):603-5 .M Case Report; Duodenal Obstruction/*CN; Female; Human; Infant, Newborn; Intestinal Atresia/*CO; Lipomatosis/CO/DT/*RA; Pancreatic Diseases/CO/DT/*RA; Pancreatic Extracts/TU; Tomography, X-Ray Computed. .T Pancreatic lipomatosis and duodenal stenosis or atresia in children. .P JOURNAL ARTICLE. .A Dupont C; Sellier N; Chochillon C; Gobert JG; Helardot PG; Kalifa G. .I 201891 .U 90011579 .S J Pediatr 9001; 115(4):605-8 .M Adult; Alanine/*DU; Allopurinol/DU; Ammonia/BL; Case Report; False Positive Reactions; Female; Heterozygote Detection/*; Human; Infant, Newborn; Male; Ornithine Carbamoyltransferase/*DF; Pedigree; Support, Non-U.S. Gov't; Uridine/UR. .T False positive results from the alanine loading test for ornithine carbamoyltransferase deficiency heterozygosity. .P JOURNAL ARTICLE. .A MacKenzie AE; MacLeod HL; Heick HM; Korneluk RG. .I 201892 .U 90011580 .S J Pediatr 9001; 115(4):609-11 .M Antibody Formation; Hepatitis Antibodies/*IM; Hepatitis B/*IM/PC; Human; Infant, Newborn; Viral Hepatitis Vaccines/TU. .T Poor IgM antibody response to hepatitis B core antigen in infants with hepatitis B virus infection. .P JOURNAL ARTICLE. .A Margolis HS; Xu ZY; Nainan OV; Ou-Yang PY; Duan SC; Zhuang YL. .I 201893 .U 90011581 .S J Pediatr 9001; 115(4):611-4 .M Carnitine/*DF/TU; Diseases in Twins/*; Female; Human; Infant, Newborn; Ornithine Carbamoyltransferase/*DF; Pregnancy; Pregnancy Complications/*; Support, Non-U.S. Gov't. .T Secondary carnitine deficiency in the newborn period in twins of a mother with partial ornithine transcarbamylase deficiency. .P JOURNAL ARTICLE. .A Nagao M; Tsuchiyama A; Aoyama T; Mori T; Oyanagi K. .I 201894 .U 90011583 .S J Pediatr 9001; 115(4):621-4 .M Catheters, Indwelling; Extracorporeal Membrane Oxygenation/*AE; Human; Infant, Newborn; Infarction/ET; Microscopy, Electron, Scanning; Polyvinyl Chloride; Thromboembolism/*ET. .T Bypass circuits as the source of thromboemboli during extracorporeal membrane oxygenation. .P JOURNAL ARTICLE. .W To determine the presence and extent of thrombus formation in the apparatus used for extracorporeal membrane oxygenation we studied various portions of the polyvinylchloride circuit from five infants who received extracorporeal membrane oxygenation for 70 to 330 hours. All infants had right-sided cannulation. Sections were cut from the circuit at the time of decannulation and subjected to light and scanning electron microscopy. The site that contained the most thrombus formation was the membrane oxygenator bypass circuit, which is subjected to repeated periods of unclamping and clamping to direct blood flow through the membrane oxygenator. Autopsy results from nonsurvivors showed evidence of pulmonary and renal infarcts, a left frontal lobe infarct, a thromboembolus of the left external and internal carotid arteries, and thrombi in the lungs, kidney, brain, and coronary arteries. One survivor had computed tomographic evidence of infarction of the left middle cerebral artery distribution. We suggest that the areas of the extracorporeal membrane oxygenation circuit subjected to repeated changes in flow dynamics may be the source of microemboli. .A Fink SM; Bockman DE; Howell CG; Falls DG; Kanto WP Jr. .I 201895 .U 90011584 .S J Pediatr 9001; 115(4):625-30 .M Exchange Transfusion, Whole Blood; Extracorporeal Membrane Oxygenation/*AE; Fibrin Fibrinogen Degradation Products/AN; Fibrinogen/AN; Hemoglobins/AN; Hemolysis/*; Heparin/TU; Human; Infant, Newborn. .T Hemolysis during long-term extracorporeal membrane oxygenation. .P JOURNAL ARTICLE. .W We studied the cause of hemolysis during extracorporeal membrane oxygenation (ECMO) by monitoring hematologic and coagulation profiles in seven consecutive infants treated with this procedure. A constrained vortex pump was used in all patients, and the average duration of ECMO was 224 +/- 111 (SD) hours. In all patients, plasma free hemoglobin was low during the first 48 hours after the initiation of ECMO. Later, when visible clots appeared in the ECMO circuit, plasma hemoglobin progressively rose. A rise in the level of fibrin degradation products and a fall in the fibrinogen level were observed concurrently with a rise in the plasma hemoglobin level. After complete circuit changes in six patients, plasma free hemoglobin, fibrin split products, and fibrinogen all returned to baseline values. Neither circuit component changes nor exchange transfusion was effective in normalizing the levels of plasma free hemoglobin, fibrin split products, and fibrinogen. We conclude that when ECMO is administered for prolonged periods, circuit thrombosis occurs and hemolysis ensues. Additional studies are needed to assess the contribution of the constrained vortex pump to this process. .A Steinhorn RH; Isham-Schopf B; Smith C; Green TP. .I 201896 .U 90011588 .S J Pediatr 9001; 115(4):652-6 .M Alkaline Phosphatase/BL; Blood Proteins/AN; Blood Urea Nitrogen; Caloric Intake; Caseins/*PD; Double-Blind Method; Human; Hydrogen-Ion Concentration; Infant Food/*; Infant, Low Birth Weight/GD/ME; Infant, Newborn; Infant, Premature/*GD/ME; Milk Proteins/*PD; Prealbumin/AN; Random Allocation; Support, Non-U.S. Gov't. .T Growth and metabolic response of premature infants fed whey- or casein-dominant formulas after hospital discharge. .P JOURNAL ARTICLE. .W We conducted a double-blind, randomized study to test the hypothesis that a whey-dominant formula permits a growth and metabolic advantage over a casein-dominant formula in preterm infants after hospital discharge. Nineteen low birth weight infants were studied for 6 months from the time of discharge. Ten received a casein-dominant formula, and nine received a whey-dominant formula. Growth (weight, length, head circumference, mid-arm circumference, and skin-fold thickness), biochemical measurements (alkaline phosphatase activity, acid-base status, and hemoglobin, serum total protein, albumin, and urea nitrogen levels), and quantity of formula intake did not differ significantly between the groups over a 6-month study period. Serum transthyretin and urea nitrogen concentrations differed significantly between the two feeding groups at the day of entry into the study only. The results indicate that, after hospital discharge, premature infants fed a whey-dominant formula do not differ in growth or biochemical measurements from those fed a casein-dominant formula. .A Bernbaum JC; Sasanow SR; Churella HR; Daft A. .I 201897 .U 90011589 .S J Pediatr 9001; 115(4):657 .M Breast Feeding/*; Female; Human; Infant; Rickets/*PC; Vitamin D/*TU. .T Vitamin D and the breast-fed baby [letter] .P LETTER. .A Forbes GB. .I 201898 .U 90011590 .S J Pediatr 9001; 115(4):657-8 .M Acquired Immunodeficiency Syndrome/*TM; Child, Preschool; Female; Follow-Up Studies; Human; Infant; Pregnancy; Pregnancy Complications, Infectious/*. .T Risk of vertical transmission of human immunodeficiency virus infection [letter] .P LETTER. .A Tuset C; Tuset L; Garcia-Zarco M; Leon P; Elorza JF; Palomar EF. .I 201899 .U 90011593 .S J Pediatr 9001; 115(4):660-1 .M Bromates/*PO; Bromine/*PO; Hemodialysis; Human; Peritoneal Dialysis/*. .T Treatment of bromate poisoning [letter; comment] .P COMMENT; LETTER. .A Warshaw BL. .I 201900 .U 90011594 .S J Pediatr 9001; 115(4):661-3 .M Antineoplastic Agents/*AE; Biopterin/*AA/TU; Dihydropteridine Reductase/*DF; Human; Leukemia, Lymphocytic, Acute/DT; NADH, NADPH Oxidoreductases/*DF; Phenylalanine/*BL. .T Hyperphenylalaninemia caused by dihydropteridine reductase deficiency in children receiving chemotherapy for acute lymphoblastic leukemia [letter] .P LETTER. .A Blau N; Curtius AC; Kierat L; Leupold D; Kohne E. .I 201901 .U 90011595 .S J Pediatr 9001; 115(4):663-4 .M Circumcision/*; Human; Infant, Newborn; Male; Penile Diseases/PC; Urinary Tract Infections/*PC. .T The foreskin and urinary tract infections [letter] .P LETTER. .A Schoen EJ. .I 201902 .U 90011745 .S J Acquir Immune Defic Syndr 9001; 2(5):421-5 .M AIDS Serodiagnosis/*/PX; Human; HIV Infections/*DI/PX/TH; Time Factors. .T HIV infection as a disease: the medical indications for early diagnosis [editorial] .P EDITORIAL. .A Volberding P. .I 201903 .U 90011751 .S J Acquir Immune Defic Syndr 9001; 2(5):469-71 .M Autoantibodies/*AN; AIDS Dementia Complex/*IM; Brain/*IM; Human; Molecular Weight; Support, U.S. Gov't, P.H.S.. .T Brain-reactive antibodies and the AIDS dementia complex. .P JOURNAL ARTICLE. .W To determine the role of autoantibodies in the development of the AIDS dementia complex, brain-reactive antibodies (BRAs) were assayed in 30 sera samples obtained from AIDS patients. Eighteen samples were obtained from AIDS patients with neuropsychological complications, and 12 samples were obtained from patients without any neuropsychological involvement. BRAs were analyzed using strips of nitrocellulose electroblots as a source of antigen, and were prepared from a sample of normal human parahippocampal tissue subjected to SDS-PAGE. Fourteen of 18 patients with neuropsychological complications and 4 of 12 patients without such complications were positive for BRAs to a protein with Mr of 45,000-50,000. .A Kumar M; Resnick L; Loewenstein DA; Berger J; Eisdorfer C. .I 201904 .U 90011752 .S J Acquir Immune Defic Syndr 9001; 2(5):472-80 .M Acquired Immunodeficiency Syndrome/EP; Epidemiologic Methods; Human; HIV Seroprevalence/*; Prevalence; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; United States. .T Estimating prevalence of HIV infection: considerations in the design and analysis of a national seroprevalence survey. .P JOURNAL ARTICLE. .W A national survey to estimate prevalence of HIV infection would provide a useful addition to available information about the current status and future prospects of the AIDS epidemic in the United States. Both design and interpretation of a prevalence study should make use of existing information about the biology and epidemiology of AIDS. In conjunction with such information, a survey would help increase the accuracy of prevalence estimates and aid in making projections, despite the possibility that participation rates will differ in infected and uninfected individuals. .A De Gruttola V; Fineberg HV. .I 201905 .U 90011753 .S J Acquir Immune Defic Syndr 9001; 2(5):481-5 .M Adolescence; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Comparative Study; Female; Human; HIV Antibodies/*AN; HIV Seroprevalence; HTLV-I Antibodies/*AN; Infant; Ivory Coast; Male; Middle Age; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Prevalence of HTLV-I compared to HIV-1 and HIV-2 antibodies in different groups in the Ivory Coast (West Africa) [published erratum appears in J Acquir Immune Defic Syndr 1990;3(5):550] .P JOURNAL ARTICLE. .W Different Ivorian population groups were comparatively tested for antibodies to HTLV-1, HIV-1, and HIV-2. They included 1,334 healthy individuals, 176 unselected medical patients in regional hospitals, 149 female prostitutes, and 65 males with a sexually transmitted disease (STD) collected in 1987 from four regions (east, north, west, and central). The HTLV-1 prevalence averaged 1 to 2.7% in the different regions, without significant increase in sexually overexposed groups. Furthermore, in Dabou Protestant Hospital, 60 km west of Abidjan, 414 blood donors, 109 asymptomatic HIV-positive individuals, and 181 AIDS clinical cases were also tested. While a significant increase in the prevalence of HTLV-1 antibodies was observed only in AIDS patients. HIV-1 and HIV-2 prevalence increased, as expected, from a low rate (2.4%) in the general population to an intermediate rate (13-15%) in blood donors and unselected hospitalized patients and to a high rate (35%) in prostitutes and STD male patients. .A Ouattara SA; Gody M; de-The G. .I 201906 .U 90011755 .S J Acquir Immune Defic Syndr 9001; 2(5):497-502 .M Adolescence; Adult; Age Factors; Aged; Female; Human; Middle Age; Racial Stocks; Sex Behavior; Sexual Partners/*; United States. .T Trends in the number of sexual partners among American women. .P JOURNAL ARTICLE. .W Data provided by 797 women were analyzed to determine how sexual behavior has changed over time. These women, interviewed in 1983, were originally enrolled as healthy controls for a cervical cancer study. A total of 54.5% of white women and 15.6% of black women had no partners other than their husbands. White women less than 35 years old had twice as many sexual partners during their lifetime (mean of 5.5) as white women greater than or equal to 55 years old (mean of 2.8). Among women greater than or equal to 40 years old, black women had more sexual partners than white women, but among younger women there was little difference by race. Although the number of sexual partners was low compared to homosexual men of the same period, the trends among young women (born 1944 to 1963) to have a higher number of partners and younger ages at the time of first sexual experience indicate that sexual behavior changed in ways that might promote the spread of AIDS and other venereal diseases among women. .A Biggar RJ; Brinton LA; Rosenthal MD. .I 201907 .U 90011756 .S J Acquir Immune Defic Syndr 9001; 2(5):503-13 .M Acquired Immunodeficiency Syndrome/EH/EP/*ET; Adult; Blacks; Connecticut/EP; Cross-Sectional Studies; Ethnic Groups/*; Female; Hispanic Americans; Human; HIV Seropositivity/EP; Male; Multivariate Analysis; Racial Stocks/*; Risk Factors; Substance Abuse, Intravenous/*CO; Support, U.S. Gov't, P.H.S.. .T Race/ethnicity as a risk factor for HIV-1 infection among Connecticut intravenous drug users. .P JOURNAL ARTICLE. .W This cross-sectional study of 341 entrants to drug abuse treatment in four Connecticut cities in 1986-1987 evaluated whether demographic, behavioral, viral serologic, or economic differences explained the disproportionate risk of human immunodeficiency virus type 1 (HIV-1) infection among black and Hispanic intravenous drug users (IVDUs), relative to non-Hispanic white IVDUs. Blacks [odds ratio (OR) = 9.0, 95% confidence interval (CI) = 5.1-15.9] and Hispanics (OR = 4.1, 95% CI = 1.9-8.8) were at increased risk of HIV-1 infection, relative to non-Hispanic whites. Those who lived closer to New York City, injected drugs more frequently, used intravenous drugs for a longer duration, used shooting galleries, had greater numbers of sexual partners, had human cytomegalovirus (CMV) or hepatitis B virus (HBV) antibodies, and had the lowest annual incomes were also at increased risk. However, none of these other factors accounted for the black and Hispanic HIV-1 risk in stratified analysis. Black race, Hispanic ethnicity, proximity to New York City, and number of drug injections in the past year each also remained significant, independent risk factors in a multivariate analysis. The increased HIV-1 risk of nonwhite IVDUs remained unexplained. Behavioral, sociologic, and/or biologic factors not identified in this study may modulate HIV-1 transmission dynamics in IVDUs. .A D'Aquila RT; Peterson LR; Williams AB; Williams AE. .I 201908 .U 90011757 .S J Acquir Immune Defic Syndr 9001; 2(5):514-7 .M Acquired Immunodeficiency Syndrome/*ET/MI; Human; HIV/*. .T Does HIV cause AIDS? [letter; comment] .P COMMENT; LETTER. .A Duesberg P. .I 201909 .U 90011777 .S J Pharmacol Exp Ther 9001; 251(1):105-12 .M Animal; Apomorphine/PD; Avoidance Learning/DE; Behavior, Animal/*DE; Cebus; Dextroamphetamine/PD; Dopamine/AI; Imidazoles/*PD; Male; Mice; Motor Activity/DE; Pyrimidines/*PD; Rats; Rats, Inbred Strains; Saimiri; Stereotyped Behavior/DE; Tranquilizing Agents, Major/*/PD. .T CI-943, a potential antipsychotic agent. I. Preclinical behavioral effects. .P JOURNAL ARTICLE. .W CI-943 (8-ethyl-7,8-dihydro-1,3,5-trimethyl-1H-imidazo[1,2-c] pyrazolo[3,4-e]-pyrimidine) is a novel agent that is chemically unrelated to available antipsychotics and is not a dopamine receptor antagonist. Like available antipsychotics, CI-943 reduces spontaneous locomotion in mice and rats and inhibits compulsive cage climbing induced by apomorphine in mice at doses that do not produce ataxia. However, CI-943 enhances rather than inhibits the locomotor stimulant effects of d-amphetamine in mice and rats. Unlike dopamine antagonists, CI-943 does not affect stereotypy caused by apomorphine or amphetamine in rats. CI-943 displays an antipsychotic-like profile in conditioned avoidance tests, inhibiting one-way avoidance in rats at doses that do not impair escape and inhibiting continuous avoidance in rats and squirrel monkeys at doses that do not impair shock termination responding. Although high doses of CI-943 produce dystonic movements in haloperidol-sensitized monkeys, CI-943 differs from dopamine antagonists that produce extrapyramidal dysfunction in humans in that doses of CI-943 that are sufficient to inhibit avoidance responding in monkeys do not produce extrapyramidal dysfunction. Unlike dopamine antagonists that produce tardive dyskinesia, CI-943 administered repeatedly at high doses does not produce behavioral supersensitivity to dopamine agonists in rats. These results demonstrate that CI-943 resembles available antipsychotics in some preclinical behavioral tests commonly used to predict antipsychotic efficacy but differs from dopamine antagonists in tests predictive of dopamine receptor antagonism and antipsychotic-induced neurological dysfunction. .A Heffner TG; Downs DA; Meltzer LT; Wiley JN; Williams AE. .I 201910 .U 90011778 .S J Pharmacol Exp Ther 9001; 251(1):113-22 .M Animal; Apomorphine/PD; Brain Chemistry/*DE; Clozapine/PD; Dopamine/ME; Haloperidol/ME/PD; Imidazoles/*PD; In Vitro; Male; Mice; Neuroregulators/*ME; Norepinephrine/ME; Prolactin/BL; Pyrimidines/*PD; Rats; Rats, Inbred Strains; Serotonin/ME; Spiperone/ME; Tranquilizing Agents, Major/*PD. .T CI-943, a potential antipsychotic agent. II. Neurochemical effects. .P JOURNAL ARTICLE. .W The effects of CI-943 (a novel 8-ethyl-7,8-dihydro-1,3,5-trimethyl-1H-imidazo[1,2-c]pyrazolo[3,4- e]pyrimidine compound exhibiting a favorable antipsychotic profile in animal tests) on neurochemical parameters related to biogenic amine neurons have been studied in rat brain. CI-943 (1-40 mg/kg p.o. and 20 mg/kg i.p.) accelerated the turnover of dopamine (DA) in rat brain as demonstrated by the enhancement of levels of the DA metabolites homovanillic acid, 3,4-dihydroxyphenylacetic acid or 3-methoxytyramine and by the enhancement rate of DA synthesis in either striatum or mesolimbic regions. These increases in DA turnover induced by CI-943 are not due to DA receptor blockade as CI-943, unlike known antipsychotics, did not exhibit affinity for DA receptors either in vitro or in vivo and did not affect rat serum basal prolactin levels. Amfonelic acid enhanced the action of haloperidol in increasing striatal homovanillic acid with no effect on that of CI-943 and clozapine, suggesting that CI-943, like clozapine, would be predicted to have a low risk of extrapyramidal side effects as compared to haloperidol. Chronic administration of CI-943 (40 mg/kg i.p.) to rats for 28 days did not affect the affinity or number of striatal DA receptors; in comparison haloperidol (0.5 mg/kg i.p.) caused an increase in number of DA receptors with no change in affinity. Measures of serotonergic function were increased; noradrenergic function was not affected by CI-943, nor did it exhibit affinity for a number of central nervous system receptors in vitro. The molecular mechanism by which CI-943 increases brain DA turnover is not known at this time but appears to be unique in comparison to known antipsychotic agents. .A Pugsley TA; Coughenour LL; Myers SL; Shih YH; Courtland GG; Berghoff W; Stewart SF. .I 201911 .U 90011779 .S J Pharmacol Exp Ther 9001; 251(1):123-30 .M Action Potentials/DE; Animal; Brain/DE; Comparative Study; Dopamine/AI/*PH; Dopaminergic Agents/PD; Imidazoles/*PD; Male; Neurons/*DE; Pyrimidines/*PD; Rats; Rats, Inbred Strains; Tranquilizing Agents, Major/*PD. .T CI-943, a potential antipsychotic agent. III. Evaluation of effects on dopamine neuronal activity. .P JOURNAL ARTICLE. .W CI-943 (8-ethyl-7,8-dihydro-1,3,5-trimethyl-1H-imidazo[1,2- c]pyrazolo[3,4-e]pyrimidine) has been identified as a novel potential antipsychotic agent that does not bind to dopamine (DA) receptors. In the present studies, the effects of acute and chronic administration of CI-943 on the electrophysiological activity of A9 and A10 DA neurons were assessed and compared to the effects of DA antagonist antipsychotic drugs. Acute administration of CI-943 did not increase the base-line firing rate (10-20 mg/kg i.p.), did not increase the number of spontaneously active DA neurons (40 mg/kg p.o.) and did not antagonize the effects of apomorphine or amphetamine on A9 or A10 DA neurons (20-40 mg/kg i.p.). A high dose of CI-943 (40 mg/kg i.p.) decreased the firing rate of A9 and A10 DA neurons, an effect that was not antagonized by haloperidol. In contrast, haloperidol increased the base-line firing rate (0.5 mg/kg i.p.), increased the number of spontaneously active DA neurons (0.5 mg/kg p.o.) and antagonized the effects of apomorphine and d-amphetamine on A9 and A10 DA neurons (0.1 mg/kg i.p.). Repeated (21 days) administration of CI-943 (36 mg/kg/day p.o.) did not alter the number of spontaneously active A9 DA neurons but increased the number of active A10 DA neurons. In contrast, repeated administration of haloperidol (0.4 mg/kg/day p.o.) decreased the number of spontaneously active DA neurons in A9 and A10, whereas repeated administration of clozapine (19 mg/kg/day p.o.) decreased the number of active A10 DA neurons but increased the number of active A9 DA neurons.(ABSTRACT TRUNCATED AT 250 WORDS) .A Meltzer LT; Christoffersen CL; Heffner TG; Freeman AS; Chiodo LA. .I 201912 .U 90011780 .S J Pharmacol Exp Ther 9001; 251(1):131-41 .M Animal; Binding Sites; Binding, Competitive; Caudate Nucleus/*ME; Cocaine/*ME; Female; In Vitro; Macaca fascicularis; Male; Putamen/*ME; Saimiri; Support, U.S. Gov't, P.H.S.; Transmitter Uptake Inhibitors, Neuronal/PD. .T Effects of cocaine and related drugs in nonhuman primates. I. [3H]cocaine binding sites in caudate-putamen. .P JOURNAL ARTICLE. .W Specific binding sites for [3H]cocaine were identified in caudate-putamen membranes prepared from nonhuman primate brains (Macaca fascicularis and Saimiri sciureus). Saturation of the sites was determined in competition studies using a fixed concentration of [3H]cocaine (2.7 nM) and increasing concentrations of unlabeled cocaine (1 pM-100 microM). Computer resolution of the shallow displacement curve (nH, 0.58) revealed that a two-component binding model [Kd1, 19.2 nM, maximum binding1 (Bmax1), 28.3 pmol/g of tissue; Kd2, 1120 nM, Bmax2, 431 pmol/g of tissue] was statistically preferred over a one-component model (K.50, 283 nM, Bmax, 471 pmol/g of tissue). Binding of [3H]cocaine was NaCl-dependent, with specific binding reduced by 72% when NaCl (100 mM) was omitted from the incubation medium. [3H]Cocaine was displaced stereoselectively by the enantiomers of cocaine and by the diastereoisomers of cocaine and its phenyltropane analog. Cocaine congeners displaced specifically bound [3H]cocaine with IC50 values ranging from 17 nM to over 100 microM in the following rank order of potency: WIN 35,428 greater than WIN 35,065-2 greater than (-)-cocaine greater than WIN 35,981 greater than (-)-norcocaine greater than WIN 35,140 greater than (+)-cocaine, (+)-pseudococaine greater than 3 alpha-tropanyl-1H-indole-carboxylic acid ester greater than 1 alpha H-3 alpha-5 alpha H-tropan-3-yl-3,5-dichlorobenzoate greater than benzoylecgonine, benzoylnorecgonine and (-)-pseudococaine. Several monoamine uptake inhibitors structurally unrelated to cocaine also displaced [3H]cocaine with IC50 values ranging from 1.6 nM to 50 microM. The rank order of potency was: ( +/- )-trans-3-(3',4'-dichlorophenyl)-N-methyl-1-indanamine greater than mazindol greater than nomifensine greater than methylphenidate 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]- 4-(3-phenylpropyl)piperazine, N-[1-(2- benzo(b)thiophenyl)cyclohexyl]piperidine greater than (-)-cocaine greater than 1-amino-4-phenylbicyclo-[2,2,2]-octane greater than bupropion, nisoxetine greater than desipramine, talsupram greater than citalopram. Other drugs, including the dopamine releasing agent (+)-amphetamine and the dopamine receptor agonists (-)-apomorphine, (+)-4-propyl-9-hydroxy-naphthoxazine, quinpirole and SKF 38393 were weak displacers of [3H]cocaine. Monoamine neurotransmitters also were relatively weak, but dopamine was considerably more potent than either norepinephrine or serotonin.(ABSTRACT TRUNCATED AT 400 WORDS) .A Madras BK; Fahey MA; Bergman J; Canfield DR; Spealman RD. .I 201913 .U 90011781 .S J Pharmacol Exp Ther 9001; 251(1):142-9 .M Animal; Behavior, Animal/*DE; Binding Sites; Binding, Competitive; Biogenic Monoamines/ME; Cocaine/AA/ME/*PD; Comparative Study; Conditioning, Operant/DE; Male; Saimiri; Support, U.S. Gov't, P.H.S.. .T Effects of cocaine and related drugs in nonhuman primates. II. Stimulant effects on schedule-controlled behavior. .P JOURNAL ARTICLE. .W The behavioral effects of cocaine were compared with those of several cocaine derivatives and structurally distinct drugs that inhibit monoamine uptake. Squirrel monkeys were trained to respond under a fixed-interval schedule of stimulus-shock termination, and dose-effect curves were determined by administering cumulative doses i.v. Among the cocaine congeners, (-)-cocaine, (+)-pseudococaine and 1 alpha H, 3 alpha, 5 alpha H-tropan-3-yl-3,5-dichlorobenzoate produced dose-related increases in response rate, whereas (-)-pseudococaine, (-)-benzoylecgonine and (-)-benzoylnorecgonine did not increase responding consistently over a 100-fold or greater range of doses. 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine, which selectively inhibits uptake of dopamine, and mazindol, methylphenidate, nomifensine and bupropion, which inhibit uptake of dopamine as well as other monoamines, had behavioral effects similar to those of cocaine. In contrast, desipramine and citalopram, which selectively inhibit uptake of norepinephrine and serotonin, respectively, produced only dose-related decreases in response rate. The results combined with previous studies demonstrate a close correspondence between the potencies of 15 different drugs for producing cocaine-like behavioral effects and for displacing specifically bound [3H]cocaine in caudate-putamen. These findings are consistent with the view that the behavioral effects of cocaine and related drugs are linked to their actions at specific cocaine recognition sites associated with the dopamine uptake system. .A Spealman RD; Madras BK; Bergman J. .I 201914 .U 90011784 .S J Pharmacol Exp Ther 9001; 251(1):16-20 .M Animal; Arteries/*DE; Cats; Comparative Study; In Vitro; Male; Norepinephrine/AI/*PD; Prazosin/PD; Rats; Rats, Inbred WKY; Receptors, Adrenergic, Alpha/*PH; Species Specificity; Support, U.S. Gov't, P.H.S.; Vasoconstriction/DE; Yohimbine/PD. .T Variation in sensitivity of six cat and six rat arteries to norepinephrine can be related to differences in agonist affinity and receptor reserve. .P JOURNAL ARTICLE. .W The sensitivity of contraction to norepinephrine and alpha-1-adrenoceptor affinity and reserve were measured in six rat and six cat arteries. These were the thoracic and abdominal aorta, superior mesenteric, renal, and femoral arteries of both species, and rat tail and cat splenic arteries. Sensitivity to norepinephrine differed by more than a factor of 30 in the rat and 20 in the cat. Rank order of sensitivities were in general similar in the two species. In rat and cat there was a significant correlation between sensitivity to norepinephrine and alpha-1 adrenoceptor affinity and also between sensitivity and receptor reserve, expressed as -antilog (pD2 - pKA). In the rat the contribution of affinity to these differences in sensitivity was greater than that of receptor reserve. In the cat arteries, receptor reserve is the more important factor. These results support the "variable receptor affinity hypothesis." This proposes that the affinity of a receptor can vary, and this may be due to differences in receptor structure, local membrane microenvironment, and extent of influence of intracellular mechanisms. The hypothesis proposes that variation in affinity can have a significant impact on tissue sensitivity. .A Oriowo MA; Bevan JA; Bevan RD. .I 201915 .U 90011786 .S J Pharmacol Exp Ther 9001; 251(1):169-74 .M Animal; Ganglionic Stimulants/*AI; Guanidines/*PD; Guinea Pigs; In Vitro; Male; Membrane Potentials/DE; Myenteric Plexus/DE; Neurons/*DE; Phenazocine/AA/PD; Receptors, Endorphin/*PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T 1,3-Di(2-tolyl)guanidine blocks nicotinic response in guinea pig myenteric neurons. .P JOURNAL ARTICLE. .W Ditolylguanidine (DTG) is a ligand which binds with high affinity to neuronal sigma receptors. Activation of sigma receptors inhibits the release of acetylcholine (ACh) from guinea pig ileum myenteric plexus preparations. A study was therefore undertaken to investigate the action of sigma receptor ligands on single neurons. Nicotinic responses to locally applied ACh onto single neurons of the guinea pig ileum myenteric plexus were studied using intracellular recording techniques. DTG and (+)-SKF10047 (N-allylnormetazocine) produced a concentration-dependent suppression of the depolarization of enteric neurons evoked by ionophoresis of ACh. The EC50 values for DTG and (+)-SKF10047 were 4.7 and 3.8 microM, respectively, and were similar to that for hexamethonium (3.2 microM). The inhibition of the ACh-depolarization was not mediated at sigma receptors because (-)SKF10047 and Bridge-DPG (2-imino-1,3H-dibenzo[d,f]-[1,3]-diazepine), which are inactive at sigma receptors, were as potent as DTG and (+)-SKF10047. DTG and hexamethonium (each at 1 microM) were more effective blockers of ACh-induced inward currents at a holding potential of -100 mV than at -40 mV. This voltage dependence is consistent with a channel blocking mechanism. DTG (10 microM) did not affect the depolarization (mediated by 5-HT3 receptors) induced by pressure application of 5-HT onto single neurons. DTG and Bridge-DPG inhibited contractures of the longitudinal muscle-myenteric plexus preparation elicited by dimethylphenylpiperazinium noncompetitively (EC50 values were 8.0 and 12.3 microM, respectively) whereas DTG but not Bridge-DPG inhibited 5-HT-induced contractions of the longitudinal muscle-myenteric plexus noncompetitively.(ABSTRACT TRUNCATED AT 250 WORDS) .A Galligan JJ; Campbell BG; Kavanaugh MP; Weber E; North RA. .I 201916 .U 90011787 .S J Pharmacol Exp Ther 9001; 251(1):175-82 .M Animal; Comparative Study; Ganglionic Blockaders/PD; Ganglionic Stimulants/PD; Human; Medulloblastoma/*ME; Pheochromocytoma/*ME; Rats; Receptors, Nicotinic/*DE/ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured. .T Pharmacological distinctions between functional nicotinic acetylcholine receptors on the PC12 rat pheochromocytoma and the TE671 human medulloblastoma. .P JOURNAL ARTICLE. .W Some properties of functional nicotinic acetylcholine receptors (nAcChoR) expressed by the PC12 rat pheochromocytoma or the TE671 human medulloblastoma were studied by the use of an isotopic rubidium ion efflux assay. The assay involves active uptake of 86Rb+ via a ouabain-sensitive mechanism to load cells with isotopic tracer and the subsequent release of ion from cells through agonist-activated opening of nAcChoR-coupled ion channels. For either cell line the rate of receptor-mediated ion efflux is time-dependent and falls as duration of exposure to agonist increases. However, dose-response curves for agonist activation of receptor function (or for antagonist blockade of agonist activation) are temporally invariant. Dose-response curves have characteristic shapes for a given agonist, and the relative and absolute potencies of agonists differ between TE671 and PC12 cells. Most notably, nicotine and cytisine are more potent activators of receptor function on the PC12 cell line whereas TE671 cell nAcChoR are more sensitive to activation by isoarecolone and suberyldicholine. PC12 cell nAcChoR are more sensitive to blockade by the classic "ganglionic" blockers, mecamylamine and hexamethonium, and by the molluscan substance, neosurugatoxin, than are nAcChoR on TE671 cells. The results, illustrating differences in the pharmacological profiles of drugs acting as functional nAcChoR on TE671 and PC12 cells, suggest that structural differences exist in nAcChoR active site(s) and are consistent with the notion that functional nAcChoR are a heterogeneous family of macromolecules. .A Lukas RJ. .I 201917 .U 90011789 .S J Pharmacol Exp Ther 9001; 251(1):188-92 .M Amides/PD; Animal; Biological Transport/DE; Comparative Study; Kidney Cortex/*DE/ME; Male; Nicotinamide/PD; NAD/ME; Phosphates/*ME; Picolinic Acids/*PD; Rats; Rats, Inbred Strains; Sodium/*ME; Support, U.S. Gov't, P.H.S.. .T Specific inhibition of rat renal Na+/phosphate cotransport by picolinamide. .P JOURNAL ARTICLE. .W Nicotinamide is both a precursor for NAD synthesis and an inhibitor of intracellular NAD hydrolysing enzymes. Overnight treatment of rats with nicotinamide causes dose-dependent inhibition of the Na+/phosphate cotransporter in the renal brush border membrane. Picolinamide is an isomer of nicotinamide that cannot be used for NAD synthesis. Picolinamide was used in the present study to explore the possibility that inhibition of Na+/phosphate cotransport may be related to inhibition of NAD hydrolyzing enzymes. Overnight treatment of rats with picolinamide, administered as a single injection (4 mmol/kg), inhibited Na+/phosphate cotransport by isolated renal brush border membrane vesicles. Like nicotinamide, the inhibition by picolinamide occurred in thyroparathyroidectomized rats, was specific for Na+/phosphate cotransport and was accompanied by a decrease in the apparent Vmax. In contrast to nicotinamide, there was only a small increase (1.5-fold) in renal cortical NAD content after picolinamide treatment. Direct incubation of isolated proximal tubules with thymidine, a potent inhibitor of NAD hydrolysis by intracellular enzymes, produced no change in Na+/phosphate cotransport. Thus, specific inhibition of renal Na+/phosphate cotrasport by picolinamide in vivo is unlikely due to inhibition of NAD hydrolyzing enzymes. It is suggested, based on data from in vitro studies, that a cyclic AMP-dependent mechanism may be involved. .A Campbell PI; al-Mahrouq HA; Abraham MI; Kempson SA. .I 201918 .U 90011790 .S J Pharmacol Exp Ther 9001; 251(1):193-8 .M Alcohol Dehydrogenase/*ME; Aldehyde Dehydrogenase/*ME; Animal; Glutathione/ME; In Vitro; Kinetics; Liver/*EN; Male; Oxidation-Reduction; Rats; Rats, Inbred Strains; Subcellular Fractions/EN; Support, U.S. Gov't, P.H.S.. .T Metabolism of the glutathione-acrolein adduct, S-(2-aldehydo-ethyl)glutathione, by rat liver alcohol and aldehyde dehydrogenase. .P JOURNAL ARTICLE. .W The oxidative and reductive metabolism of the acrolein-glutathione adduct, S-(2,aldehydo-ethyl)glutathione, by rat liver aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH) was characterized. The glutathione-acrolein adduct is oxidized to the respective acid by two different forms of ALDH contained in rat liver cytosol which are distinct from two forms of ALDH present in the mitochondria also capable of oxidizing the aldehyde moiety of the adduct. Extensive kinetic characterization (Km, Vmax and V/K parameters) of the ALDH enzymes suggest that the glutathione-acrolein adduct is oxidized most efficiently by one form of mitochondrial ALDH which is 3.5 to 175 times more active (based on V/K comparisons) than the other forms of mitochondrial and cytosolic ALDH evaluated. The glutathione-acrolein adduct is also subject to reductive metabolism by rat liver ALH. However, the Km value (877 microM) for reduction of the adduct suggests that this would be a minor pathway of metabolism. Collectively, these results indicate that the glutathione-acrolein adduct formed after exposure to acrolein, or as a result of allyl alcohol oxidation and cyclophosphamide metabolism, can be oxidized by hepatic ALDH or ADH, respectively. However, the kinetic parameters for these pathways suggest that micromolar concentrations of this adduct may accumulate before these enzyme systems mediate significant oxidative or reductive pathways of detoxification. The proposition that the glutathione-acrolein adduct may play a role in acrolein-mediated hepatotoxicity is discussed. .A Mitchell DY; Petersen DR. .I 201919 .U 90011791 .S J Pharmacol Exp Ther 9001; 251(1):199-206 .M Airway Resistance/*DE; Animal; Bronchi/DE; Female; Guinea Pigs; Male; Phosphodiesterase Inhibitors/PD; Pyridazines/PD; Pyrrolidinones/PD; Trachea/DE; 3',5'-Cyclic AMP Phosphodiesterase/*AI. .T Role of low Km cyclic AMP phosphodiesterase inhibition in tracheal relaxation and bronchodilation in the guinea pig. .P JOURNAL ARTICLE. .W This study evaluated the relationship between inhibition of the rolipram-sensitive and the CI-930-sensitive low Km cyclic AMP-specific phosphodiesterase (PDE) isozymes (PDE IIIRO and PDE IIIc, respectively) and bronchomotor tone in the guinea pig. Rolipram and CI-930 exhibited biphasic concentration-response relationships for relaxation of carbachol-, histamine- and leukotriene D4-contracted trachea. However, each agent produced a monophasic (sigmoidal) concentration-response curve when tested in the presence of a fixed concentration (3 microM) of the other. The same relationships were observed for inhibition of tracheal peak III PDE isolated via diethylaminoethyl-cellulose chromatography. Whereas CI-930 was approximately equipotent inhibiting PDE IIIc and relaxing rolipram-pretreated trachea, rolipram was substantially more potent (EC50 = 0.02 microM) in relaxing CI-930-pretreated trachea than in inhibiting CI-930-pretreated PDE III (PDE IIIRO, IC50 = 2.6 microM). Among a series of PDE inhibitors, there was a highly significant correlation (r = 0.89, P less than .01) between PDE IIIc inhibition (i.e., PDE III in the presence of rolipram) and rolipram-pretreated tracheal relaxation, but not between PDE IIIRO inhibition and CI-930-pretreated tracheal relaxation (r = 0.23). Nine of the PDE inhibitors used in this study have been reported to displace rolipram from a high-affinity binding site in rat brain. A highly significant correlation between relaxation of CI-930-pretreated trachea and displacement of rolipram binding by these agents was observed (r = 0.97, P less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS) .A Harris AL; Connell MJ; Ferguson EW; Wallace AM; Gordon RJ; Pagani ED; Silver PJ. .I 201920 .U 90011792 .S J Pharmacol Exp Ther 9001; 251(1):207-15 .M Animal; Anticonvulsants/*PD; Antidepressive Agents/PD; Antitussive Agents/*PD; Binding Sites/DE; Brain/*DE/ME; Dextromethorphan/*ME; Guinea Pigs; In Vitro; Ion Channels/DE; Levorphanol/*AA; Male; Receptors, Endorphin/ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tranquilizing Agents, Major/PD. .T High affinity dextromethorphan binding sites in guinea pig brain. Effect of sigma ligands and other agents. .P JOURNAL ARTICLE. .W Dextromethorphan (DM), a non-narcotic antitussive, binds in the guinea pig brain to specific high- and low-affinity sites with Kd values of 57 nM and 24 microM, respectively (Musacchio et al., 1988). The antitussives carbetapentane, caramiphen, butamirate and dimethoxanate competed with the high-affinity binding of [3H]DM at pH 7.4 with nanomolar Ki values. Sigma site ligands showed high affinity for [3H]DM binding sites. The rank order of potency was: haloperidol greater than (+)-pentazocine greater than (+)-cyclazocine greater than 3-(-3-hydroxyphenyl)-N-(1-propyl)piperidine greater than (+)-N-allylnormetazocine greater than (-)-butaclamol much greater than (+)-butaclamol (-)-N-allylnormetazocine. The antipsychotic perphenazine competed with low nanomolar Ki values, whereas rimcazole was weaker. The antidepressant opipramol and the benzomorphan (+)2'methoxyphenazocine were the most effective drugs tested, with Ki values of 0.4 nM. By contrast, MK-801 and phencyclidine hydrochloride were very weak competitors for [3H]DM binding. The diphenylalkylamines were the most effective competitors of the calcium channel blocking agents: prenylamine and cinnarizine had Ki values of 17 and 22 nM, respectively. Lidoflazine and hydroxyzine were slightly less potent, but nifedipine and the benzothiazepine diltiazem were much weaker. Potassium channel blockers inhibited DM binding in pharmacologically relevant concentrations: primaquine was the most effective with a Ki of 0.5 microM. Other antimalarial potassium channel blockers tested inhibited binding in the micromolar range. 4-Aminopyridine and tetraethylammonium had Ki values of 0.76 and 1.40 mM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) .A Klein M; Musacchio JM. .I 201921 .U 90011793 .S J Pharmacol Exp Ther 9001; 251(1):21-6 .M Analgesics/AD/*PD; Animal; Body Temperature/DE; Brain/*DE; Drug Tolerance; Male; Pyrrolidines/AD/*PD; Rats; Rats, Inbred Strains; Receptors, Endorphin/*DE; Spinal Cord/*DE; Support, U.S. Gov't, P.H.S.; Time Factors. .T Effect of chronic administration of U-50,488H on tolerance to its pharmacological actions and on multiple opioid receptors in rat brain regions and spinal cord. .P JOURNAL ARTICLE. .W The effects of chronic administration of U-50,488H (trans-3,4-dichloro-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeacetamide ), a selective kappa opioid agonist, on the development of tolerance to its analgesic and hypothermic effects and on mu, delta and kappa opioid receptors in brain regions and spinal cord of male Sprague-Dawley rats were determined. Rats were injected i.p. twice daily with 25 mg/kg of U-50,488H for 4 days. The development of tolerance to the analgesic and hypothermic effects of U-50,488H was almost complete after 4 days of treatment. [3H]Tyr-D-Ala-Gly-MePhe-Gly-ol (DAMGO), [3H]Tyr-D-Ser-Gly-Phe-Leu-Thr (DSTLE) and [3H]ethylketocyclazocine (EK) were used as ligands for mu, delta and kappa opioid receptors, respectively. The binding of [3H]DAMGO to membranes prepared from various brain regions (pons + medulla, midbrain, hypothalamus, corpus striatum and cortex) and spinal cord was unaffected by chronic administration of U-50,488H. The binding of [3H]DSTLE in U-50,488H-treated rats was decreased in spinal cord and increased in corpus striatum. The binding of [3H]EK to membranes prepared from pons + medulla, midbrain, cortex and spinal cord was decreased whereas it was increased in the corpus striatum. The changes in the binding of [3H]DSTLE and [3H]EK after chronic treatment with U-50,488H were due to changes in the maximum binding values and not in the Kd values. The results indicate that, in the rat, chronic administration of U-50,488H results in the development of tolerance to its analgesic and hypothermic effects and down-regulation of kappa and delta opioid receptors in the spinal cord and an up-regulation in the corpus striatum.(ABSTRACT TRUNCATED AT 250 WORDS) .A Bhargava HN; Gulati A; Ramarao P. .I 201922 .U 90011794 .S J Pharmacol Exp Ther 9001; 251(1):216-23 .M Analgesics/AD/*PD; Animal; Dose-Response Relationship, Drug; Drug Tolerance/*; Infusions, Parenteral; Male; Rats; Rats, Inbred Strains; Spinal Cord/*DE; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Time Factors. .T Time course characteristics of tolerance development to continuously infused antinociceptive agents in rat spinal cord. .P JOURNAL ARTICLE. .W By using a constant-rate, fixed concentration intrathecal infusion model, the time course of change in hot plate (HP) response latencies over a 7-day period was examined in rats receiving constant infusion of saline (vehicle), morphine (MOR (2, 6 or 20 nmol/hr), sufentanil (SUF) (0.06, 0.2 or 0.6 nmol/hr), D-Ala2-MePhe4-Gly-ol5-enkephalin (DAMGO) (0.1, 0.3 or 1.0 nmol/hr) (mu opioids), D-Ala2-D-Leu5-enkephalin (DADLE) (2,6 or 20 nmol/hr) (delta opioid), ST-91 (3, 10 or 30 nmol/hr) (alpha-2 agonist) or the combination of ST-91 + MOR. Three important observations were made: 1) A concentration-dependent elevation in HP latency was observed on day 1 (order of potency: DAMGO = SUF greater than MOR greater than or equal to DADLE greater than or equal to ST-91 + MOR greater than or equal to ST-91) with a gradual return to saline-infused values observed for all concentrations of all drugs by 3 to 5 days. 2) The rate of tolerance development, estimated by calculation of the exponential decay half-life from peak day 1 HP, was not different as a function of drug dose. The area under the 7-day tolerance curve (response latency x day) was directly proportional to infusion concentration and to peak HP effect on day 1. These two calculations both suggest that the rate at which the tolerance adaptation of drug occurs to agonist effects is similar for agents acting upon mu, delta and alpha-2 receptors in rat spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS) .A Stevens CW; Yaksh TL. .I 201923 .U 90011796 .S J Pharmacol Exp Ther 9001; 251(1):230-7 .M Animal; Cyclazocine/*AA/PD; Diuresis/DE; Hemodynamics/DE; Hypertension/*PP; Kidney/*DE/IR; Male; Pyrrolidines/*PD; Rats; Rats, Inbred SHR; Receptors, Endorphin; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Sympathetic Nervous System/DE. .T Role of renal nerves in excretory responses to administration of kappa agonists in conscious spontaneously hypertensive rats. .P JOURNAL ARTICLE. .W The present study examined whether the renal sympathetic nerves contribute to the renal excretory responses produced by kappa opioid receptor agonist administration in conscious spontaneously hypertensive rats (SHR). Intravenous infusion of the kappa opioid receptor agonists, ketocyclazocine (KC) and U-50488H, produced increases in urine flow rate. KC and U-50488H infusion also resulted in a marked and sustained antinatriuresis which was promptly reversed by low-dose naloxone (50 micrograms/kg i.v.), thus suggesting an opioid receptor-mediated action of both agonists. Although these kappa agonists did not produce changes in glomerular filtration rate or renal plasma flow, efferent renal sympathetic nerve activity increased with the same time course as the antinatriuretic response. To investigate whether the decrease in urinary sodium excretion was mediated via the increase in efferent renal sympathetic nerve activity, experiments were repeated in SHR with prior bilateral renal denervation. These studies demonstrated that similar renal excretory responses (diuresis and a naloxone reversible antiinatriuresis occurred during infusion of KC and U-50488H in renal denervated as were seen in intact SHR. These studies indicate that the renal excretory responses to the kappa opioid agonists KC and U-50488H are not mediated through changes in renal hemodynamics or via a pathway requiring intact renal innervation. Because an antinatriuretic response was observed in renal denervated SHR, this suggests that kappa opioid receptor agonists may influence the renal tubular reabsorption of sodium by additional naloxone-sensitive mechanisms independent of intact renal innervation. .A Kapusta DR; Jones SY; DiBona GF. .I 201924 .U 90011797 .S J Pharmacol Exp Ther 9001; 251(1):238-46 .M Animal; Cerebral Cortex/ME; Corpus Striatum/ME; Discriminant Analysis; In Vitro; Male; Rats; Rats, Inbred Strains; Receptors, Dopamine/*ME; Receptors, Serotonin/*ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tranquilizing Agents, Major/*CL/ME. .T Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin2 pKi values. .P JOURNAL ARTICLE. .W The pKi values of 13 reference typical and 7 reference atypical antipsychotic drugs (APDs) for rat striatal dopamine D-1 and D-2 receptor binding sites and cortical serotonin (5-HT2) receptor binding sites were determined. The atypical antipsychotics had significantly lower pKi values for the D-2 but not 5-HT2 binding sites. There was a trend for a lower pKi value for the D-1 binding site for the atypical APD. The 5-HT2 and D-1 pKi values were correlated for the typical APD whereas the 5-HT2 and D-2 pKi values were correlated for the atypical APD. A stepwise discriminant function analysis to determine the independent contribution of each pKi value for a given binding site to the classification as a typical or atypical APD entered the D-2 pKi value first, followed by the 5-HT2 pKi value. The D-1 pKi value was not entered. A discriminant function analysis correctly classified 19 of 20 of these compounds plus 14 of 17 additional test compounds as typical or atypical APD for an overall correct classification rate of 89.2%. The major contributors to the discriminant function were the D-2 and 5-HT2 pKi values. A cluster analysis based only on the 5-HT2/D2 ratio grouped 15 of 17 atypical + one typical APD in one cluster and 19 of 20 typical + two atypical APDs in a second cluster, for an overall correct classification rate of 91.9%. When the stepwise discriminant function was repeated for all 37 compounds, only the D-2 and 5-HT2 pKi values were entered into the discriminant function.(ABSTRACT TRUNCATED AT 250 WORDS) .A Meltzer HY; Matsubara S; Lee JC. .I 201925 .U 90011798 .S J Pharmacol Exp Ther 9001; 251(1):247-52 .M Analgesics; Animal; Antidiarrheals/*; Benzimidazoles/*PD; Calmodulin/*AI; Chlorpromazine/PD; Comparative Study; Gastrointestinal Transit/*DE; Loperamide/PD; Male; Mice; Mice, Inbred ICR; Morphine/PD; Rats; Rats, Inbred Strains; Support, U.S. Gov't, P.H.S.. .T Novel calmodulin antagonist CGS 9343B inhibits secretory diarrhea. .P JOURNAL ARTICLE. .W The goal of this study was to determine whether secretory diarrhea could be ameliorated by pharmacological alteration of the second messenger systems which mediate intestinal fluid and electrolyte transport. Calmodulin is an important intermediate in the mucosal signal-transduction pathways that regulate intestinal NaCl transport. We tested a selective inhibitor of calmodulin, CGS 9343B, for antidiarrheal activity in two different models of secretory diarrhea. Diarrhea was induced in mice by p.o. administration of castor oil (0.6 ml) and in rats by i.p. injection of PGE2 (150 micrograms). We compared the antidiarrheal effects of CGS 9343B to other prototype antidiarrheal agents including morphine, loperamide and chlorpromazine in the castor oil-induced model of secretory diarrhea in mice. CGS 9343B was the most potent of these agents, eliminating diarrhea in 100% of mice at a dose of 1 mg/kg (p.o.). Morphine, loperamide and chlorpromazine were 3 to 10 times weaker than CGS 9343B. In this model, we measured changes in the amount of feces eliminated (grams) and loss of body weight (grams) as indicators of the rate of intestinal propulsion, based on the assumption that reduced fecal passage and concomitantly smaller weight loss represented reduced propulsion of intestinal contents, or constipation. Although the other agents caused equal degrees of constipation and antidiarrheal activity, CGS 9343B did not exert any significant antipropulsive effects at antidiarrheal doses in castor oil-treated mice. To further differentiate these agents on the basis of antipropulsive activity, we compared them for effects on the rate of transit of a p.o. administered radioactive marker in normal mice (noncastor oil-treated).(ABSTRACT TRUNCATED AT 250 WORDS) .A Shook JE; Burks TF; Wasley JW; Norman JA. .I 201926 .U 90011799 .S J Pharmacol Exp Ther 9001; 251(1):253-7 .M Adrenergic Alpha Receptor Agonists/*PD; Adrenergic Alpha Receptor Blockaders/*PD; Animal; Autonomic Fibers, Preganglionic/DE; Dogs; Dopamine/PD; Dopaminergic Agents/*PD; Ganglia, Sympathetic/*DE; Heart Rate/DE; Male; Norepinephrine/PD; Receptors, Dopamine/*AI; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Effects of alpha adrenoceptor and dopamine receptor agonists and antagonists on ganglionic transmission. .P JOURNAL ARTICLE. .W Effects of alpha adrenoceptor and dopamine (DA) receptor agonists and antagonists on ganglionic transmission were studied in pentobarbital-anesthetized, open-chest dogs. Changes in tachycardia produced by preganglionic cardiac nerve stimulation were monitored as a measure of ganglionic transmission. Several agonists, injected i.a. into the blood supply of the stellate ganglion, inhibited ganglion transmission. This effect was localized to the ganglion as none of the agonists, in the highest doses studied, inhibited tachycardia produced by postganglionic cardiac nerve stimulation. The potency order of the agonists was UK 14,304 (alpha-2 adrenoceptor agonist) greater than norepinephrine (NE) greater than dipropyl DA (DA2 dopamine receptor agonist) greater than DA greater than or equal to phenylephrine (alpha-1 adrenoceptor agonist) greater than fenoldopam (DA1 dopamine receptor agonist). UK 14,304 was over 200 times more potent than fenoldopam, being active in nanomole doses, whereas NE was more potent than DA. Rauwolscine, an alpha-2 adrenoceptor antagonist, antagonized the inhibitory effects of NE and DA and was the only antagonist, given i.a. or i.v., that facilitated ganglionic transmission; frequency-response curves of tachycardia induced by preganglionic nerve stimulation were dose-dependently augmented. SCH 23390, in double the full DA1 antagonist dose, had no effect on frequency-response curves or on NE- or DA-induced ganglionic inhibition. Domperidone antagonized the effect of DA but had no effect on ganglionic inhibition produced by NE or on frequency-response curves of tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS) .A Satoh Y; Kohli JD; Goldberg LI. .I 201927 .U 90011800 .S J Pharmacol Exp Ther 9001; 251(1):258-66 .M Animal; Cocaine/AA/PD; Corpus Striatum/*DE/ME; Dopamine/*PH; In Vitro; Lactates/ME; Male; Mice; NAD/ME; Rats; Support, U.S. Gov't, P.H.S.; Transmitter Uptake Inhibitors, Neuronal/*PD; Tyrosine Hydroxylase/ME; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/*AA/*AI/PD. .T Attenuation by dopamine uptake blockers of the inhibitory effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and some of its analogs on NADH-linked metabolism in mouse neostriatal slices. .P JOURNAL ARTICLE. .W In previous studies it was shown that the pyridinium species formed by the monoamine-oxidase-catalyzed conversion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-(2'methylphenyl)-1,2,3,6-tetrahydropyridine (2'Me-MPTP) inhibited mitochondrial electron transport at Complex I. In addition, these substances, when incubated with mouse neostriatal slices, caused an increased lactate accumulation. However, it was not clear whether this inhibition could occur within dopamine nerve terminals. In the present study we investigated if dopamine uptake blockers, shown previously to protect against tetrahydropyridine-induced dopaminergic neurotoxicity, would attenuate MPTP- and 2'Me-MPTP-promoted lactate formation in neostriatal slices. 2'Me-MPTP-induced lactate accumulation in neostriatal slices from mice or rats with a lesion of the nigrostriatal pathway was also studied. The dopamine uptake blocker, Win 35,428 [8-azabicyclo[3.2.1]octane-2-carboxylic acid, 3-(4-fluorophenyl)-8-methyl-, methylester [1R-(exo, exol)]), attenuated the increased lactate formation caused by MPTP and 2'Me-MPTP. At low concentrations of 2'Me-MPTP (5 microM), the increased lactate production was inhibited completely by Win 35,428. These latter data suggest that at low concentrations of 2'Me-MPTP, the increased lactate accumulation was associated primarily with dopaminergic nerve terminals. Two other dopamine uptake inhibitors, McN 5908 [trans-4-(1,2,3,5,6,10b-hexahydropyrrolo[2,1-alpha]isoquinolin+ ++-6-yl) benzenamine hydrobromide methanolate (4:4:1)] and mazindol [5-(4-chlorophenyl)-2,5-dihydro-3H-imidazo- [2,1-alpha]isoindol-5-ol], also attenuated tetrahydropyridine-induced lactate formation. At concentrations selective for their respective uptake systems, norepinephrine- and serotonin-uptake inhibitors did not attenuate 2'Me-MPTP-induced lactate accumulation.(ABSTRACT TRUNCATED AT 250 WORDS) .A Ofori S; Heikkila RE; Nicklas WJ. .I 201928 .U 90011801 .S J Pharmacol Exp Ther 9001; 251(1):267-71 .M Analgesics/*PD; Animal; Male; Mice; Pyrrolidines/*PD; Rats; Receptors, Endorphin; Spinal Cord/*DE. .T Spinal analgesic actions of kappa receptor agonists, U-50488H and spiradoline (U-62066). .P JOURNAL ARTICLE. .W Administered i.p. to mice, the selective kappa receptor agonists U-50488H and spiradoline (U-62066) were more potent on the tail-flick than on the hot-plate analgesic assay. Both were more potent after i.s. rather than i.c. administration, a result consistent with earlier demonstrations that tail-flick analgesia is generally dependent upon spinal mechanisms. Intraspinal U-50488H was not effective in elevating rat tail-flick latencies. Both drugs increased the thresholds for cat spinal cord nociceptive neurons to respond to a noxious heat stimulus. However, maximal responses of spinal cord neurons to nociceptive stimuli were not altered. It is concluded that although spinal cord sites may be critical to kappa receptor analgesic mechanisms, the effects are quite distinct from spinal cord effects observed previously with classical narcotic analgesics. .A Piercey MF; Einspahr FJ. .I 201929 .U 90011802 .S J Pharmacol Exp Ther 9001; 251(1):27-38 .M Adrenergic Alpha Receptor Blockaders/PD; Analgesics/*PD; Animal; Blood Pressure/*DE; Clonidine/AD/*PD/PK; Dose-Response Relationship, Drug; Heart Rate/*DE; Injections, Spinal; Male; Phentolamine/PD; Rats; Rats, Inbred Strains; Receptors, Adrenergic, Alpha/DE/*PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tissue Distribution. .T Pharmacological characterization of alpha adrenoceptors involved in the antinociceptive and cardiovascular effects of intrathecally administered clonidine. .P JOURNAL ARTICLE. .W The effects on nociception, blood pressure and heart rate of clonidine administered intrathecally to the lumbar level were determined in conscious rats and in rats anesthetized lightly with pentobarbital. In anesthetized rats, intrathecal (i.t.) clonidine (3.2-32.0 micrograms) inhibited the nociceptive tail-flick reflex and had biphasic effects on blood pressure; lesser doses (1.0-10.0 micrograms) produced depressor effects, whereas a greater dose (32.0 micrograms) produced a marked pressor response. Clonidine also produced biphasic effects on blood pressure in conscious rats, with the dose-response function shifted upward and to the left of that observed in anesthetized rats. The depressor and antinociceptive effects of 3.2 micrograms of clonidine were antagonized by pretreatment with yohimbine (30.0 micrograms i.t.) but not by prazosin (30.0 micrograms i.t.) or by yohimbine (0.1 mg/kg i.v.). Thus, these effects of clonidine are mediated by spinal alpha-2 adrenoceptors. The pressor response to 32.0 micrograms of clonidine (i.t., lumbar) was accompanied by marked bradycardia, and similar cardiovascular effects were observed when this dose of clonidine was administered either i.v. or to the cervical level of the spinal cord. The pressor response to 32.0 micrograms of clonidine (i.t., lumbar) was not reduced significantly by i.t. pretreatment with yohimbine (30.0 micrograms) or prazosin (30.0 micrograms), but was diminished significantly by i.v. pretreatment with yohimbine (1.0 mg/kg), prazosin (0.1 mg/kg) or phentolamine (2.0 mg/kg). Neither chlorisondamine (2.5 mg/kg i.v.) or the V1-vasopressin receptor antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(o-methyl)tyrosine]Arg8-vasopressin (10.0 micrograms/kg i.v.) reduced the clonidine-produced pressor response. After i.t. injection of 32.0 micrograms of [3H]clonidine, peak levels of radioactivity in the blood were observed at 2 min and corresponded to a blood concentration of 38.8 ng/ml. Injection of an i.v. bolus dose (2.5 micrograms/kg) sufficient to produce these blood levels resulted in a transient pressor response. These results suggest that after i.t. administration of greater doses of clonidine, sufficient amounts of the drug are rapidly redistributed systemically to produce pressor effects by stimulation of vascular alpha adrenoceptors. .A Solomon RE; Brody MJ; Gebhart GF. .I 201930 .U 90011803 .S J Pharmacol Exp Ther 9001; 251(1):272-8 .M Amiodarone/*TO; Animal; Cattle; Cells, Cultured; Endothelium, Vascular/DE; Lung/*DE/ME; Lysosomes/DE/EN; Microsomes/DE/EN; Phospholipases/*ME; Phospholipases A/*ME; Phospholipids/*ME; Pulmonary Artery/DE; Support, U.S. Gov't, P.H.S.. .T Mechanism of phospholipidosis in amiodarone pulmonary toxicity. .P JOURNAL ARTICLE. .W Amiodarone therapy can be complicated by life-threatening pulmonary toxicity and is invariably associated with characteristic morphologic changes in the lung consistent with a severe phospholipidosis. To determine possible mechanisms, this study utilizes a unique in vitro cell culture model of amiodarone pulmonary toxicity and demonstrates that amiodarone can directly induce an accumulation of phospholipids within bovine pulmonary artery endothelial (BPAE) cells during the first 24 hr using amiodarone concentrations equivalent to concentrations found in the blood and lungs of human subjects. For example, amiodarone at 7.5 microM during a 24-hr incubation increases [32P]orthophosphate incorporation into phospholipids from 193 +/- 10 X 10(3) dpm/10(6) cells to 266 +/- 19 X 10(3) dpm/10(6) cells (P less than .01). A generalized increase in all phospholipids occurs after amiodarone treatment of the cultured cells; however, several specific phospholipids including phosphatidylinositol, phosphatidic acid and bis(monoacylglycerol) phosphate are all significantly increased to a greater extent than other phospholipids. Furthermore, the data indicate that amiodarone is a potent inhibitor of lysosomal phospholipase A1 and A2 activities derived from the BPAE cells; whereas, amiodarone has no effect on phospholipase A1 and A2 activities from the BPAE microsomal fraction. Thus, this study demonstrates phospholipids accumulate in cultured BPAE cells exposed to amiodarone and provides direct evidence that the drug initiates a specific and nearly complete inhibition of phospholipid degradation by lysosomal phospholipase A1 and A2 suggesting a similar process may occur in vivo in the lungs of subjects with amiodarone pulmonary toxicity. .A Martin WJ 2d; Kachel DL; Vilen T; Natarajan V. .I 201931 .U 90011804 .S J Pharmacol Exp Ther 9001; 251(1):279-87 .M Adenosine/*AA/PD; Animal; Biological Transport/DE; Erythrocytes/DE; Female; Guinea Pigs; In Vitro; Receptors, Purinergic/*DE; Swine; Uridine/*ME; Vasodilation/DE. .T Effects of adenosine A2 receptor agonists on nucleoside transport. .P JOURNAL ARTICLE. .W A series of adenosine A2 receptor agonists were examined for their ability to activate adenosine A2 receptors and inhibit nucleoside transport. A2 receptor activation was measured by the ability of these adenosine agonists to relax porcine coronary smooth muscle, where the compounds varied in their EC50 values from 4.5 nM (CGS 21680A (2-[p-(2-carboxyethyl) phenylethylamino]-5'-N-ethylcarboxamidoadenosine)] to 3.6 microM (CGS 23321 [2 alpha,3 alpha-dihydroxy-1 beta-hydroxymethyl-4 beta-(2-phenylamino-9- adenyl)-cyclopentane]). Nucleoside transport was measured as the nitrobenzylthioinosine-sensitive cellular accumulation of [3H]uridine into guinea pig erythrocytes at 22 degrees C. The initial velocity of transport was dependent on substrate concentration and a substrate-velocity curve yielded a Km of 78 +/- 16 microM and a Vmax of 0.31 +/- 0.049 mmol/l of cell water per hr (mean +/- S.D., n = 4). Dipyridamole, a known potent inhibitor of nucleoside transport, blocked cellular [3H]uridine accumulation with an EC50 of 29.4 nM. Whereas a number of the adenosine agonists tested showed little or no inhibition of nucleoside transport, CV 1808 (2-phenylaminoadenosine) inhibited transport with an EC50 of 140 nM. In addition, two carbocyclic derivatives of CV 1808, CGS 23321 and CGS 23302 [(-)2S,3R-dihydroxy-4R-hydroxymethyl-1R-[2-(p-ethoxycarbonyl)- phenylamino-9-adenyl]-cyclopentane) inhibited nucleoside transport with respective EC50 values of 366 and 168 nM. The data suggest that these compounds have a different structure-activity relationship for adenosine A2 receptors and for the site mediating nucleoside transport inhibition. .A Balwierczak JL; Krulan CM; Wang ZC; Chen J; Jeng AY. .I 201932 .U 90011805 .S J Pharmacol Exp Ther 9001; 251(1):288-94 .M Animal; Diphenylacetic Acids/PK; Disease Models, Animal; Glucuronates/*ME; Kidney Diseases/CI/*ME; Male; Rabbits; Support, Non-U.S. Gov't; Uranyl Nitrate. .T Effect of renal dysfunction on the individual components of the acyl-glucuronide futile cycle. .P JOURNAL ARTICLE. .W Drugs which are cleared predominantly by forming acyl-glucuronides undergo a futile cycle in which plasma drug clearance is a function of the formation, hydrolysis and renal clearance of the glucuronide conjugate. The effect of impaired renal function, induced by uranyl nitrate administration, on each component of this process was studied in rabbits using diphenylacetic acid. Uranyl nitrate administration produced a decrease in creatinine clearance of approximately 70% and diphenylacetic acid plasma clearance of approximately 35%. In healthy rabbits the primary determinant of diphenylacetic acid net clearance was the very large component of glucuronide renal clearance (14.10 ml/min/kg) compared with glucuronide formation (4.79 ml/min/kg) or glucuronide hydrolysis (2.56 ml/min/kg). Uranyl nitrate treatment reduced both creatinine clearance and the glucuronide renal clearance by approximately 70%. Renal dysfunction had little effect on the hydrolysis clearance of the glucuronide, but reduced its formation clearance by 22.8%. The reduction in plasma clearance of diphenylacetic acid was a function of both the decrease in glucuronidation (60% contribution) and the decrease in renal clearance of the glucuronide (40% contribution). This study supports the futile cycle mechanism of reversible glucuronide conjugation for acyl-glucuronides in general, and provides a mechanism for the impairment of the plasma clearance in renal failure of drugs forming acyl-glucuronides. .A Sallustio BC; Purdie YJ; Birkett DJ; Meffin PJ. .I 201933 .U 90011807 .S J Pharmacol Exp Ther 9001; 251(1):305-10 .M Adenyl Cyclase/ME; Adrenergic Beta Receptor Blockaders/ME; Animal; Binding, Competitive; Dogs; Ileum/*IR; In Vitro; Muscle, Smooth/EN/ME; Myenteric Plexus/ME; Pindolol/AA/ME; Radioligand Assay; Receptors, Adrenergic, Beta/*ME; Subcellular Fractions/ME; Support, Non-U.S. Gov't. .T Identification and characterization of presynaptic and postsynaptic beta adrenoreceptors in the longitudinal smooth muscle/myenteric plexus of dog ileum. .P JOURNAL ARTICLE. .W The subcellular distribution of [125I]cyanopindolol (125I-CYP) binding in membrane fractions derived from the longitudinal smooth muscle/myenteric plexus (LSM/MP) of dog ileum followed a bimodal pattern with selective enrichments in the purified synaptosomal (S2) fraction and the purified smooth muscle plasma membrane (M2) fraction. The half-maximal saturation of binding sites in both fractions occurred at 10 pM [125I]CYP with maximal binding capacities, in femtomoles per milligram of protein, 70 +/- 10 (S2 fraction) and 110 +/- 25 (M2 fraction). Approximately 80% of binding sites in either membrane fraction exhibited a high affinity for beta-2 selective antagonist ICI 118,551 (Ki = 1.4 +/- 0.4 nM in S2 and 1.8 +/- 0.6 nM in M2; mean +/- S.D. n = 3), whereas remaining 20% of binding sites had a low affinity for this agent (Ki = 2.6 +/- 1.5 microM in S2 and 0.55 +/- 0.2 microM in M2). The beta-1-selective antagonist ICI 89,406 had a high affinity for approximately 20% of binding sites (Ki = 12 +/- 7 nM in S2 and 4 +/- 2 nM in M2) and a low affinity for approximately 80% of binding sites (Ki = 0.34 +/- 0.16 microM in S2 and 0.42 +/- 0.24 microM in M2). The displacement potencies of beta-adrenergic agonists followed the order (-)-isoproterenol greater than salbutamol (-)-epinephrine greater than (-)-norepinephrine in each membrane preparation. The inclusion of 0.1 mM 5'-guanylylimidodiphosphate into assay medium resulted in a decreased affinity of receptors for agonists and increased values of Hill coefficients.(ABSTRACT TRUNCATED AT 250 WORDS) .A Kostka P; Sipos SN; Kwan CY; Niles LP; Daniel EE. .I 201934 .U 90011808 .S J Pharmacol Exp Ther 9001; 251(1):311-6 .M Amphotericin B/*AD/PK/TO; Animal; Drug Carriers; Glomerular Filtration Rate/DE; Kidney Diseases/*CI/EN; Kidney Tubules/DE; Liposomes; Male; Rabbits. .T Incorporation of amphotericin B (AMB) into liposomes alters AMB-induced acute nephrotoxicity in rabbits. .P JOURNAL ARTICLE. .W To investigate the protective effect of liposomes on acute amphotericin B (AMB) renal toxicity, we compared in rabbits the acute toxicity of 4 mg/kg of free-AMB and 4 or 10 mg/kg of liposomal AMB (L-AMB) during 90 min after antibiotic infusion. Free-AMB exhibited immediate nephrotoxicity with a 44% decrease of the glomerular filtration rate and alteration of tubular cell membrane permeability expressed as increases in urinary pH (6.5 vs. 4.7), potassium fractional excretion (95% vs. 30%) and sodium fractional excretion (26% vs. 4%). Urinary excretion of the lysosomal enzyme N-acetylglucosaminidase was unchanged by free-AMB. Incorporation of AMB into liposomes prevented the toxic effects of free-AMB on glomerular filtration and tubular cells membrane, but significantly increased N-acetylglucosaminidase urinary excretion (380 and 180% in animals receiving 4 and 10 mg/kg of L-AMB, respectively). Absolute AMB urinary excretion during the experiment was unchanged by liposomes and was always less than 1% of the total dose administered. Liposomes alone exhibited no toxicity. These results suggest that liposomes could increase the interaction between AMB and lysosomes leading to an additional mechanism of cellular injury. They admonish close monitoring of renal function and enzymuria in clinical situations in which L-AMB is being used. .A Joly V; Dromer F; Barge J; Yeni P; Seta N; Molas G; Carbon C. .I 201935 .U 90011809 .S J Pharmacol Exp Ther 9001; 251(1):317-20 .M Angiotensin I/*PD; Angiotensin II/*PD; Animal; Cerebral Arteries/*DE; Dogs; Drug Interactions; Endothelium, Vascular/*PH; Female; In Vitro; Male; Support, Non-U.S. Gov't; Vasoconstriction/*DE. .T Endothelium-dependent contractions induced by angiotensin I and angiotensin II in canine cerebral artery. .P JOURNAL ARTICLE. .W Whether angiotensin I and angiotensin II caused endothelium-dependent contraction was examined in canine cerebral arteries. In endothelium-intact preparations, angiotensin I and angiotensin II at 10(-8) to 10(-6) M caused dose-dependent contractions, whereas both angiotensins caused much less contractions in endothelium-removed preparations. The contractions induced by angiotensin I and angiotensin II were strongly attenuated by aspirin (cyclooxygenase inhibitor) (5 x 10(-5) M), OKY-046 [thromboxane (TX) A2 synthetase inhibitor] (10(-5) M) and ONO-3708 (TX)A2 antagonist) (5 X 10(-9) M). Captopril (10(-6) M) significantly attenuated the contractions induced by angiotensin I but not those induced by angiotensin II. Angiotensin I- and angiotensin II- induced contractions were inhibited markedly by Sar1, Ala8-angiotensin II (10(-9) and 10(-8) M). The present experiments demonstrate that angiotensin I and angiotensin II produce endothelium-dependent contraction in canine cerebral artery via a factor which appears to be TXA2. Angiotensin I may be converted by endothelial cells to angiotensin II, which may activate the cells to produce TXA2 in canine cerebral artery. .A Manabe K; Shirahase H; Usui H; Kurahashi K; Fujiwara M. .I 201936 .U 90011812 .S J Pharmacol Exp Ther 9001; 251(1):334-41 .M Analgesics, Addictive/*PD; Animal; Comparative Study; Electric Stimulation; Heat; Male; Narcotic Antagonists/PD; Pressure; Rats; Rats, Inbred Strains; Receptors, Endorphin; Support, Non-U.S. Gov't. .T Kappa-opioid receptor-mediated antinociception in the rat. I. Comparative actions of mu- and kappa-opioids against noxious thermal, pressure and electrical stimuli. .P JOURNAL ARTICLE. .W This study examined the comparative efficacy of mu- and kappa-opioids in modulating the tail-withdrawal response to matched intensity heat and pressure stimuli and the vocalization response to electrical stimulation in the rat. All drugs were given s.c. The mu-agonists, morphine and fentanyl, were equipotent against heat and pressure at all intensities. The kappa-agonists, U50,488H and U69,593 also acted against pressure in an intensity-independent fashion. However, their action against heat was intensity-dependent being greatest against "low" and least against "high" intensity. At "moderate" intensities, morphine, fentanyl, U69,593, U50,488H and 2 other kappa-agonists (bremazocine and tifluadom) were equipotent against heat and pressure. The action of tifluadom was stereospecific. Naltrexone (a preferential mu-antagonist) was 10 times more potent in blocking the actions of morphine and fentanyl (as compared to U69,593 and U50,488H) against both heat and pressure. The preferential kappa-antagonists, nor-binaltorphimine and MR 2266, were 5- and 2-fold, respectively, more potent against the kappa-ligands for both heat and pressure. The antagonism of MR 2266 was expressed stereospecifically. Fentanyl and morphine induced a powerful antinociception against electrical stimulation whereas U69,593, U50,488H, bremazocine and tifluadom were completely inactive. Thus, kappa-opioid receptors can mediate antinociception against noxious thermal stimuli. However, in contrast to mu-receptors, this antinociception against heat is intensity-dependent. Kappa-agonists, in distinction to mu-agonists, are inactive against electrical stimulation. .A Millan MJ. .I 201937 .U 90011813 .S J Pharmacol Exp Ther 9001; 251(1):342-50 .M Analgesics, Addictive/*PD; Animal; Brain/*DE; Male; Morphine/PD; Narcotic Antagonists/PD; Pyrrolidines/PD; Rats; Rats, Inbred Strains; Receptors, Endorphin; Spinal Cord/*DE; Support, Non-U.S. Gov't. .T Kappa-opioid receptor-mediated antinociception in the rat. II. Supraspinal in addition to spinal sites of action. .P JOURNAL ARTICLE. .W This study examines whether there is a supraspinal, in addition to spinal, component to the antinociceptive actions against heat and pressure stimuli of kappa-opioid receptor agonists (U-69,593, U50,488H, bremazocine and tifluadom) as compared to mu-opioid receptor agonists (Tyr-D-Ala-Gly-NMe-Gly-ol, fentanyl and morphine) in the rat. The antinociception induced by kappa- and mu-opioids (applied s.c.) was unaffected by systemic quaternary naltrexone (50 mg/kg) revealing that it is mediated in the central nervous system. All kappa- and mu-opioids produced dose-dependent antinociception upon intrathecal application, in each case reversible by naloxone (5 mg/kg s.c.). However, intrathecal application of naloxone could only partially (by ca. 50%) antagonize the antinociception evoked by systemically applied U50,488H and morphine: this suggests sites of action in brain in addition to spinal cord for both mu- and kappa-opioids. Intraventricular application of mu-agonists produced maximal, dose-dependent antinociception. All kappa-agonists were also active in producing dose-dependent antinociception although curves were shallow and maximal antinociception could not be attained. The action of tifluadom was shown to be stereospecific. Naltrexone was 10-fold more potent in blocking morphine as compared to U50,488H whereas nor-binaltorphimine, a preferential kappa-antagonist, was 6-fold more potent against U50,488H than morphine. Indeed, whereas a dose of 0.2 mg/kg of naltrexone reversed mu-agonist actions, this dose was inactive against all kappa-agonists: the actions of these could be antagonized only by 2.0 mg/kg. These data indicate that in addition to kappa-receptors in the spinal cord, kappa-receptors in the brain can mediate antinociception against noxious heat and pressure. .A Millan MJ; Czlonkowski A; Lipkowski A; Herz A. .I 201938 .U 90011814 .S J Pharmacol Exp Ther 9001; 251(1):351-7 .M Animal; Arsenicals/PD; Blood-Brain Barrier/*PH; Brain/BS/DE/*ME; Capillaries/ME; Cattle; Chromatography, High Pressure Liquid; Dynorphin/*AA/PK; Endocytosis; In Vitro; Male; Peptide Fragments/*PK; Peptides/PD; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't. .T Absorptive-mediated endocytosis of a dynorphin-like analgesic peptide, E-2078 into the blood-brain barrier. .P JOURNAL ARTICLE. .W The binding and internalization of a novel analog of dynorphin-like analgesic basic peptide, [125I]E-2078 (CH3-[125I] Tyr-Gly-Gly-Phe-Leu-Arg-CH3Arg-D-Leu-NHC2H5), by isolated bovine brain capillaries were investigated. High-performance liquid chromatographic analysis showed that no significant metabolism of [125I] E-2078 occurred during incubation with brain capillaries for 30 min at 37 degrees C. The binding of [125I]E-2078 to brain capillaries increased with time and the steady-state cell-to-medium concentration ratio was 58.5 +/- 2.6 microliters/mg of protein. Approximately one-fourth of the [125I]E-2078 binding was resistant to acid wash, and showed significant dependence on temperature and medium osmolarity. The acid sensitive binding of [125I]E-2078, which presumably represents surface binding, was saturable and the Scatchard plot gave a maximal binding capacity Bmax = 147 +/- 29 pmol/mg of protein, and a half-saturation constant (KD) = 4.62 +/- 0.59 microM. Pretreatment of brain capillaries with phenylarsine oxide, an endocytosis inhibitor, completely suppressed the acid resistant binding of [125I]E-2078, but did not influence the surface binding of [125I]E-2078. The acid resistant binding of [125I] E-2078 was inhibited by poly-L-lysine and protamine, but not inhibited by insulin, transferrin, dynorphin (1-8), beta-neoendorphin, naloxone or poly-L-glutamate. Moreover, in vivo brain extraction of [125I]E-2078 in rats was 368 +/- 55% higher than that of [3H] sucrose and was significantly inhibited by 1 mM of unlabeled E-2078. These results demonstrate that E-2078 is internalized by brain capillaries via absorptive-mediated endocytosis, which is a polycation-sensitive pathway. .A Terasaki T; Hirai K; Sato H; Kang YS; Tsuji A. .I 201939 .U 90011815 .S J Pharmacol Exp Ther 9001; 251(1):358-61 .M Animal; Human; Infusions, Intravenous; Macaca mulatta; Male; Recombinant Proteins/PK; Tumor Necrosis Factor/*PK. .T Pharmacokinetics of recombinant human tumor necrosis factor alpha in rhesus monkeys after intravenous administration. .P JOURNAL ARTICLE. .W Recombinant human tumor necrosis factor alpha (TNF-alpha) was administered to rhesus monkeys by i.v. short-term infusions (0.5 hr) of 10, 20, 30 and 120 micrograms/kg and long-term infusions (6.5 hr) of 22, 54, 135 and 325 micrograms/kg. At high plasma levels of TNF-alpha (doses of 120 micrograms/kg of short-term infusions and greater than or equal to 54 micrograms/kg of long-term infusion) the pharmacokinetics of TNF-alpha were practically first order. A plasma T1/2 of 1.2 to 2.1 hr was calculated. However, at low plasma levels (doses of 10-30 micrograms/kg of short-term infusion and 22 micrograms/kg of long-term infusion) the elimination rate increased steadily in dependence on concentration and time. We conclude that at low concentrations of TNF-alpha the pharmacokinetics were not first order. Simultaneous long-term infusion of recombinant human TNF-beta (200 micrograms/kg) in addition to 22 micrograms/kg of TNF-alpha reduces the elimination rate of TNF-alpha, which can be concluded from the elevation of the TNF-alpha plasma levels. Furthermore, there was no time-dependent increase of the elimination rate that was detected without infusion of TNF-beta. Based on these results two different elimination mechanisms of TNF-alpha in rhesus monkeys are postulated: an unspecific, nonsaturable process as well as a specific, saturable mechanism. .A Greischel A; Zahn G. .I 201940 .U 90011816 .S J Pharmacol Exp Ther 9001; 251(1):362-7 .M Animal; Brain/DE/*ME; Clonazepam/ME/PD; Glucose/*ME; Male; Mice; Receptors, GABA-Benzodiazepine/*ME. .T Nonlinear relationship between benzodiazepine receptor occupancy and glucose metabolic response in the conscious mouse brain in vivo. .P JOURNAL ARTICLE. .W To evaluate the relationship between the pharmacological effect of benzodiazepine (BZP) and BZP receptor (BZP-R) binding in the conscious mouse brain, a response of the local cerebral metabolic rate of glucose utilization (GU) to clonazepam (CNZ) was measured as an index for the pharmacological effect. Two glucose analogs (3-O-[3H]methylglucose and 2-[14C]deoxyglucose) method, originally presented by A. Gjedde was used for determination of GU. In the cerebral cortex, GU decreased to 70 to 80% at 60 min after i.v. administration of CNZ (0.005-1.0 mg/kg), but CNZ did not change the lumped constant, and this effect was diminished completely by the administration of a BZP antagonist, Ro-15-1788 (5 mg/kg). The maximum effect of CNZ on GU (about 30% decrease) was found at 0.1 mg/kg of CNZ, but increasing the dose to 1 mg/kg had very little additional effect. In vivo BZP-R occupancy was measured using [3H]-Ro-15-1788. Receptor occupancy increased from less than 10% at a dose of 0.005 mg/kg up to essentially 100% at doses of 1 mg/kg or greater. ID50 in dose-response curve of the receptor occupancy for CNZ and ED50 in that of decrease in GU were 0.3 and 0.007 mg/kg, respectively . A nonlinear and hyperbolic relationship was observed between the receptor occupancy and the response for the glucose metabolic rate, indicating that BZP exert the maximum glucose metabolic change at a low fractional receptor occupancy (30-40%). .A Ishizuka H; Sawada Y; Ito K; Sugiyama Y; Suzuki H; Iga T; Hanano M. .I 201941 .U 90011817 .S J Pharmacol Exp Ther 9001; 251(1):368-71 .M Adolescence; Adult; Antineoplastic Agents/*PD; Cell Division/DE; Cisplatin/PD; Comparative Study; Cyclobutanes/*PD; Human; In Vitro; Lymphocytes/*DE; Male; Naphthoquinones/*PD; Organoplatinum Compounds/*PD; Sister Chromatid Exchange/*DE. .T Comparative study on cytogenetic effects by diplatinum complexes of the ligands of naphthazarine and squaric acid in human lymphocytes. .P JOURNAL ARTICLE. .W The effect of diplatinum complexes of the binucleating ligands of naphthazarine and squaric acid on Sister Chromatid Exchange (SCE) rates and human lymphocyte proliferation kinetics was studied. Squarodicisplatinum complex I, naphthazarindicisplatinum and squarodicisplatinum complex II induce cytotoxic effects as can be deduced from the resulted induction of SCEs and the produced cell division delays. Squarodicisplatinum complex I was found to be on a molar basis the most effective in causing markedly increased SCE rates and cell division delays. Cis-diaminodichloride platinum was found to be next in order of effectiveness with naphthazarindicisplatinum and squarodicisplatinum complex II following. Naphthazarine and SQA were found to be ineffective on induction of SCEs. .A Lialiaris T; Mourelatos D; Boutis L; Papageorgiou A; Christianopoulou M; Papageorgiou V; Dozi-Vassiliades J. .I 201942 .U 90011820 .S J Pharmacol Exp Ther 9001; 251(1):388-93 .M Amino Acid Sequence; Animal; Comparative Study; Dose-Response Relationship, Drug; Male; Molecular Sequence Data; Motor Activity/*DE; Raphe Nuclei/DE; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't; Tachykinins/*PD. .T A dose-response analysis of intra-raphe tachykinin-induced hyperactivity. .P JOURNAL ARTICLE. .W The nonmammalian (eledoisin, kassinin and physalaemin) and mammalian tachykinins (substance P and neurokinin (NK) A), as well as the metabolically stable neurokinin analogs, DiMe-C7 [( pGlu5, MePhe8, Sar9]substance P (5-11)] and senktide, were infused into the median raphe nucleus of rats via chronically implanted cannulas, and their effects on locomotor activity analyzed. The NK-3 receptor agonists, senktide and DiMe-C7, as well as the endogenous NK-2 receptor ligand, NKA, produced dose-dependent increases in locomotor activity. Substance P, eledoisin, kassinin and physalaemin elevated activity but not dose-dependently. Regression analyses demonstrated that senktide and DiMe-C7 were the most potent and efficacious of the peptides tested. The slopes of the senktide and DiMe-C7 dose-response curves were parallel and differed significantly from the slope of the NKA dose-response curve. Infusions of the endogenous NK-3 ligand, NKB (3.0 pmol in 1.0 microliter), also elicited hyperactivity equivalent to that produced by an equimolar dose of senktide. These and previous findings suggest that activation of NK-2 and NK-3 receptors in the midbrain raphe leads to behavioral arousal through their influence on serotonin neurons. .A Paris JM; Lorens SA. .I 201943 .U 90011821 .S J Pharmacol Exp Ther 9001; 251(1):39-46 .M Action Potentials/DE; Animal; Anti-Arrhythmia Agents/*PD; Dogs; Female; Heart/*DE; Heart Conduction System/DE; Heart Ventricle/DE; Lidocaine/PD; Male; Mexiletine/PD; Quinidine/PD; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Frequency-dependent antiarrhythmic drug effects on postrepolarization refractoriness and ventricular conduction time in canine ventricular myocardium in vivo. .P JOURNAL ARTICLE. .W Both conduction time (CT) and effective refractory period (ERP), absolute and relative to action potential duration (APD), are major determinants of re-entry arrhythmia circuits. We compared the effects of 3 commonly used class I antiarrhythmic agents, lidocaine, mexiletine and quinidine, and of the combination of the latter 2, on APD, ERP, ERP/APD ratio and interventricular CT in 26 in vivo canine hearts. To assess also the frequency dependence of these effects, each measurement was made at multiple steady-state cycle lengths ranging from 600 to 250 msec. A modified contact electrode technique was used to measure both APD and ERP simultaneously and at the same left ventricular site. Interventricular CT was measured as the interval from the stimulus of right ventricular paced beats to the upstroke of the ensuing left ventricular action potential. Lidocaine did not change APD, ERP and ERP/APD ratio significantly at any basic cycle length. In contrast, both mexiletine and quinidine increased the ERP/APD ratio, with progressively greater effects toward shorter cycle lengths. The quinidine/mexiletine combination increased the ERP/APD ratio significantly more than either drug alone (cycle length 350 msec: 8.3 +/- 2.2% quinidine; 17.6 +/- 7.0% mexiletine; 35.3 +/- 9.6% mexiletine/quinidine combination, P less than .01 vs. quinidine, P less than .05 vs. mexiletine). CT increased only with quinidine but not with mexiletine or lidocaine. Combination of mexiletine and quinidine caused no further slowing of conduction as compared to quinidine alone. Thus, although both ERP/APD ratio and CT are related to sodium channel conductance, drug effect on one parameter does not necessarily imply quantitatively similar effects on the other.(ABSTRACT TRUNCATED AT 250 WORDS) .A Costard-Jackle A; Franz MR. .I 201944 .U 90011822 .S J Pharmacol Exp Ther 9001; 251(1):47-55 .M Adenosine/PD; Animal; Antihypertensive Agents/*PD; Blood Pressure/DE; Comparative Study; Heart/*DE; Heart Rate/DE; In Vitro; Male; Phenethylamines/*PD; Radioligand Assay; Rats; Rats, Inbred Strains; Rats, Inbred SHR; Receptors, Purinergic/DE. .T CGS 21680C, an A2 selective adenosine receptor agonist with preferential hypotensive activity. .P JOURNAL ARTICLE. .W CGS 21680C (2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethyl-carboxamido adenosine) a 2-substituted analog of the riboside uronamide, 5'-N-ethylcarboxamido adenosine and the related analog CGS 21577 (2-phenethylamino-5'-N-ethylcarboxamido adenosine), have high in vitro affinity for brain striatal adenosine A2 receptors (IC50 values = 22 and 13 nM, respectively). Both compounds were considerably less active at A1 receptors with CGS 21577 and CGS 21680C having respective IC50 values of 0.76 and 3.1 microM. The former compound was thus 59-fold selective for A2 receptors whereas CGS 21680C was 140-fold selective. In contrast, the reference A2 selective ligand, CV 1808 (2-phenylaminoadenosine), showed only 8-fold selectivity as an A2 ligand, having an IC50 of 115 nM in the [3H]-5'N-ethylcarboxamide adenosine assay and an IC50 of 910 nM at the N6-[3H] cyclohexyladenosine site. Further examination of CGS 21680C showed that the compound was without effect on binding to 17 other putative neurotransmitter/neuromodulator sites indicating its selectivity as an adenosine receptor ligand. In an isolated perfused working rat heart model, CGS 21680C effectively increased coronary flow with an ED25 value of 1.8 nM. The corresponding value for CGS 21577 was 3 nM whereas that for CV 1808 was 110 nM. The EC25 for eliciting bradycardia for all three compounds was greater than 1000 nM. The effects of all three compounds could be reversed by treatment with the xanthine adenosine antagonist, xanthine amine congener.(ABSTRACT TRUNCATED AT 250 WORDS) .A Hutchison AJ; Webb RL; Oei HH; Ghai GR; Zimmerman MB; Williams M. .I 201945 .U 90011823 .S J Pharmacol Exp Ther 9001; 251(1):56-62 .M Amphetamine/*PD; Animal; Cocaine/*PD; Comparative Study; In Vitro; Membrane Potentials/DE; Neurons/DE; Prazosin/PD; Raphe Nuclei/*DE; Rats; Serotonin/PH; Spiperone/PD; Support, U.S. Gov't, P.H.S.. .T Differential actions of cocaine and amphetamine on dorsal raphe neurons in vitro. .P JOURNAL ARTICLE. .W Intracellular recordings of membrane potential were made from neurons in nucleus dorsal raphe in the rat brain slice. Cocaine (300 nM-30 microM) caused a concentration-dependent hyperpolarization of the membrane potential, with a maximum effect of 13.3 +/- 2.2 mV (N = 6) and an EC50 of 4.2 microM. This action was antagonized by spiperone (1 microM), suggesting that the hyperpolarization was mediated indirectly through endogenous 5-hydroxytryptamine (5-HT). Cocaine (300 nM) increased the time constant for decay (tau 2) of the 5-HT inhibitory postsynaptic potential (IPSP) from 432 +/- 57 msec to 708 +/- 81 msec (N = 14); 10 microM increased tau 2 by about 9-fold. Amphetamine (100 nM-10 microM) caused a depolarization that was antagonized by prazosin (100 nM). In slices taken from reserpine-treated animals (5 mg/kg, 12 hr), the 5-HT-mediated IPSP, the noradrenaline-mediated slow excitatory postsynaptic potential and the amphetamine-induced depolarization were absent. These results indicate that the amphetamine-induced depolarization resulted from the release of endogenous noradrenaline. In the presence of prazosin (100 nM), amphetamine caused a hyperpolarization at a threshold concentration of 10 microM, had an EC50 of 26 microM and a maximum effect of 10 +/- 0.9 mV (N = 8). This hyperpolarization as well as the cocaine-induced hyperpolarization were not reduced by prior treatment with reserpine. Amphetamine (10 microM) caused a 2.2-fold increase in the time constant of decay of the IPSP with no change in the amplitude.(ABSTRACT TRUNCATED AT 250 WORDS) .A Pan ZZ; Williams JT. .I 201946 .U 90011824 .S J Pharmacol Exp Ther 9001; 251(1):63-70 .M Adenosine Triphosphate/*PH; Centrifugation, Density Gradient; Human; Parasympatholytics/PD; Parasympathomimetics/ME/*PD; Radioligand Assay; Receptors, Muscarinic/DE/*ME; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured/ME. .T Evidence for an agonist-induced, ATP-dependent change in muscarinic receptors of intact 1321N1 cells. .P JOURNAL ARTICLE. .W The binding of muscarinic agonists, partial agonists and antagonists to muscarinic receptors of intact 1321N1 human astrocytoma cells and of cell lysates was studied. Partial agonists and antagonists exhibited similar apparent affinities in intact cell competition binding assays with either the lipophilic radioligand [3H]quinuclidinyl benzilate [( 3H]QNB) or the hydrophilic radioligand [3H]N-methyl scopolamine [( 3H]NMS). In contrast, full agonists exhibited markedly lower apparent affinities in intact cell competition binding assays with [3H]QNB than with [3H]NMS. The affinities of agonists and antagonists in competition for [3H] NMS binding to intact cells were slightly higher than those observed in competitions for [3H]QNB binding in cell lysates. In contrast, the affinities of agonists in competition for [3H]QNB binding to intact cells were considerably lower than those in competition for [3H]QNB binding in cell lysates. Treatment of cells with antimycin A to deplete intracellular ATP prevented agonist-induced internalization of muscarinic receptors as assessed by sucrose density gradient assays of receptor subcellular distribution. In ATP-depleted cells, the apparent affinities of full agonists vs. [3H]QNB were markedly higher and were similar to their apparent affinities vs. [3H]QNB in cell lysates. The apparent affinities of partial agonists and of antagonists were unaffected by ATP depletion. ATP depletion decreased slightly the apparent affinity of the full agonist carbachol in competition for [3H]NMS binding to intact cells, whereas the apparent affinity of atropine was unchanged. These results provide evidence for an agonist-specific, ATP-dependent low affinity state of intact cell muscarinic receptors that may be similar to those observed previously for both beta and alpha-1 adrenergic receptors and that may be related to receptor internalization/sequestration. .A Hoover RK; Toews ML. .I 201947 .U 90011825 .S J Pharmacol Exp Ther 9001; 251(1):71-6 .M Animal; Body Water/SE; Cholera Toxin/*PD; Dogs; Electrolytes/ME; Intestinal Secretions/*DE; Ketanserin/PD; Serotonin/*PH; Support, Non-U.S. Gov't; Verapamil/PD. .T The role of serotonin in the canine secretory response to cholera toxin in vivo. .P JOURNAL ARTICLE. .W This study was initiated to evaluate the role of serotonin in cholera toxin-induced jejunal secretion of water and electrolytes. Chronic Thiry-Vella loops, constructed in six dogs, were perfused with an isosmotic neutral perfusate containing [14C]polyethylene glycol as the recovery marker. Fluxes of water, sodium, chloride and potassium were calculated and immunoreactive serotonin levels were measured in blood and effluent perfusates. Intraluminal application of 20 micrograms of cholera toxin induced secretion; fluxes of water (basal, 32.3 +/- 11.1; 6 hr, -541 +/- 35 microliter/min), sodium (basal, 9.0 +/- 2.8; 6 hr, -78.3 +/- 5.6 microEq/min), chloride (basal, 3.8 +/- 1.5; 6 hr, -65.7 +/- 4.0 muEq/min) and potassium (basal, 0.10 +/- 0.08; 6 hr, -2.80 +/- 0.18 muEq/min) were all significantly different from basal. Serum electrolytes remained normal, except that potassium fell from 4.9 +/- 0.5 to 3.9 +/- 0.2 mEq/l. Although circulating serotonin levels did not change from base line (180.9 +/- 29.3 ng/ml), effluent concentrations increased significantly from 68.2 +/- 4.6 to 81.1 +/- 5.0 ng/ml (at 3 hr) and jejunal outputs increased from 136.6 +/- 10.2 to 205.1 +/- 10.1 ng/min (at 6 hr). In a separate set of experiments, verapamil was infused i.v. (12.5 micrograms/kg/min) during the 4th hr in four dogs exposed to cholera toxin. The lower dose of toxin (5 micrograms) induced secretion which was unaffected by the calcium channel blocker. In another series of studies, ketanserin (a 5-HT2 receptor blocker) was infused i.v. at 33 micrograms/kg/min during the 4th hr in four additional dogs exposed to the lower dose of cholera toxin. This potent serotonin antagonist failed to inhibit cholera toxin-induced jejunal secretion.(ABSTRACT TRUNCATED AT 250 WORDS) .A LaRosa CA; Sherlock D; Kimura K; Pimpl W; Money SR; Jaffe BM. .I 201948 .U 90011827 .S J Pharmacol Exp Ther 9001; 251(1):82-9 .M Ammonium Compounds/*PD; Animal; Arteries/AH/DE; Dogs; Free Radicals; Guanyl Cyclase/ME; In Vitro; Ion Exchange; Membrane Potentials/DE; Support, U.S. Gov't, P.H.S.; Vasodilation/*DE. .T Ammonium ions cause relaxation of isolated canine arteries. .P JOURNAL ARTICLE. .W Experiments were designed to determine the mechanism of action underlying relaxation of vascular smooth muscle induced by ammonium ions. In particular, the possibility that these ions might be an endothelium-derived relaxing factor was examined. Rings of large canine femoral, mesenteric and coronary arteries and of small arteries from the gracilis muscle were suspended in organ chambers for the recording of isometric force. Membrane potential was recorded with intracellular microelectrodes in smooth muscle cells from the mesenteric artery. Ammonium ions induced relaxation which were independent of the presence of the endothelium. The relaxations were not prevented by adrenergic, serotonergic, muscarinic and histaminic blockers, by scavengers of oxygen-derived radicals or by inhibitors of soluble guanylate cyclase. The relaxations were prevented by a decrease in extracellular calcium concentration and by inhibition of the Na+/K+ pump. The results are compatible with the hypothesis that the relaxation induced by ammonium ions is related to changes in intracellular pH and, at high concentration of these ions, possibly to activation of the Na+/K+ pump. Ammonium ions are neither the endothelium-derived relaxing factor which activates guanylate cyclase nor the factor that induces endothelium-derived hyperpolarization. Inasmuch as relatively low concentrations of the ion induce relaxation of small arteries of skeletal muscle, they could contribute to exercise hyperemia. .A Feletou M; Harker CT; Komori K; Shepherd JT; Vanhoutte PM. .I 201949 .U 90011828 .S J Pharmacol Exp Ther 9001; 251(1):9-15 .M Biological Transport/DE; Female; Human; Imidazoles/PD; In Vitro; Kinetics; Microvilli/*DE/ME; NBD Chloride/PD; Placenta/DE/ME; Pregnancy; Serotonin/*ME; Sodium/PH; Sulfhydryl Reagents/PD; Support, U.S. Gov't, P.H.S.; Tetranitromethane/PD; Tyrosine/*ME. .T Inactivation of the human placental serotonin transporter by tyrosyl group-specific reagents. .P JOURNAL ARTICLE. .W Treatment of human placental brush-border membrane vesicles with tyrosyl group-specific reagents, N-acetylimidazole, 7-chloro-4-nitrobenzo-2-oxa-1,3,-diazole and tetranitromethane, inhibited NaCl gradient-driven serotonin uptake in these vesicles without affecting vesicle integrity. The concentrations of these reagents causing 50% inhibition of serotonin uptake were 3.75 mM, 10 microM and 5 microM, respectively. The inhibition of N-acetylimidazole was reversible with hydroxylamine and the inhibition by 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole was reversible with 2-mercaptoethanol. Kinetic analysis of serotonin uptake in control and in N-acetylimidazole-treated membrane vesicles revealed that the treatment decreased the maximal velocity of the transport system with virtually no effect on the affinity of the transporter for serotonin. Similarly, the treatment did not change the affinity of the transporter for Na+. Even though serotonin uptake was reduced in treated vesicles compared with control vesicles at all concentrations of Na+, in both cases the dependence of the uptake rate on Na+ concentration was hyperbolic, indicating the involvement of one Na+ per transport of one serotonin molecule. The serotonin transporter could be protected from the N-acetylimidazole-induced inhibition by Na+. It is concluded that tyrosyl residues are essential for optimal transport function of the human placental serotonin transporter and that these critical tyrosyl residues are located at or near the Na+-binding site. .A Ganapathy V; Kulanthaivel P; Tiruppathi C; Mahesh VB; Leibach FH. .I 201950 .U 90011829 .S J Pharmacol Exp Ther 9001; 251(1):90-7 .M Animal; Carbachol/*PD; Clone Cells; Fibroblasts/DE; Hydrolysis; Inositol Phosphates/*ME; Mice; Parasympatholytics/DU; Quinuclidinyl Benzilate/AA; Radioligand Assay; Receptors, Muscarinic/DE/*PH; Support, U.S. Gov't, P.H.S.; Transfection. .T The relationship between agonist states of the M1 muscarinic receptor and the hydrolysis of inositol lipids in transfected murine fibroblast cells (B82) expressing different receptor densities. .P JOURNAL ARTICLE. .W We studied the relationship between the M1 muscarinic receptor density and the receptor-mediated hydrolysis of inositol lipids in cloned murine fibroblast B82 cells which were transfected with the m1 muscarinic receptor gene. Of the seven clones examined, the M1 muscarinic receptor densities in these cells characterized by (-)[3H]methyl-3-quinuclidinyl benzilate ([-)-[3H]MQNB binding ranged from 12 fmol/10(6) cells in LK3-1 cells to 260 fmol/10(6) cells in the LK3-8 cells. Carbachol/(-)[3H]MQNB competition curves for the LK3-1 cells (with low receptor density) had a Hill coefficient close to unity. The competition curves for carbachol in the clones with higher receptor densities had Hill coefficients less than 1 and were best fitted by a computerized nonlinear least-squares regression program for the two-site model. The percentage of the M1 muscarinic receptors which had high affinity for carbachol decreased as the receptor density increased, suggesting that the presence of endogenous factors in these cells may be important for the agonist affinity state of the receptor. Concentration-response curves for carbachol-stimulated [3H]inositol monophosphate [( 3H]IP1) accumulation were also obtained. A significant correlation was observed between the density of M1 muscarinic receptor with high affinity for carbachol and the maximum [3H]IP1 accumulation in these cells. There is no significant difference among the EC50 values and the dissociation constant of high-affinity state values of the carbachol/(-)[3H] MQNB competition curves. These results suggest that the high-affinity state for carbachol may be the functional state of the M1 muscarinic receptors in these transfected B82 cells.(ABSTRACT TRUNCATED AT 250 WORDS) .A Mei L; Lai J; Yamamura HI; Roeske WR. .I 201951 .U 90012034 .S J Reprod Med 9001; 34(10):786-9 .M Biopsy/*MT/PX/ST; Comparative Study; Consumer Satisfaction; Dilatation and Curettage/*MT; Endometrium/*; Evaluation Studies; Female; Human; Infertility, Female/DI/*PA; Support, Non-U.S. Gov't; Vacuum Curettage/*MT/PX/ST. .T Evaluation of the Pipelle curette for endometrial biopsy. .P JOURNAL ARTICLE. .W The Pipelle endometrial suction curette was evaluated, and its application and effectiveness were compared to those of the Novak curette for endometrial sampling during the midluteal phase. Fifty women underwent an endometrial biopsy with the Pipelle and Novak curettes. Ninety percent of the women preferred the biopsy with the Pipelle. Histologically, tissue obtained with the Pipelle was satisfactory and similar to that with the Novak. The Pipelle curette appears to be an excellent device for midluteal endometrial biopsy during an infertility evaluation. .A Henig I; Chan P; Tredway DR; Maw GM; Gullett AJ; Cheatwood M. .I 201952 .U 90012035 .S J Reprod Med 9001; 34(10):790-6 .M Adult; Cohort Studies; Female; Human; Incidence; North Carolina; Physicians, Women/*; Pregnancy; Pregnancy Complications/*EP/ET; Risk Factors; Women/*; Women, Working/*. .T Pregnancies among physicians. A historical cohort study. .P JOURNAL ARTICLE. .W Sixty-seven pregnancies in practicing physicians were compared with 201 pregnancies in nonphysicians in a historical cohort study. All subjects were cared for and delivered by the same obstetricians. Physician and nonphysician pregnancies of similar socioeconomic status were matched for age, race and parity. After statistically controlling for alcohol and tobacco use and adequacy of prenatal care, physicians had a 1.86 (1.00, 3.46) relative risk of an adverse pregnancy outcome. Physicians were at a 4.0 (1.58, 10.1) and 2.33 (0.93, 5.8) times higher risk for preterm labor and delivery than were nonphysicians. Pregnancies in physicians were found to be similar to those in nonphysicians in the use of obstetric technology except for an increased number of ultrasound examinations among physicians. These results suggest that physicians are at increased risk for an adverse pregnancy outcome and should be considered and treated as a high-risk obstetric group. .A Miller NH; Katz VL; Cefalo RC. .I 201953 .U 90012039 .S J Reprod Med 9001; 34(10):811-4 .M Adolescence; Adult; Cardiotocography/*IS/MT/ST; Comparative Study; Evaluation Studies; Female; Human; Labor/*; Maintenance/MT/ST; Pregnancy; Prospective Studies; Support, Non-U.S. Gov't; Uterine Contraction. .T Monitoring intrauterine pressure during active labor. A prospective comparison of two methods. .P JOURNAL ARTICLE. .W Conventional recording of intrapartum uterine activity uses fluid-filled internal catheter systems requiring periodic maintenance. An intrauterine pressure catheter system, the INTRAN, uses an electronic pressure sensor and theoretically could obtain satisfactory uterine recordings with less maintenance. Simultaneous recordings with the INTRAN and standard fluid-filled systems were made in 40 third-trimester patients using comparably calibrated electronic monitoring systems. Comparisons of the recordings from each patient showed similar mean baseline uterine tone, contraction interval and duration. Mean peak uterine pressures were significantly higher with the INTRAN system (63 vs. 56 mm Hg). Coefficients of correlation for contraction interval, duration, peak intrauterine pressure and resting tone were .99, .87, .84 and .34, respectively. Both systems detected abnormal uterine activity equally well. Major technical failures were equally frequent with both systems; however, the fluid-filled catheters required more frequent readjustment. .A Devoe LD; Gardner P; Dear C; Searle N. .I 201954 .U 90012040 .S J Reprod Med 9001; 34(10):815-7 .M Cervix Neoplasms/DI/*PC; Clinical Protocols/ST; Colposcopy; Diagnostic Tests, Routine/*; Evaluation Studies; False Negative Reactions; Female; Human; Mass Screening/*ST; Vaginal Smears/*ST. .T Value of repeat cytology at the time of colposcopy for the evaluation of cervical intraepithelial neoplasia on Papanicolaou smears. .P JOURNAL ARTICLE. .W The significance of repeat cervical cytology was evaluated in patients referred for colposcopy because of previous cervical intraepithelial neoplasia (CIN) 1 on cytologic smears. Between Jan 1, 1984, and Dec 31, 1986, 273 such patients were seen. The results of the repeat smears obtained prior to colposcopy were compared with those of colposcopically directed biopsies and of follow-up. The repeat smear was negative in 99 patients; it disclosed squamous atypia in 84, CIN 1 in 64 and CIN 2 or 3 in 26. Thirty-two patients whose repeat smear was negative had biopsy-documented CIN 1-3. Of the 84 patients with squamous atypia, 37 (44%) had biopsy-documented CIN 1-3. Thus, second smears in this group failed to disclose precancerous lesions in at least 69 patients. Of the 90 patients whose repeat smear were interpreted as showing CIN, 64, or 71%, had biopsy-documented CIN 1-3. Patients with a repeat smear showing CIN 1 or greater and normal colposcopy or a negative cervical biopsy must be followed closely: 33% of our study group (6 of 18) were found to have CIN later. .A Wheelock JB; Kaminski PF. .I 201955 .U 90012041 .S J Reprod Med 9001; 34(10):819-23 .M Animal; Dose-Response Relationship, Drug; Female; Labor, Induced/MT; Oxytocin/AD/PD; Pregnancy; Pregnancy, Animal/*DE; Prostaglandins E/AD/PD; Prostaglandins F/AD/PD; Relaxin/AD/*PD; Support, Non-U.S. Gov't; Swine/*PH; Uterine Contraction/*DE. .T Effect of porcine relaxin on spontaneous, oxytocin-driven and prostaglandin-driven pig myometrial activity in vitro. .P JOURNAL ARTICLE. .W The effect of porcine relaxin on myometrial activity was studied in 18 nonpregnant and 54 pregnant pigs. Relaxin inhibited spontaneous contractility in all luteal phase and pregnant pigs. However, similar doses of relaxin had no effect on oxytocin-, prostaglandin E2- or prostaglandin F2 alpha-induced contractions. Only when the doses were increased fivefold to sixfold, to nonphysiologic levels, did relaxin inhibit the action of these oxytocic agents. The effect of relaxin was the same throughout pregnancy. This finding helps explain the two paradoxical roles of relaxin: it inhibits spontaneous myometrial contractility during pregnancy and thus preterm labor but is able to facilitate labor at term through its cervical ripening action without inhibiting the oxytocin- and prostaglandin-driven contractions of parturition. .A Pupula M; MacLennan AH. .I 201956 .U 90012043 .S J Reprod Med 9001; 34(10):827-30 .M Adolescence; Child; Diagnosis, Differential; Endometriosis/*CO/EP/PA; Evaluation Studies; Female; Human; Incidence; Neoplasm Staging; Pain/*DI/ET; Pelvis/*; Peritoneoscopy/*ST. .T Laparoscopy in the diagnosis of chronic pelvic pain in adolescent women. .P JOURNAL ARTICLE. .W Chronic pelvic pain (CPP) in adolescent women is a frequent complaint. We assessed the value of laparoscopy in the differential diagnosis of CPP in 47 adolescents 11-19 years old after six months or more of cyclic or acyclic pelvic pain. No pelvic abnormalities were detected in 19 patients (40.4%), endometriosis was detected in 18 (38.3%) (frequently with nonpigmented or "nonclassic" lesions), partially obstructive genital tract malformations were found in 4 (8.4%), and other types of pathology were discovered in 6 (12.8%). Nearly 60% of the patients had a treatable pelvic disease. Laparoscopy is an invaluable tool in the diagnosis of CPP in adolescents and should be performed before starting a psychiatric evaluation or prescribing long-term medical treatment. .A Vercellini P; Fedele L; Arcaini L; Bianchi S; Rognoni MT; Candiani GB. .I 201957 .U 90012044 .S J Reprod Med 9001; 34(10):831-3 .M Breech Presentation/*; Cesarean Section/PX/*UT; Female; Human; Infant Mortality; Patient Participation; Pregnancy; Pregnancy Outcome; Trial of Labor/*. .T Vaginal birth after cesarean delivery. Trial of labor in women with breech presentation. .P JOURNAL ARTICLE. .W Vaginal birth after cesarean delivery in a woman with breech presentation is a controversial issue. In this prospective study, 137 patients had a breech presentation. Of them, 27 (19.7%) met the protocol criteria for attempted vaginal delivery and desired a trial of labor. Thirteen (48%) achieved vaginal delivery, with no increase in fetal or maternal morbidity. Our data suggest that in selected patients, a trial of labor after a cesarean delivery with a breech presentation is a reasonable consideration. .A Sarno APJr; Phelan JP; Ahn MO; Strong TH Jr. .I 201958 .U 90012045 .S J Reprod Med 9001; 34(10):834-8 .M Adult; Bladder Diseases/CO/DT/*PP; Female; Human; Middle Age; Parasympatholytics/TU; Phenylpropanolamine/TU; Prospective Studies; Urethral Diseases/CO/DT/*PP; Urodynamics/*. .T Detrusor instability. Is the bladder the cause or the effect? .P JOURNAL ARTICLE. .W Seventy-two patients had a clinical and urodynamic diagnosis of detrusor instability. All were given four weeks of anticholinergics (oxybutinin, 5 mg three times a day) and had their evaluation repeated. Forty-one patients (57%) responded favorably to the anticholinergics, and 31 (43%) did not. The 31 discontinued the anticholinergics and were placed on sympathomimetics (phenylpropanlamine, 25 mg two times a day) for another four weeks before repeating their evaluation. Based on urethrocystometry, two groups were identified: group I (n = 44) had bladder contraction that preceded any urethral pressure change, and group II (n = 28) had urethral relaxation that preceded bladder contraction. Most women in group I (38 or the 44 [86%]) responded favorably to anticholinergics. Most women in group II failed to respond to anticholinergics, while more than two-thirds of them (19 of 28 [68%]) responded favorably to sympathomimetics (P less than .001). Our results suggest that bladder contraction that precedes any urethral pressure change represents detrusor pathology as opposed to bladder contraction that follows urethral relaxation: it probably represents urethral pathology. .A Bergman A; Koonings PP; Ballard CA. .I 201959 .U 90012046 .S J Reprod Med 9001; 34(10):839-41 .M Abortion, Therapeutic/*; Adult; Female; Fetal Membranes, Premature Rupture/*CO/DI; Human; Oxytocin/TU; Pregnancy; Pregnancy, Ectopic/*CO/DI; Prostaglandins E/TU. .T A rare gynecologic contraindication to the use of prostaglandins and oxytocin to induce abortion. A case report. .P JOURNAL ARTICLE. .W Premature rupture of the membranes was diagnosed in a 27-year-old nullipara at 24 weeks' gestation. Medical induction of abortion (because of sepsis) was attempted and failed. The products of conception were removed surgically per vagina; that procedure was followed by an intractable hemorrhage. Subtotal hysterectomy and repair of the left common iliac artery and vein were performed to stop the bleeding. In retrospect the case was diagnosed as a left ligamentary ectopic pregnancy with uterine rupture and erosion of the left common iliac vessels. .A Markos AR. .I 201960 .U 90012047 .S J Reprod Med 9001; 34(10):842-4 .M Adult; Case Report; Female; Fluorescein Angiography; Human; Pre-Eclampsia/*CO; Pregnancy; Puerperium/*; Retinal Detachment/DI/*ET/PP. .T Postpartum retinal detachment. A case report. .P JOURNAL ARTICLE. .W A postpartum progression of preeclampsia ultimately resulted in bilateral serous retinal detachment. .A Chatwani A; Oyer R; Wong S. .I 201961 .U 90012048 .S J Reprod Med 9001; 34(10):845-9 .M Adenocarcinoma/*EP/ET/PA; Adolescence; Adult; Age Factors; Case Report; Female; Human; Incidence; Neoplasm Staging; Risk Factors; Uterine Neoplasms/*EP/ET/PA. .T Endometrial carcinoma in young women. A report of four cases. .P JOURNAL ARTICLE. .W Endometrial carcinoma in young women is a rare but well-documented clinicopathologic entity. Four cases revealed some unusual clinical and pathologic features. Patient 1 was the first recorded case of a young woman (aged 24) on maintenance peritoneal dialysis for chronic renal failure who developed endometrial carcinoma with nonvirilizing oligoovulatory polycystic ovarian enlargement. Following subtotal proctocolectomy for familial polyposis coli complicated by a colonic and rectal carcinoma, patient 2 developed, at age 24, a grade 3 endometrial carcinoma in the absence of any risk factors; she was still alive three years postoperatively despite the subsequent development of a grade 3 astrocytoma in the left temporal region. Patient 3 presented at age 32 after ten years of amenorrhea with the clinical features of the Stein-Leventhal syndrome and abnormal uterine bleeding related to a grade 1 endometrial carcinoma; she also had focal dysplasia and adenocarcinoma in situ of the endocervix. Patient 4, who had no risk factors, developed a grade 2 endometrial carcinoma at age 34 despite constant use of combined oral contraceptives for one year and intermittent exposure to them for the previous ten years. Endometrial carcinoma is a rare but important cause of abnormal uterine bleeding in young women; the prognosis can be improved only by prompt diagnosis and appropriate therapy. .A Honore LH; Davey SJ. .I 201962 .U 90012051 .S J Reprod Med 9001; 34(10):857-60 .M Case Report; Cerebral Angiography; Cesarean Section; Craniotomy; Diagnosis, Differential; Female; Human; Middle Age; Pre-Eclampsia/*CO; Pregnancy; Subarachnoid Hemorrhage/*ET/RA/SU; Tomography, X-Ray Computed. .T Maternal intracranial hemorrhage complicating severe superimposed preeclampsia. A case report. .P JOURNAL ARTICLE. .W Subarachnoid hemorrhage as a result of superimposed preeclamptic toxemia is a well-known complication but fortunately not a common one. The maternal and fetal mortality rates are high. In one such patient the outcome for both mother and infant was excellent. .A Lazebnik N; Pazmino R; Dierker LR; Takaoka Y; Warf BC. .I 201963 .U 90012052 .S J Reprod Med 9001; 34(8 Suppl):553-609 .M Female; Human; Support, Non-U.S. Gov't; Vaginal Diseases/*TH; Vulvar Diseases/*TH; Vulvovaginitis/*TH. .T Advances in the management of vulvovaginal disease: a symposium. .P JOURNAL ARTICLE. .I 201964 .U 90012060 .S J Reprod Med 9001; 34(8 Suppl):602-4 .M Chlamydia Infections/DI; Female; Gardnerella vaginalis; Haemophilus Infections/DI; Human; Pregnancy; Pregnancy Complications, Infectious/*DI; Pregnancy Trimester, First; Streptococcus/IP; Vaginitis/*DI. .T Vaginitis and pregnancy. .P JOURNAL ARTICLE. .W Vaginitis in pregnant women can affect the outcome of the pregnancy through preterm labor, premature rupture of the membranes, chorioamnionitis, neonatal infection and postpartum endometritis. Women can be screened for group B streptococci, and infection in the newborn can be prevented by the institution of antibiotic therapy in labor. Screening pregnant women for bacterial vaginitis can reduce the risk of premature rupture of the membranes, premature labor and neonatal infection. .A Faro S. .I 201965 .U 90012240 .S J Natl Cancer Inst 9001; 81(20):1524-5 .M Human; Lung Neoplasms/ET; Smoking/*PC. .T Battle against tobacco [editorial] .P EDITORIAL. .A Stjernsward J. .I 201966 .U 90012241 .S J Natl Cancer Inst 9001; 81(20):1526-8 .M Animal; Animal Welfare/*; Animals, Laboratory/*; United States. .T Animals in research: researchers must tell their story [news] .P NEWS. .A Kumar S. .I 201967 .U 90012242 .S J Natl Cancer Inst 9001; 81(20):1530-1 .M Fatty Acids, Omega-3/*TU; Human; Neoplasms/*PC; Risk Factors. .T Seafood fatty acids may lower cancer risk [news] .P NEWS. .A Corliss J. .I 201968 .U 90012243 .S J Natl Cancer Inst 9001; 81(20):1531-3 .M Female; Health Education; Human; Latin America; Male; Smoking/*PC. .T U.S. groups to help control Latin American smoking epidemic [news] .P NEWS. .A Neild J. .I 201969 .U 90012244 .S J Natl Cancer Inst 9001; 81(20):1533-5 .M Gene Therapy; Human; Transfection/*. .T Update on gene transfer trial [news] .P NEWS. .A Antoine FS. .I 201970 .U 90012245 .S J Natl Cancer Inst 9001; 81(20):1535-7 .M Female; Health Promotion; Human; Mammography/*. .T The Women's Leadership Summit on Mammography held at the U.S. Capitol [news] .P NEWS. .A Wittenberg CK. .I 201971 .U 90012247 .S J Natl Cancer Inst 9001; 81(20):1545-51 .M Animal; Culture Media; Dogs; Female; Fetal Blood/PH; Mammary Neoplasms/*PA; Mice; Mice, Inbred C3H; Support, Non-U.S. Gov't; Tumor Cells, Cultured. .T Isolation of autonomously growing dog mammary tumor cell lines cultured in medium supplemented with serum treated to inactivate growth factors. .P JOURNAL ARTICLE. .W Conventional methods for isolation of cell lines from carcinomas suffer inherently from a lack of advantage for proliferation of transformed cells as opposed to contaminating fibroblasts and normal epithelial cells. To isolate cell lines from metastases of estrogen receptor-negative mammary carcinomas in dogs, we applied a novel method using medium supplemented with serum treated to inactivate growth factors. Under these conditions, autonomously growing tumor cells are selectively allowed to proliferate. In this way, four autonomously growing tumor cell lines were obtained from metastases of two dogs. Tumors formed from cells implanted in C3H nude mice closely resembled the original dog tumors, indicating that the main result of this selective procedure was suppression of normal cell proliferation. Serum treated to inactivate growth factors seems to be an important medium supplement for isolation of autonomously growing tumor cell lines, which may be valuable tools for future studies on regulation of cell proliferation in advanced hormone-independent mammary tumors. .A van der Burg B; van Selm-Miltenburg AJ; van Maurik P; Rutteman GR; Misdorp W; de Laat SW; van Zoelen EJ. .I 201972 .U 90012248 .S J Natl Cancer Inst 9001; 81(20):1552-60 .M Cisplatin/*PK/TO; Diethyldithiocarbamate/PD; Human; Kidney/DE; Magnesium/BL; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Thiosulfates/*PD/PK. .T Effect of sodium thiosulfate on the pharmacokinetics and toxicity of cisplatin. .P JOURNAL ARTICLE. .W Concurrent administration of sodium thiosulfate (STS) can protect against the nephrotoxic effects of even very-high-dose cisplatin (CDDP) (i.e., 270 mg/m2 given intraperitoneally). The effect of STS on the pharmacology and toxicity of CDDP was investigated in patients receiving at each treatment 90 mg of CDDP/m2 intraperitoneally, with STS given concurrently on alternate cycles by the intravenous route. The patients received a total of 38 courses of therapy, 21 without STS and 17 with STS. STS reduced the total exposure to diethyldithiocarbamate-reactive CDDP for the peritoneal cavity and plasma by 36% and 25%, respectively. When given alone, CDDP caused a statistically significant acute reduction in creatinine clearance levels; this reduction was less evident when STS was given. We conclude that, whereas STS does reduce systemic exposure, the magnitude of this effect was not sufficient to account for the ability of STS to protect against high-dose CDDP. .A Goel R; Cleary SM; Horton C; Kirmani S; Abramson I; Kelly C; Howell SB. .I 201973 .U 90012249 .S J Natl Cancer Inst 9001; 81(20):1560-7 .M Case-Control Studies; Environmental Exposure; Female; Human; Hypersensitivity/ET; Male; Middle Age; Mycosis Fungoides/*ET/IM; Neoplasms/ET; Occupations; Risk Factors; Skin Neoplasms/*ET/IM; Socioeconomic Factors; Support, U.S. Gov't, P.H.S.. .T Mycosis fungoides in relation to environmental exposures and immune response: a case-control study. .P JOURNAL ARTICLE. .W Mycosis fungoides is a cutaneous T-cell lymphoma of unknown etiology, thought to be a rare sequela of chronic antigenic stimulation that may occur, for example, with exposure to contact allergens. To explore this possibility, we interviewed 174 patients with mycosis fungoides and 294 randomly selected control subjects in the San Francisco, Los Angeles, and Seattle areas concerning their lifetime histories of employment, chemical exposures, allergy, atopy, and certain medical conditions. Patients reported higher prevalence of cancers other than the non-Hodgkin's lymphomas and skin cancers (relative risk = 3.3, P less than .001) and were more likely than controls to burn when exposed to the sun (for nonblacks, relative risk = 1.7, P = .01). The latter difference may reflect a manifestation rather than a precursor of the disease. We found no consistent or biologically plausible differences between patients and controls with respect to types of jobs held, or to occupational or vocational exposures to chemicals. These findings do not support the hypothesis that persistent antigenic stimulation by contact allergens is etiologically important in the pathogenesis of mycosis fungoides. .A Whittemore AS; Holly EA; Lee IM; Abel EA; Adams RM; Nickoloff BJ; Bley L; Peters JM; Gibney C. .I 201974 .U 90012250 .S J Natl Cancer Inst 9001; 81(20):1568-71 .M Adult; Age Factors; Aged; Cohort Studies; Female; Human; Lung Neoplasms/EP/*MO; Male; Middle Age; Smoking/EP; United States/EP. .T Declining lung cancer rates among young men and women in the United States: a cohort analysis [see comments] .P JOURNAL ARTICLE. .W Although overall age-adjusted rates of mortality from lung cancer in the United States continue to rise, rates at ages below 45 years have begun to decline. In this report we show that the decrease is greatest among white men, with a 29% drop between the mid-1970s and mid-1980s, but a decrease also occurred among black men and white and black women. Cohort analyses revealed that the rates of lung cancer peaked among men born around 1925-1930 and among women born around 1935-1940, and have declined thereafter. If these trends continue, overall lung cancer mortality rates will start to decline in the 1990s among men and after the year 2000 among women. .A Devesa SS; Blot WJ; Fraumeni JF Jr. .I 201975 .U 90012252 .S J Natl Cancer Inst 9001; 81(20):1575-80 .M Antigens, Tumor-Associated, Carbohydrate/*AN; Bile/*AN; Carcinoembryonic Antigen/*AN; Cell Cycle; DNA, Neoplasm/*AN; Flow Cytometry/*; Gallbladder Neoplasms/*AN; Human; Multivariate Analysis; Neoplasm Staging; Support, U.S. Gov't, P.H.S.. .T Pathophysiology of tumor progression in human gallbladder: flow cytometry, CEA, and CA 19-9 levels in bile and serum in different stages of gallbladder disease. .P JOURNAL ARTICLE. .W Gallbladder epithelium is unique among the gastrointestinal cell types because proteins and protein levels in the fluid bathing the luminal side of the cells (bile) are different from and can be compared with those in the fluid bathing the basal side (serum). To help identify cellular changes that occur during the development of gallbladder cancer, we obtained gallbladder tissue, serum, and bile specimens from 20 patients with invasive adenocarcinoma of the gallbladder, three with high-grade dysplasia (carcinoma in situ), six with low-grade dysplasia, 12 with hyperplasia, and 10 with acute or chronic cholecystitis. We obtained serum samples from 40 patients with invasive adenocarcinoma and bile samples from 29 of these patients; serum samples from three with high-grade dysplasia and bile specimens from two of these; serum and bile samples from five with low-grade dysplasia; serum or bile samples from 126 with metaplasia, hyperplasia, or cholecystitis, including serum samples from 121 and bile samples from 110; and serum and bile samples from eight with normal biliary tracts. The study was conducted in Mexico City, Mexico, and La Paz, Bolivia. We performed flow cytometric DNA analysis on gallbladder tissue specimens and measured levels of carcinoembryonic antigen (CEA) and CA 19-9 antigen in the serum and bile specimens. Analysis of the cell cycle compartments by flow cytometry revealed marked variations of the proliferation index for the different disease states (P less than .0001). The proliferation index increased with progression from cholecystitis to invasive adenocarcinoma. Of the bile and serum measurements, only serum CA 19-9 values were correlated with flow cytometry measurements (r = -.49, P = .005). Overall, the serum and bile measurements were in agreement (P less than .01). However, with the exception of the correlations among serum measurements for the patients with invasive adenocarcinoma, most of the correlations could be explained by differences in the disease state. In particular, the progression from normal tissue to invasive adenocarcinoma involved no change in bile CA 19-9 level and only a slight change in bile CEA level but much larger changes in serum CEA and CA 19-9 levels. It appears that the progression from normal tissue to invasive adenocarcinoma results in increased production of these antigens and often in loss of cell polarity as well, i.e., inability to prevent leakage of the antigens into the serum. .A Strom BL; Iliopoulos D; Atkinson B; Herlyn M; West SL; Maislin G; Saul S; Varello MA; Rodriguez-Martinez HA; Rios-Dalenz J; et al. .I 201976 .U 90012254 .S J Natl Cancer Inst 9001; 81(20):1586-7 .M Animal; Cyanates/*TO; Female; Lung/*DE; Male; Mice; Mice, Inbred Strains; Neoplasms, Experimental/*CI; Rats; Rats, Inbred F344. .T Carcinogenicity and pulmonary pathology associated with a single 2-hour inhalation exposure of laboratory rodents to methyl isocyanate [letter] .P LETTER. .A Bucher JR; Uraih LC; Hildebrandt PK; Sauer RM; Seely JC. .I 201977 .U 90012255 .S J Natl Cancer Inst 9001; 81(20):1587-8 .M Human; Male; Patient Compliance/*; Testicular Neoplasms/PX/*TH. .T Refusal of cancer treatment in testicular cancer patients [letter] .P LETTER. .A Moul JW; Paulson DF; Walther PJ. .I 201978 .U 90012256 .S J Natl Cancer Inst 9001; 81(20):1588-90 .M Animal; Drug Resistance; Membrane Glycoproteins/ME; Mice; Tumor Cells, Cultured/DE; Verapamil/*PD. .T Collateral resistance to verapamil in multidrug-resistant mouse tumor cells [letter] .P LETTER. .A Reeve JG; Wright KA; Rabbitts PH; Twentyman PR; Koch G. .I 201979 .U 90012257 .S J Natl Cancer Inst 9001; 81(20):1590-1 .M Book Reviews; Human; Interferons/*TU; Neoplasms/*TH. .T Cancer biotherapy [letter] .P LETTER. .A Oldham RK. .I 201980 .U 90012258 .S J Natl Cancer Inst 9001; 81(21):1600-1 .M Animal; Antibodies, Monoclonal/*TU; Human; Neoplasms/*TH; Receptors, Epidermal Growth Factor-Urogastrone/*IM. .T Growth factor receptor monoclonal antibodies and cancer immunotherapy [editorial] .P EDITORIAL. .A Sato GH; Sato JD. .I 201981 .U 90012259 .S J Natl Cancer Inst 9001; 81(21):1602-4 .M Brain Neoplasms/*TH; Combined Modality Therapy; Human. .T New approaches tried in treating brain tumors [news] .P NEWS. .A McIntosh H. .I 201982 .U 90012260 .S J Natl Cancer Inst 9001; 81(21):1605-7 .M Antineoplastic Agents, Combined/*TU; Colonic Neoplasms/*DT; Fluorouracil/AD; Human; Levamisole/AD. .T Adjuvant therapy benefits Dukes' C colon cancer patients [news] .P NEWS. .A Smigel K. .I 201983 .U 90012262 .S J Natl Cancer Inst 9001; 81(21):1609-10 .M Breast Neoplasms/*PC; Female; Human; Legislation, Medical/*; United States. .T House legislators sponsor new breast cancer bills [news] .P NEWS. .A Vanchieri C. .I 201984 .U 90012263 .S J Natl Cancer Inst 9001; 81(21):1616-25 .M Animal; Antibodies, Monoclonal/*DU; Female; Human; Indium Radioisotopes/*DU; Infant; Mammary Neoplasms, Experimental/RI; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Neoplasms, Experimental/*RI; Receptors, Epidermal Growth Factor-Urogastrone/AN/*IM; Support, U.S. Gov't, P.H.S.; Transplantation, Heterologous; Vulvar Neoplasms/RI. .T Imaging of human tumor xenografts with an indium-111-labeled anti-epidermal growth factor receptor monoclonal antibody. .P JOURNAL ARTICLE. .W The mouse monoclonal antibody (mAb) 225 IgG1 against the epidermal growth factor (EGF) receptor has been investigated for its capacity to localize in human tumor xenografts. The EGF receptor is the product of the c-erb-B proto-oncogene (also known as EGFR). Elevated expression of EGF receptors has been demonstrated in many human tumors and tumor cell lines. We studied A431 human vulvar squamous cell carcinoma cells, with 2 X 10(6) receptors per cell; MDA-MB-468 (MDA 468) human breast adenocarcinoma cells, with 3 X 10(5) receptors per cell; and MCF-7 human breast adenocarcinoma cells, with 5 X 10(3) receptors per cell. The 111In-labeled pentetic acid (DTPA), derivative of mAb 225 (111In-DTPA-225) was injected intraperitoneally into nude mice bearing subcutaneous tumor xenografts. We measured uptake by quantifying radioactivity in tumor and normal tissues and by obtaining gamma camera images. Uptake in A431 xenografts was 28% +/- 2.4% of the injected dose per gram of tumor on day 3 and 12.4% +/- 3.0% on day 7. Distribution ratios comparing uptake in the tumor with that in normal tissues were consistently greater than 4. In contrast, there was far less uptake of the control mAb KS1/4S-1 labeled with 111In. This conjugate, 111In-DTPA-KS1/4S-1, has an IgG1 isotype but does not bind to human or murine cells. Imaging of the tumor with mAb 225 was excellent, especially on days 3-7. MDA 468 xenografts exhibited reduced localization of mAb 225 in the tumor. For MCF-7 xenografts, the tumor uptake of mAb 225 after 7 days was only 0.70% +/- 0.10% of the injected dose per gram of tumor, which was comparable to the uptake of the KS1/4S-1 control mAb. The ratio of the concentration of radioactivity in the tumor to that in normal tissue (distribution ratio) showed poor selectivity of uptake, and imaging was not obtained. These observations suggest that labeled mAb can target the product of a proto-oncogene, the EGF receptor, when it is expressed at high levels in human tumor xenografts. .A Goldenberg A; Masui H; Divgi C; Kamrath H; Pentlow K; Mendelsohn J. .I 201985 .U 90012264 .S J Natl Cancer Inst 9001; 81(21):1625-31 .M Adult; Age Factors; Breast Neoplasms/*ET; Female; Human; Lymphatic Metastasis; Menopause; Middle Age; Prospective Studies; Risk Factors; Smoking/*AE; Support, U.S. Gov't, P.H.S.. .T Prospective study of smoking and the risk of breast cancer. .P JOURNAL ARTICLE. .W In 1976, 117,557 women in the United States aged 30-55 years and without a history of cancer provided detailed information on current smoking habits. By 1986, 1,788 cases of breast cancer had been documented during 1,133,682 person-years. There was no association between current smoking and risk of breast cancer (multivariate-adjusted relative risk for smokers of greater than or equal to 25 cigarettes/day compared to nonsmokers: 1.02, 95% confidence interval, 0.96-1.22). Past smoking also was unrelated to breast cancer risk (relative risk, 1.08; 95% confidence interval, 0.96-1.20). The results did not differ by menopausal status. Tumor size and the presence of nodal metastases were unrelated to smoking. Smoking was weakly associated with estrogen receptor-positive tumors (relative risk for smokers of greater than or equal to 25 cigarettes/day compared with never smokers, 1.38; 95% confidence interval, 1.04-1.84), but there was no dose-response relationship across categories of current smoking. These results suggest that smoking and breast cancer are not materially related. .A London SJ; Colditz GA; Stampfer MJ; Willett WC; Rosner BA; Speizer FE. .I 201986 .U 90012266 .S J Natl Cancer Inst 9001; 81(21):1640-7 .M Adult; Age Factors; Aged; Female; Human; Life Expectancy; Male; Middle Age; Multivariate Analysis; Neoplasms/DI/*MO; Sex Factors; Support, Non-U.S. Gov't; Survival Analysis; Survival Rate; Sweden/EP; Time Factors. .T Increasing survival trend after cancer diagnosis in Sweden: 1960-1984 [see comments] .P JOURNAL ARTICLE. .W We analyzed the survival trend after cancer was diagnosed by complete follow-up through 1986 of 591,456 (99.4%) of all those patients in whom a first malignant disease was diagnosed in Sweden from 1960 to 1984. From 1960-1964 to 1980-1984, the 5-year relative survival increased from 34.2% to 47.1% in males and from 48.7% to 56.9% in females. The mean loss of expected life among cancer patients decreased from 9.6 to 7.0 years. During the first 5 years after diagnosis, the cancer-specific hazard rate decreased by 34% in males and 30% in females. Thus several analytical approaches revealed a substantial increase in cancer patient survival since 1960. .A Adami HO; Sparen P; Bergstrom R; Holmberg L; Krusemo UB; Ponten J. .I 201987 .U 90012267 .S J Natl Cancer Inst 9001; 81(21):1649-52 .M Carotene/*PD; Cell Division/DE; Human; Interphase/DE; Neuroblastoma/*PA; Proto-Oncogenes; RNA, Messenger/AN; Tumor Cells, Cultured. .T Inhibitory effects of alpha-carotene on proliferation of the human neuroblastoma cell line GOTO. .P JOURNAL ARTICLE. .W alpha-Carotene inhibited the proliferation of the human neuroblastoma cell line GOTO in a dose- and time-dependent manner. In addition, it was about 10 times more inhibitory than beta-carotene. Northern blot analysis indicated that alpha-carotene caused maximum suppression of the level of the N-myc messenger RNA of GOTO cells. This suppression occurred within 18 hours of alpha-carotene treatment, after which the level of the N-myc messenger RNA gradually recovered to the basal level. Analysis by flow cytometry indicated that when GOTO cells were exposed to alpha-carotene, they were arrested in the G0-G1 phase of their cell cycle. However, as the level of the N-myc messenger RNA was recovering, these cells resumed normal cycling. These results indicate that the reduction in the level of the N-myc messenger RNA caused by alpha-carotene is closely linked with G0-G1 arrest. .A Murakoshi M; Takayasu J; Kimura O; Kohmura E; Nishino H; Iwashima A; Okuzumi J; Sakai T; Sugimoto T; Imanishi J; et al. .I 201988 .U 90012268 .S J Natl Cancer Inst 9001; 81(21):1652-5 .M Albinism/GE; Animal; Chromosome Mapping/*; Genes, Recessive; Genes, Viral; Lymphoma/CI/*GE; Methylnitrosourea; Mice; Mice, Inbred AKR; Mouse Leukemia Viruses/GE; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Thymus Neoplasms/CI/*GE. .T Genetics of N-methyl-N-nitrosourea induction of thymic lymphomas in AKR/J mice: assignment of a susceptibility gene to mouse chromosome 7. .P JOURNAL ARTICLE. .W Treatment of young AKR/J mice with N-methyl-N-nitrosourea (MNU) results in the induction of a high incidence of thymic lymphomas occurring between 4 and 6 months of age. The tumor incidence is higher and the latency period is shorter than that observed in other MNU-treated mouse strains. Analysis of tumor incidence in crosses of AKR/J with C57L/J mice indicates that several genes influence the incidence and latency of MNU-induced thymic lymphomas. One of these genes appears to be tightly linked to the albino locus of chromosome 7. .A Angel JM; Morizot DC; Richie ER. .I 201989 .U 90012269 .S J Natl Cancer Inst 9001; 81(21):1655-60 .M Antigens, Neoplasm/IM; Cytotoxicity, Immunologic; Human; Immunotherapy; Lymphocyte Transformation/*; Lymphocytes/*IM; Neoplasms/IM/*TH; Phenotype; Tumor Cells, Cultured. .T Activation and expansion of tumor-derived activated cells for therapeutic use. .P JOURNAL ARTICLE. .W We obtained tumor specimens from patients with cancer in an effort to activate and expand the tumor-infiltrating lymphocytes for therapeutic use. With the use of finely minced tumor preparations from eight different tumor types, recombinant interleukin-2, and lymphokine-activated killer cell-conditioned medium, lymphocytes were expanded in vitro. After 4 weeks, the tumor cells were virtually absent from the cultures. At this point, the lymphocytes were termed "tumor-derived activated cells" (TDACs). Over 90% of the TDACs from each of the different tumor types were T lymphocytes, and the percentage of cells expressing either CD4 or CD8 varied considerably from population to population. The lymphocytes showed specific cytolytic activity in melanoma and colon and renal cell carcinomas. Continued expansion and long-term growth of the TDACs, as well as maintenance of the cytolytic activity, were achieved by periodic stimulation of the TDACs with irradiated autologous tumor cells. In a clinical study of 28 patients with cancer, we generated a mean number of 1.2 X 10(11) TDACs in an average time in culture of 69 days. These TDACs were subsequently infused into the patients with cancer. TDACs appear to represent an important resource for biotherapy of patients with cancer. .A Maleckar JR; Friddell CS; Sferruzza A; Thurman GB; Lewko WM; West WH; Oldham RK; Yannelli JR. .I 201990 .U 90012270 .S J Natl Cancer Inst 9001; 81(21):1660-3 .M Animal; Epidermal Growth Factor-Urogastrone/*PH; Female; Male; Mammary Neoplasms, Experimental/*ET/PA; Mice; Mice, Inbred C3H; Neoplasm Transplantation; Precancerous Conditions/*ET; Submandibular Gland/*PH. .T Incidence of precancerous foci of mammary glands and growth rate of transplantable mammary cancers in sialoadenectomized mice. .P JOURNAL ARTICLE. .W Sialoadenectomies performed on 8-week-old female SHN and GR mice markedly reduced the numbers of precancerous and cancerous lesions in their mammary glands that had been mildly hypoplastic; the mice were necropsied when they were 30 weeks old. The success rate of the mammary cancer transplantation to isogenic male SHN or C3H mice was lower in the sialoadenectomized animals, and growth of the grafted tumors was delayed after gland removal. Some tumor development resumed in the hosts that received mouse epidermal growth factor after surgery. Therefore, we believe this growth factor may play a role in the multistage process of mouse mammary carcinogenesis. .A Inui T; Tsubura A; Morii S. .I 201991 .U 90012271 .S J Natl Cancer Inst 9001; 81(21):1668 .M Human; Research; Smoking/*AE. .T Smoking: the need for further medical studies [letter] .P LETTER. .A Gourgoulianis KI. .I 201992 .U 90012272 .S J Natl Cancer Inst 9001; 81(21):1668-9 .M Adult; Denmark/EP; Human; Male; Risk Factors; Testicular Neoplasms/EP/*ET; War. .T Decreased testicular cancer risk in men born in wartime [letter] .P LETTER. .A Moller H. .I 201993 .U 90012284 .S J Subst Abuse Treat 9001; 6(3):147-57 .M Alcoholics Anonymous; Depressive Disorder/CO; Environment; Human; Learning; Models, Psychological/*; Morals; Self Medication; Substance Dependence/*ET/TH; Support, U.S. Gov't, P.H.S.. .T Treatment implications of chemical dependency models an integrative approach. .P JOURNAL ARTICLE. .W Five basic models of chemical dependency and their treatment implications are described. The moral model, although disdained by most treatment professionals, actually finds expression in over half the steps of Alcoholics Anonymous. The learning model, albeit the center of the controlled drinking controversy, is also utilized by most abstinence-oriented programs. The disease model, which enjoys current popularity, sometimes ignores the presence of coexisting disorders. The self-medication model, which tends to regard chemical dependency as a symptom, can draw needed attention to coexisting disorders. The social model emphasizes the importance of environmental and interpersonal influences in treatment, although the substance abuser may endorse it as a justification to adopt a victim's role. A sixth model, the dual diagnosis model, is presented as an example of how two of the basic models can be integrated both to expand the treatment focus and to increase treatment leverage. Whereas the five basic models are characterized by a singular, organizing treatment focus, the dual diagnosis model is viewed as an example of a multifocused, integrative model. It is concluded that effective therapy requires (a) flexibility in combining elements of different models in order to individualize treatment plans for substance abusers, and (b) careful assessment of both the therapist's and the substance abuser's beliefs about treatment models in order to insure a treatment match based on a healthy alliance. .A Brower KJ; Blow FC; Beresford TP. .I 201994 .U 90012286 .S J Subst Abuse Treat 9001; 6(3):163-8 .M Adult; Alcoholism/CO; Antisocial Personality Disorder/CO; Borderline Personality Disorder/CO; Crime; Depressive Disorder/CO; Female; Human; Male; Narcotic Dependence/*CO; Personality Disorders/*CO; Prognosis; Support, U.S. Gov't, P.H.S.. .T Personality disorders in opiate addicts show prognostic specificity. .P JOURNAL ARTICLE. .W Early studies examining the relationship of personality disorders to opiate addiction attempted to define an "addictive personality." Later research found that personality disorders in opiate addicts were common but heterogeneous. We examined whether different comorbid personality disorders have prognostic specificity. Rates of depression and alcoholism as well as assessments of specific problems were measured in a 2.5-year follow-up of 150 treated opioid addicts. Using DSM-III criteria, we found that borderline personality disorder predicted more depressive disorders and alcoholism at follow-up; yet greater recovery from these disorders was seen. Borderline patients had more severe psychiatric problems as measured by the Addiction Severity Index. Other ASI outcomes differed by personality disorder; antisocial addicts had more legal problems, and narcissistic addicts had more medical problems. These results suggest that treatment for opiate addicts be tailored to the specific needs of the patients, which can be predicted, in part, by their comorbid personality disorder diagnosis. .A Kosten TA; Kosten TR; Rounsaville BJ. .I 201995 .U 90012287 .S J Subst Abuse Treat 9001; 6(3):169-81 .M Activities of Daily Living; Adult; Aged; Combined Modality Therapy; Counseling; Crisis Intervention; Female; Heroin Dependence/*RH; Human; Male; Methadone/*TU; Middle Age; Patient Education/*; Psychotherapy, Group/*. .T A psychoeducational approach to methadone maintenance treatment. .P JOURNAL ARTICLE. .W Methadone maintenance has become the treatment of choice for heroin addiction because of its beneficial effects on illicit opiate use and criminality. Yet methadone maintenance falls short in a variety of ways; methadone clients continue to use drugs, experience high rates of psychopathology and alcoholism, and fail to become employed and integrated into the community. These problems are endemic in addicts, but also can be attributed to a host of strategic and tactical failures in methadone maintenance treatment itself. Traditional counseling is an inadequate and confused way to provide clients with the living skills, psychotherapy, and limit setting they need. S.T.A.R. is a methadone program in Portland, Oregon, that emphasizes direct training of educational, recreational, and personal skills. Group treatment is employed to create social support for clients while psychotherapy and crisis counseling are available on an as-needed basis. Implementation of the model has caused some difficulties and has led to creative and promising results. .A Stark MJ. .I 201996 .U 90012289 .S J Subst Abuse Treat 9001; 6(3):193-9 .M Awareness; Conflict (Psychology); Family; Fantasy; Human; Infanticide; Parent-Child Relations; Psychological Theory; Psychotherapy; Self Concept; Substance Abuse/*PX/TH; Therapeutic Community. .T Denial of the inner reality: observations on drug abuse and addiction based on psychotherapies after treatment in a therapeutic community in The Netherlands. .P JOURNAL ARTICLE. .W Public opinion and a great deal of political action regarding the use of drugs and the desired approach to it only reflect the surface of the phenomenon. This is alarming, especially in view of the problems that lie behind alcohol and drug abuse and addiction. Alarm is also appropriate in consideration of the consequences of the neglect of personal and relational information for the individual addict as well as for society and culture. A clarification of this is given in this article by an explanation of the problems that lie behind addiction. Information about this has been derived from long-term intensive psychodynamic psychotherapies of addicts and their families of origin. It involves a phenomenological description of the intrapsychic and interpersonal psychopathology behind the addiction phenomenon. An explanatory theory of the origin of addiction is not given, nor are the findings placed into diagnostic categories. .A Vos HP. .I 201997 .U 90012290 .S J Subst Abuse Treat 9001; 6(3):201-4 .M Academic Medical Centers/*; Adolescence; Adult; Aged; Aged, 80 and over; Alcoholism/*TH; Female; Human; Male; Middle Age; New York; Patient Care Team; Psychotherapy; Referral and Consultation. .T New York Hospital--Westchester Division--Cornell University Medical College: a tradition in the treatment of alcoholism. .P JOURNAL ARTICLE. .A Miller NS; Frances RJ. .I 201998 .U 90012291 .S J Subst Abuse Treat 9001; 6(3):205-6 .M Analeptics/*AE; Human; Plant Extracts/*AE; Psychoses, Substance-Induced/*ET. .T Khat, toxic reactions to this substance, its similarities to amphetamine, and the implications of treatment for such patients [letter; comment] .P COMMENT; LETTER. .A Pantelis C; Hindler CG; Taylor JC. .I 201999 .U 90012371 .S J Urol 9001; 142(4):1011-7 .M Acid Phosphatase/AN; Antigens, Neoplasm; Hormones/TU; Human; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Prostate/EN; Prostatectomy; Prostatic Neoplasms/*DI/IM; Radioimmunoassay; Support, Non-U.S. Gov't; Tumor Markers, Biological. .T Clinical use of prostate specific antigen in patients with prostate cancer. .P JOURNAL ARTICLE. .W The clinical use of prostate specific antigen as a screening test for prostate cancer, as a preoperative determinant for staging of prostate cancer and to monitor response to therapy in prostatic cancer patients was evaluated in 168 men with benign prostatic hyperplasia and 231 men with prostate cancer. Only 3% of the men with benign prostatic hyperplasia had prostate specific antigen levels greater than 10 ng. per ml. compared to 44% of the men with proved prostate cancer. Preoperative prostate specific antigen levels increased with higher clinical stages of prostate cancer but there was substantial overlap among stages. Among patients with stage A1 prostate cancer who were followed expectantly none had an elevated prostate specific antigen value or metastatic disease during a followup of 15 to 120 months. After radical prostatectomy serum prostate specific antigen values decreased to undetectable levels (less than 0.6 ng. per ml.) in 89% of the patients with organ-confined disease, in 87% of those with microscopically positive margins only but in only 34% with seminal vesicles or lymph node involvement. Failure of the prostate specific antigen levels to decrease to the undetectable range after radical prostatectomy was associated with a greater likelihood of subsequent tumor recurrence. Only 3 of 18 patients (17%) treated with definitive radiation therapy had post-irradiation prostate specific antigen values of less than 0.6 ng. per ml., while in 39% the prostate specific antigens values remained greater than 4 ng. per ml. and in 4 of 18 (22%) the values were greater than 10 ng. per ml. Of patients with previously untreated stage D2 prostate cancer the mean pre-treatment prostate specific antigen value was 63.7 ng. per ml. compared to a post-hormonal therapy mean value of 31.1 ng. per ml. Of 32 patients treated with hormonal therapy 14 had stable disease, including 13 with prostate specific antigen levels of less than 10 ng. per ml. In contrast, 18 patients had progressive disease, of whom 16 had prostate specific antigen levels of more than 10 ng. per ml. We conclude that the serum prostate specific antigen assay is most useful clinically to monitor the response to therapy of prostate cancer patients. .A Hudson MA; Bahnson RR; Catalona WJ. .I 202000 .U 90012372 .S J Urol 9001; 142(4):1018-20 .M Absorption; Adolescence; Adult; Calcium/*UR; Dietary Fiber/*; Female; Human; Male; Middle Age; Oxalates/UR; Phosphates/UR; Time Factors; Uric Acid/UR; Urinary Calculi/BL/DH/*UR. .T Wheat bran in the selective therapy of absorptive hypercalciuria: a study performed on 18 lithiasic patients. .P JOURNAL ARTICLE. .W The binding properties of raw vegetable fiber towards bivalent cations suggested the prescription of brain as a dietary supplement to limit intestinal calcium absorption in hypercalciuric patients. A group of 18 patients with a specific diagnosis of absorptive hypercalciuria received a dietary supplement of 14 gm. wheat bran at the 2 principal meals for 90 days. A complete assessment of mineral metabolism was performed after 45 and 90 days. Mean basal calciuria was 357 mg. per 24 hours and a significant decrease was noted after 45 days (245 mg. per 24 hours) and 90 days (240 mg. per 24 hours), with a p value of less than 0.01. Urinary oxalate did not vary significantly (0.34 to 0.38 to 0.31 mMol. per 24 hours) and neither did phosphate levels (1,020 to 900 to 893 mg. per 24 hours). A slight and pathologically insignificant decrease was noted in serum iron and urinary magnesium; this fact could be considered a side effect owing to the nonselective binding properties of fiber. Therefore, the positive results achieved confirm the effective action of wheat bran in the treatment of correctly diagnosed absorptive hypercalciuria. .A Tizzani A; Casetta G; Piana P; Vercelli D. .I 202001 .U 90012373 .S J Urol 9001; 142(4):1021-2 .M Adult; Biopsy, Needle/*IS; Human; Male; Spermatogenesis; Testis/*PA. .T Use of biopty gun for transcutaneous testicular biopsies. .P JOURNAL ARTICLE. .W Needle biopsies are being performed commonly as a substitute for open biopsy in certain patients in whom a tissue diagnosis is necessary to determine therapy. During the last few years the Biopty gun and its through-cut needle have evolved as a satisfactory method to perform prostate biopsy in a rapid and painless manner. To determine whether the Biopty gun could be used to perform testicular biopsies 7 patients underwent this procedure in an outpatient setting. The patients received cutaneous lidocaine and the special through-cut needle (already inserted in the gun) was inserted painlessly through this cutaneous wheal towards the tunica albuginea of the testis. The gun was fired and in less than a fraction of a second a biopsy was obtained. The needle was removed and the tissue was placed in Bouin's solution. In some patients more than 1 biopsy was performed. None of the biopsies took more than 5 minutes, none of the patients required postoperative analgesia and none felt untoward discomfort during the biopsy. All biopsies obtained adequate tissue to diagnose the presence of sperm. These results demonstrate that needle biopsy of the testis with the Biopty gun system is a cost-effective, rapid, safe, relatively harmless and effective way to obtain a testicular biopsy to identify the presence of sperm. With time this percutaneous method may supercede other open and percutaneous methods of testicular biopsy. .A Rajfer J; Binder S. .I 202002 .U 90012374 .S J Urol 9001; 142(4):1023 .M Biopsy, Needle/IS/*MT; Equipment Design; Human; Male; Prostate/*PA. .T Prostatic needle biopsy: a simple technique for increasing accuracy [see comments] .P JOURNAL ARTICLE. .A Marshall S. .I 202003 .U 90012375 .S J Urol 9001; 142(4):1024-6 .M Adult; Aged; Bladder/PP; Bladder Diseases/CO/*DT/PP; Circadian Rhythm; Double-Blind Method; Doxepin/AE/*TU; Female; Human; Middle Age; Muscle Contraction; Random Allocation; Sensation; Urinary Incontinence/ET/PP; Urination/DE. .T Doxepin in the treatment of female detrusor overactivity: a randomized double-blind crossover study. .P JOURNAL ARTICLE. .W A total of 19 women with detrusor overactivity and associated symptoms completed a double-blind placebo-controlled crossover study of doxepin. All patients had previously failed to respond to conventional pharmacotherapy. Doxepin was given at bedtime in a single 50 mg. dose for the first 2 weeks and, if needed, the dose was increased with 25 mg. in the morning for the last week of the 3-week treatment period, which was followed by 2 weeks of washout before crossover. The preference for doxepin to placebo was statistically significant (p less than 0.01). Doxepin caused a significant decrease in the nighttime micturition frequency and the nighttime incontinence episodes (p less than 0.05). Urine loss at the standardized 1-hour pad weighing test decreased significantly during treatment with doxepin although statistical significance (p equals 0.07) was not obtained. Cystometric parameters (first sensation and maximum cystometric capacity) improved significantly during treatment with doxepin (p less than 0.06 and less than 0.04, respectively). Side effects were frequent but mild. Suggestions for use of this tricyclic antidepressant in women with detrusor overactivity and possible mechanisms of action are discussed. .A Lose G; Jorgensen L; Thunedborg P. .I 202004 .U 90012377 .S J Urol 9001; 142(4):1032-6 .M Adult; Aged; Biomechanics; Cecum/*SU; Electromyography; Female; Human; Ileum/*SU; Male; Middle Age; Support, Non-U.S. Gov't; Urinary Diversion/*; Urinary Incontinence/PP/*SU; Urodynamics. .T Functional characteristics of the continent ileocecal urinary reservoir: mechanisms of urinary continence. .P JOURNAL ARTICLE. .W We evaluated urodynamically 14 patients with a continent ileocecal urinary reservoir. Reservoirs were constructed of detubularized right colon alone (4 patients), or augmented with ileum (2) or with a U-shaped ileal patch (8). All reservoirs were placed in the abdomen and used plicated terminal ileum as the efferent continence mechanism. Twelve patients are completely continent with intermittent catheterization at 4 to 8-hour intervals. Two patients suffer mild nighttime incontinence. Mean reservoir volume was 675 ml. Intermittent intestinal contractions were noted in the plicated ileal segment and reservoir but they occurred more frequently in the former and were either synchronous with or preceded those in the reservoir. Mean and maximal contraction pressures were 24 and 47 cm. water, respectively, in the reservoir and 40 and 151 cm. water, respectively, in the plicated ileal segment (p equals 0.043 and less than 0.001, respectively). The highest reservoir contractions occurred in the 2 patients with nocturnal incontinence. The method of construction bore no consistent correlation with mean or maximal contraction pressures, contraction frequency or continence. Careful urodynamic assessment suggests that the ileocecal urinary reservoir is a relatively low pressure, nonrefluxing and continent bladder substitute. The plicated terminal ileal segment acts as an effective sphincter that responds to pressure elevations in the reservoir. Its simple construction and easy catheterization make it an attractive alternative to intussuscepted ilea