.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