.I 274229 .U 91000001 .S Am J Emerg Med 9101; 8(5):373-8 .M Abdominal Pain/ET; Adolescence; Adult; Aged; Aged, 80 and over; Appendicitis/CO/*RI/US; Child; Female; Human; Leukocytes/*; Middle Age; Predictive Value of Tests; Support, Non-U.S. Gov't; Technetium Tc 99m Aggregated Albumin/*DU. .T Evaluation of women with possible appendicitis using technetium-99m leukocyte scan. .P JOURNAL ARTICLE. .W The authors evaluated the use of technetium-99m albumin colloid white blood cell (TAC-WBC) scan in women with possible appendicitis. One hundred and nine women underwent 110 TAC-WBC scans. One woman had a second scan on a separate admission and was considered two individual patients in the analysis. Twenty-six women had appendicitis, 10 of whom had a perforated appendix at surgery. The TAC-WBC scan was indeterminate (abnormal but nondiagnostic for appendicitis) in 52 women (47%), nine of whom had appendicitis. Fifty-eight scans were read as positive or negative for appendiceal pathology. There were 16 true positives, 5 false positives, 36 true negatives, and 1 false negative. The predictive value of a positive scan was 76%, and the predictive value of a negative scan was 97%. The TAC-WBC scan was positive in 62% of patients with appendicitis and negative in 43% of the patients without appendicitis resulting in an overall accuracy of 47% in the 109 women. The main value of TAC-WBC scan in women with possible appendicitis is its high negative predictive value and the main problem with the TAC-WBC scan is its high indeterminate rate. .A Henneman PL; Marcus CS; Butler JA; Hall TA; Koci TM; Worthen N; Wilson SE. .I 274230 .U 91000002 .S Am J Emerg Med 9101; 8(5):379-84 .M Accidents/SN; Adolescence; Adult; Aged; California; Case Report; Cause of Death/*; Child; Child, Preschool; Coronary Disease/MO; Emergency Service, Hospital/*SN; Female; Heart Diseases/MO; Homicide/SN; Human; Infant; Male; Middle Age; Retrospective Studies; Suicide/SN; Survival Rate. .T Cause of death in an emergency department [see comments] .P JOURNAL ARTICLE. .W A retrospective review was done of 601 consecutive emergency department deaths. Nontrauma causes accounted for 77% of the deaths and this group had an average age of 64 years and a male to female ratio of 1.9:1. Trauma caused 23% of the fatalities and this group had a younger average age of 29 years and a male to female ratio of 4.6:1. The most common causes of nontrauma death were sudden death of uncertain cause (34%), coronary artery disease (34%), cancer (5%), other heart disease (4%), chronic obstructive lung disease (3%), drug overdose (3%), and sudden infant death syndrome (2%). The most common causes of trauma death were motor vehicle accidents (61%) and gunshot wounds (16%). The overall autopsy rate was 40%. Death certificates were often in error. .A Cummings P. .I 274231 .U 91000003 .S Am J Emerg Med 9101; 8(5):385-7 .M Case Report; Gangrene/TH; Genital Diseases, Male/PA/TH; Human; Hyperbaric Oxygenation/*; Male; Middle Age; Scrotum/*PA. .T Treatment of Fournier's gangrene with adjunctive hyperbaric oxygen therapy. .P JOURNAL ARTICLE. .W Fournier's gangrene is a devastating infection and often is associated with a high morbidity and mortality. Surgical debridement and antibiotics are the cornerstones of therapy. This case describes the use of hyperbaric oxygen as an adjunct in the treatment of Fournier's gangrene. .A Lucca M; Unger HD; Devenny AM. .I 274232 .U 91000004 .S Am J Emerg Med 9101; 8(5):388-90 .M Aged; Case Report; Female; Hernia, Hiatal/*CO/RA; Human; Intestinal Obstruction/*CO/RA; Stomach/*RA. .T Intermittent obstruction of an incarcerated hiatal hernia with a total thoracic stomach. .P JOURNAL ARTICLE. .W A case of intermittent obstruction of a sliding hiatal hernia is presented. The obstruction occurred when the patient's stomach was totally above the diaphragm. The anatomy of sliding hiatal hernias is discussed, as well as the presenting signs and symptoms of obstruction in sliding hiatal hernias. .A Bozzuto TM. .I 274233 .U 91000005 .S Am J Emerg Med 9101; 8(5):391-3 .M Aged; Aged, 80 and over; Arrhythmia/*DI/TH; Case Report; Electrocardiography/*MT; Emergency Service, Hospital; Female; Human; Male; Middle Age; Monitoring, Physiologic/MT. .T Cases in electrocardiography. .P JOURNAL ARTICLE. .A Zimmers T; Geninatti M. .I 274234 .U 91000006 .S Am J Emerg Med 9101; 8(5):394-442 .M Adolescence; Adult; Aged; Aged, 80 and over; Case Report; Child; Child, Preschool; Female; Human; Infant; Male; Middle Age; Poison Control Centers/*; Poisoning/*EP/MO; Population Surveillance; Prevalence; Suicide, Attempted/SN; Survival Rate; United States/EP. .T 1989 annual report of the American Association of Poison Control Centers National Data Collection System. .P JOURNAL ARTICLE. .A Litovitz TL; Schmitz BF; Bailey KM. .I 274235 .U 91000007 .S Am J Emerg Med 9101; 8(5):443-5 .M Adolescence; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Emergency Service, Hospital/*; Female; Human; Infant; Japan; Male; Middle Age; Reproducibility of Results; Ultrasonography/*MT. .T Ultrasonography in Japanese emergency departments. .P JOURNAL ARTICLE. .W This is a review of 50 consecutive cases where ultrasound was performed in the emergency department of a general hospital demonstrating the efficacy of its usage by "nonspecialists." This study demonstrates that in the Japanese model of emergency care delivery, abdominal ultrasound has been shown to be used in the emergency department with accuracy and safety. .A Shapiro RA; Nakamoto M. .I 274236 .U 91000008 .S Am J Emerg Med 9101; 8(5):446-62 .M Wounds and Injuries/*. .T Trauma: an annotated bibliography of the recent literature. .P BIBLIOGRAPHY; JOURNAL ARTICLE. .A McCabe CJ. .I 274237 .U 91000009 .S Am J Emerg Med 9101; 8(5):466-7 .M Administration, Inhalation; Adult; Case Report; Cocaine/*; Human; Male; Pneumothorax/*ET/TH; Substance Abuse/*CO. .T Bilateral spontaneous pneumothorax after cocaine inhalation [letter] .P LETTER. .A Lieberman ME; Shepard H; Reynolds F; Christopher T. .I 274238 .U 91000010 .S Am J Emerg Med 9101; 8(5):467-8 .M Adolescence; Case Report; Ethchlorvynol/*PO; Human; Male; Necrosis/ET; Overdose/PA; Pressure/AE; Skin Diseases, Vesiculobullous/*ET/PA. .T Pressure necrosis following ethchlorvynol overdose [letter] .P LETTER. .A Chamberlain JM; Klein-Schwartz W; Gorman R. .I 274239 .U 91000011 .S Am J Emerg Med 9101; 8(5):468-9 .M Aged; Case Report; Cervical Vertebrae/*IN; Human; Male; Resuscitation/*MT; Wounds, Nonpenetrating/*DI. .T Mismanagement of a potential cervical spine injury [letter; comment] .P COMMENT; LETTER. .A Abarbanell NR. .I 274240 .U 91000012 .S Am J Emerg Med 9101; 8(5):469-70 .M Emergency Service, Hospital/*; Female; Gallbladder Diseases/US; Human; Predictive Value of Tests; Pregnancy; Pregnancy, Ectopic/US; Retrospective Studies; Ultrasonography/*MT. .T Emergency department sonography by emergency physicians [letter; comment] .P COMMENT; LETTER. .A Kellermann AL; Holley J. .I 274241 .U 91000013 .S Am J Emerg Med 9101; 8(5):470-1 .M Amputation/*; Case Report; Compartment Syndromes/*ET/SU; Human; Infant; Infusions, Parenteral/*AE/MT; Ischemia/*ET/SU; Male; Tibia/*BS/SU. .T Compartment syndrome with resultant amputation following intraosseous infusion [letter] .P LETTER. .A Moscati R; Moore GP. .I 274242 .U 91000014 .S Am J Emerg Med 9101; 8(5):472-3 .M Emergencies; Female; Human; Hypertension/*DT; Labetalol/*TU; Male; Middle Age; Pilot Projects; Prospective Studies. .T Ineffectiveness of oral labetalol for hypertensive urgency [letter] .P LETTER. .A Wright SW; Hedges JR; Wright MB; Chudnofsky CR; MacCarthy EP. .I 274243 .U 91000015 .S Pediatr Neurol 9101; 6(4):219-28 .M Age Factors; Amino Acids/*PH; Animal; Brain/*PP; Brain Damage, Chronic/*PP; Cerebral Anoxia/PP; Female; Human; Infant, Newborn; Nerve Regeneration/*PH; Neural Transmission/*PH; Neuronal Plasticity/*PH; Pregnancy; Rats; Receptor, N-Methyl-D-Aspartate/PH; Receptors, Endogenous Substances/*PH; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Excitatory amino acids in the developing brain: ontogeny, plasticity, and excitotoxicity. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Besides their role as neurotransmitters, excitatory amino acids (EAAs) in the developing brain are crucially involved in plasticity and excitotoxicity which are modified by their distinct ontogeny. Along with incomplete neuritogenesis and synaptogenesis, presynaptic markers of the EAA system are immature in the developing brain; however, postsynaptic EAA system activities, particularly of the N-methyl-D-aspartate and quisqualate receptors, are transiently enhanced early in life. This transient enhancement is presumably beneficial to the immature brain because physiologic activation of the EAA system plays a critical role in plasticity of early learning and morphogenesis. At the same time, this transient hypersensitivity renders the immature brain vulnerable to pathologic excitation of the EAA system (excitotoxicity) as observed during neonatal hypoxia-ischemia. .A Hattori H; Wasterlain CG. .I 274244 .U 91000016 .S Pediatr Neurol 9101; 6(4):229-32 .M Asphyxia Neonatorum/DI; Cerebral Hemorrhage/DI; Cerebral Palsy/DI; Cerebral Ventricles/*PA; Follow-Up Studies; Human; Infant; Infant, Newborn; Leukomalacia, Periventricular/*DI; Magnetic Resonance Imaging/*; Meningitis/DI; Sleep Apnea Syndromes/DI; Tomography, X-Ray Computed. .T Periventricular hyperintensity detected by magnetic resonance imaging in infancy. .P JOURNAL ARTICLE. .W Twenty-one infants younger than 12 months of age were diagnosed as having periventricular hyperintensity (PVH) on T2-weighted magnetic resonance imaging. Ten infants had experienced neonatal asphyxia, 6 intracranial hemorrhage, 2 bacterial meningitis, and 3 apnea. PVH was classified according to its extent. Round foci of PVH surrounding the frontal and occipital horns of the lateral ventricles were observed in 4 infants (PVH pattern I). Continuous PVH was observed in 17 infants (PVH patterns II and III). Fourteen infants with continuous PVH had spastic diplegia or quadriplegia. Developmental delay was demonstrated in 15 infants with continuous PVH. No PVH pattern I infants had cerebral palsy; only 1 such infant had mild developmental delay. Our study suggests that the extent of PVH reflects the severity of brain damage in neonates with cerebral injuries. .A Konishi Y; Kuriyama M; Hayakawa K; Konishi K; Yasujima M; Fujii Y; Sudo M. .I 274245 .U 91000017 .S Pediatr Neurol 9101; 6(4):233-9 .M Anencephaly/*PA; Brain/PA; Brain Death/DI/*PA; Human; Infant, Newborn; Neurologic Examination/*; Neurons/PA. .T Anencephaly: clinical determination of brain death and neuropathologic studies. .P JOURNAL ARTICLE. .W Twelve liveborn anencephalic infants were serially examined to determine if they would meet our clinical criteria for whole brain death within a 7-day period: Protocol 1 infants (6) received intensive care including intubation from birth; and Protocol 2 infants (6) received intensive care during the period in which death was imminent. Brain death was determined by absence of brainstem function, including loss of all cranial nerve responses and sustained apnea (PCO2 greater than 60 torr) for 48 hours with confirmation of findings by an outside consulting child neurologist. The initial examinations of these 12 infants revealed spontaneous movements and startle myoclonus (12), suck, root, and gag responses (7), increased tone (8), deep tendon reflexes (9), absent pupillary responses (9), absent oculocephalic and corneal responses (6), absent auditory/Moro responses (7), and nonvisualization of the optic nerve (8). Mild depression of neurologic function occurred during the first several days of life; subsequently, the infants' responses were easier to elicit and more sustained. Only 2 infants met the clinical criteria for brain death. Neuropathologic findings indicated that observed complex motor responses were not based upon cortical activity because no infant had a normally-formed cerebrum. Brainstem neuronal activity may have accounted for these motor responses in some patients but even at this level neurons were scanty or absent. Our findings suggest that, although rare, clinical brain death can be determined in liveborn anencephalic infants; ophthalmologic and otologic developmental abnormalities may confound examination of cranial nerve function; and absence of cortical neurons supports the widely held opinion that these infants do not experience sensation. .A Ashwal S; Peabody JL; Schneider S; Tomasi LG; Emery JR; Peckham N. .I 274246 .U 91000018 .S Pediatr Neurol 9101; 6(4):240-4 .M Adrenocorticotropic Hormone/*AD; Child, Preschool; Dose-Response Relationship, Drug; Electroencephalography/DE; Evoked Potentials/DE; Follow-Up Studies; Human; Infant; Spasms, Infantile/*DT. .T ACTH therapy in infantile spasms: relationship between dose of ACTH and initial effect or long-term prognosis. .P JOURNAL ARTICLE. .W The relationship between the dose of ACTH and the initial effect was investigated in 41 children with infantile spasms. More than 0.015 mg (0.6 IU)/kg/day of ACTH was needed for a good initial response of seizures and electroencephalographic abnormalities. The relationship between the dose of ACTH and long-term prognosis was investigated in 29 patients. There was no relationship between the daily or total ACTH dosage, provided the dose was greater than 0.015 mg (0.6 IU)/kg/day, and the outcome of seizures and electroencephalographic abnormalities; however, ACTH 0.04-0.06 mg (1.6-2.4 IU)/kg/day and a total ACTH dose of 1.1-1.5 mg (44-60 IU)/kg resulted in better mental development than smaller doses of ACTH. Side effects of ACTH increased with dosage. Too small or too large a dose of ACTH does not lead to better mental development. The proper dose of ACTH should be used with careful attention to potential side effects. .A Ito M; Okuno T; Fujii T; Mutoh K; Oguro K; Shiraishi H; Shirasaka Y; Mikawa H. .I 274247 .U 91000019 .S Pediatr Neurol 9101; 6(4):245-50 .M Cerebral Palsy/DI/*PP; Child, Preschool; Female; Follow-Up Studies; Human; Locomotion/*PH; Male; Motor Skills/*PH; Muscle Spasticity/DI/PP; Muscles/PP; Neurologic Examination/*. .T Gross motor patterns in children with cerebral palsy and spastic diplegia. .P JOURNAL ARTICLE. .W Rolling, sitting, and crawling patterns were motoscopically analyzed in 72 children with cerebral palsy and spastic diplegia; the relation between these patterns and the severity of the locomotive disability was studied. In rolling, trunk rotation and elbow support were difficult for the most severely diplegic children. When sitting, most patients had a between-heel sitting pattern in which the thighs were adducted and the knees were flexed. When crawling, the reciprocal thigh movements were insufficient and accompanied by lateral bending of the trunk in many patients. In the more impaired patients, the thighs supported the weight in flexion and did not move reciprocally. Creeping on the elbows without reciprocal leg movements was demonstrated in the most severely affected children after 2 years of age. .A Yokochi K; Hosoe A; Shimabukuro S; Kodama K. .I 274248 .U 91000021 .S Pediatr Neurol 9101; 6(4):257-9 .M Arthrogryposis/DI; Case Report; Child, Preschool; Diagnostic Errors; Electromyography/*; Fasciculation/*DI/GE; Female; Human; Muscles/IR; Myotonia/*DI/GE; Peripheral Nerve Diseases/*DI/GE; Peripheral Nerves/PP; Reaction Time/PH; Syndrome; Tetany/*DI/GE. .T Mistaken diagnoses in continuous muscle fiber activity of peripheral nerve origin. .P JOURNAL ARTICLE. .W The syndrome of continuous muscle fiber activity of peripheral nerve origin has manifestations that resemble those of many other more common neurologic disorders during childhood and infancy. This similarity often leads to misdiagnosis when an adequate index of suspicion is not entertained and a comprehensive electromyographic examination is not performed. Two affected patients from 1 family are reported to illustrate the type of diagnostic errors that were made before the establishment of the correct diagnosis. .A Subramony SH; Parker CC; Evans OB; Hanson RR. .I 274249 .U 91000022 .S Pediatr Neurol 9101; 6(4):260-4 .M Brain/PA; Brain Damage, Chronic/*ET; Brain Edema/ET; Cerebral Ventricles/PA; Child; Child, Preschool; Epilepsy/*ET; Female; Follow-Up Studies; Haemophilus influenzae/*PY; Human; Male; Meningitis, Haemophilus/*CO; Tomography, X-Ray Computed/*. .T Haemophilus influenzae meningitis with prolonged hospital course. .P JOURNAL ARTICLE. .W A retrospective evaluation of Haemophilus influenzae type b meningitis observed over a 2-year period documented 86 cases. Eight of these patients demonstrated an unusual clinical course characterized by persistent fever (duration: greater than 10 days), cerebrospinal fluid pleocytosis, profound meningeal enhancement on computed tomography, significant morbidity, and a prolonged hospital course. The mean age of these 8 patients was 6 months, in contrast to a mean age of 14 months for the entire group. Two patients had clinical evidence of relapse. Four of the 8 patients tested for latex particle agglutination in the cerebrospinal fluid remained positive after 10 days. All patients received antimicrobial therapy until they were afebrile for a minimum of 5 days. Subsequent neurologic examination revealed a persistent seizure disorder in 5 patients (62.5%), moderate-to-profound hearing loss in 2 (25%), mild ataxia in 1 (12.5%), and developmental delay with hydrocephalus which required shunting in 1 (12.5%). One patient had no sequelae. .A Martin LD; Kaplan AM; Rudinsky MF; Frost MD. .I 274250 .U 91000023 .S Pediatr Neurol 9101; 6(4):265-8 .M Biopsy; Case Report; Child; Child, Preschool; Chromosome Abnormalities/DI/*GE; Diagnosis, Differential; Dystrophin/*AN; Fluorescent Antibody Technique; Genes, Recessive/*GE; Human; Male; Muscles/*PA; Muscular Dystrophy/DI/*GE; Support, Non-U.S. Gov't. .T Dystrophin analysis in the differential diagnosis of autosomal recessive muscular dystrophy of childhood and Duchenne muscular dystrophy. .P JOURNAL ARTICLE. .W We report 2 patients with childhood autosomal recessive muscular dystrophy. Both patients had slight muscle weakness without enlargement of the calf muscles or involvement of the facial muscles. Their clinical courses are static. Muscle histology revealed characteristic features of muscular dystrophy. Dystrophin was identifiable in the sarcolemma of both patients by immunocytochemical staining with an antidystrophin antibody. At an early age, immunocytochemical analysis with antidystrophin antibody was useful in distinguishing between childhood autosomal recessive and Duchenne muscular dystrophies. .A Tachi N; Tachi M; Sasaki K; Nagata N; Chiba S. .I 274251 .U 91000024 .S Pediatr Neurol 9101; 6(4):269-71 .M Case Report; Cerebral Cortex/PP; Electroencephalography/*; Evoked Potentials/PH; Female; Follow-Up Studies; Hemolytic-Uremic Syndrome/PP/*TH; Human; Infant; Plasma/*; Status Epilepticus/PP/*TH. .T EEG correlation of improvement in hemolytic-uremic syndrome after plasma infusion. .P JOURNAL ARTICLE. .W We report a previously undescribed electroencephalographic pattern of epochs of diffuse delta background (85-240 sec) alternating with epochs of classic "burst suppression" (90-270 sec) in a 13-month-old girl with hemolytic-uremic syndrome. A dramatic electroencephalographic improvement was evident on continuous monitoring of cerebral function 3 hours after initiating fresh frozen plasma infusion, well before any clinical improvement was apparent. This patient, in addition to the unusual electroencephalographic findings, illustrates the role of continuous electrophysiologic monitoring of cerebral function and supports the use of fresh frozen plasma in hemolytic-uremic syndrome. .A Pascual-Leone A; Dhuna AK; Janousek ST; Talwar D. .I 274252 .U 91000025 .S Pediatr Neurol 9101; 6(4):272-4 .M Adolescence; Biopsy; Case Report; Cerebellar Neoplasms/*DI/PA; Cerebellopontine Angle/*PA; Craniotomy; Female; Human; Lipoma/*DI/PA; Magnetic Resonance Imaging/*; Tomography, X-Ray Computed/*. .T Cerebellopontine angle lipoma in a teenager. .P JOURNAL ARTICLE. .W Lipomas of the cerebellopontine angle are very rare lesions. To date, 18 patients have been reported, 17 of whom were adults. A second child is described with cerebellopontine angle lipoma. .A Ashkenasi A; Royal SA; Cuffe MJ; Aronin PA; Tenorio GM; Benton JW. .I 274253 .U 91000026 .S Pediatr Neurol 9101; 6(4):275-6 .M Adolescence; Case Report; Child; Electromyography/DE; Female; Human; Hypertension, Renal/*DT; Kidney Failure, Acute/CO; Kidney Failure, Chronic/CO; Kidney Transplantation; Labetalol/AD/*AE; Male; Neuromuscular Diseases/*CI; Postoperative Complications/DT. .T Reversible myopathy due to labetalol. .P JOURNAL ARTICLE. .W A severe, generalized myopathy developed in 2 children treated with labetalol. An 11-year-old girl and a 14-year-old boy demonstrated proximal weakness and markedly elevated creatine kinase levels during labetalol therapy. Clinical improvement began immediately when labetalol administration was halted; muscle strength was normal within 2 months. Muscle biopsies were consistent with rhabdomyolysis. .A Willis JK; Tilton AH; Harkin JC; Boineau FG. .I 274254 .U 91000027 .S Pediatr Neurol 9101; 6(4):277-8 .M Blood Coagulation Tests; Case Report; Cerebral Hemorrhage/*BL/DI; Child, Preschool; Factor XIII Deficiency/*CO/DI; Follow-Up Studies; Hematoma, Subdural/BL; Human; Infant; Male; Subarachnoid Hemorrhage/BL; Tomography, X-Ray Computed. .T Factor XIII deficiency and intracranial hemorrhages in infancy. .P JOURNAL ARTICLE. .W We report an infant with Factor XIII deficiency who had 2 seemingly spontaneous intracranial hemorrhages. It is important to consider Factor XIII deficiency as a possible cause of unexplained intracranial hemorrhages in infancy. Ongoing factor replacement therapy is recommended to prevent further bleeding episodes. .A Larsen PD; Wallace JW; Frankel LS; Crisp D. .I 274255 .U 91000028 .S Pediatr Neurol 9101; 6(4):279-81 .M Case Report; Cerebral Angiography; Cerebral Artery Diseases/RA; Chickenpox/*CO/RA; Child; Child, Preschool; Female; Follow-Up Studies; Hemiplegia/*ET/RA; Herpes Zoster Ophthalmicus/CO; Human; Infant; Male; Tomography, X-Ray Computed. .T Varicella with delayed hemiplegia. .P JOURNAL ARTICLE. .W We report 4 children who developed acute hemiplegia 7 weeks to 4 months after varicella infection. In 2 patients, carotid angiography demonstrated segmental narrowing and occlusion of the middle cerebral artery. Their clinical and angiographic features were similar to those associated with contralateral hemiplegia after herpes zoster ophthalmicus, the pathogenesis of which comprises cerebral angiitis due to varicella zoster viral infection. We believe that our patients had the same pathogenesis. In a survey of infectious diseases in our region, the frequency of varicella with delayed hemiparesis was roughly 1:6,500 varicella patients. .A Ichiyama T; Houdou S; Kisa T; Ohno K; Takeshita K. .I 274256 .U 91000029 .S Pediatr Neurol 9101; 6(4):282 .M Cell Line/*; Cerebellar Neoplasms/*PA; Child; Human; Medulloblastoma/*PA; Platelet-Derived Growth Factor/*AN; Radioligand Assay; Tumor Markers, Biological/*AN. .T Medulloblastoma cell line [letter; comment] .P COMMENT; LETTER. .A Whelan HT. .I 274257 .U 91000031 .S Pediatr Neurol 9101; 6(4):283 .M Brain/PA; Child, Preschool; Diagnosis, Differential; Encephalitis Periaxialis/*DI; Human; Infant; Magnetic Resonance Imaging; Male; Multiple Sclerosis/*DI. .T Infantile MS and Schilder disease [letter; comment] .P COMMENT; LETTER. .A Stenager E. .I 274258 .U 91000541 .S Arch Otolaryngol Head Neck Surg 9101; 116(10):1126,1128 .M Animal; Bone Development/*/DE/PH; Bone Transplantation/*; Glycoproteins/PD/PH; Human; Proteins/PD/PH; Rats; Skull/*SU; Transforming Growth Factor beta/PD/PH. .T Osteoinductive implants in head and neck surgery [news] .P NEWS. .A Toriumi DM; Larrabee WF Jr. .I 274259 .U 91000542 .S Arch Otolaryngol Head Neck Surg 9101; 116(10):1128 .M Face/SU; Human; Lasers/*TU; Surgery, Plastic; Wound Healing/*RE. .T Lasers and wound healing [news] .P NEWS. .A Meyers AD. .I 274260 .U 91000543 .S Arch Otolaryngol Head Neck Surg 9101; 116(10):1135-6 .M Communicative Disorders; Deafness; Human; National Institutes of Health (U.S.)/*; Research; United States. .T Message from the National Institutes of Health. The state of the National Institute on Deafness and Other Communication Disorders. .P JOURNAL ARTICLE. .A Snow JB Jr. .I 274261 .U 91000544 .S Arch Otolaryngol Head Neck Surg 9101; 116(10):1137-42 .M Aged; Aging/*PA; Forehead/PA/*SU; Human; Middle Age; Rhytidoplasty/AE/*MT. .T Management of the aging forehead. .P JOURNAL ARTICLE. .W Browlifting and forehead procedures are a critical element in the contemporary surgical management of the aging face. Esthetics of the upper third of the face will dictate brow position and its relationship to the supraorbital rim and eyes. Treatment of deformities of the upper third of the face can be varied according to the sex and age of the patient as well as contour of the hairline and forehead. The indications, advantages, disadvantages, and techniques of the coronal forehead, modified pretrichal forehead, midforehead, and direct browlifting procedures are discussed. .A Kerth JD; Toriumi DM. .I 274262 .U 91000545 .S Arch Otolaryngol Head Neck Surg 9101; 116(10):1143-6 .M Adult; Bacterial Adhesion/*; Child; Epithelium/MI; Haemophilus influenzae/IM/PH; Human; IgA, Secretory/AN; Nasopharynx/*MI; Otitis Media with Effusion/IM/*MI; Streptococcus pneumoniae/IM/PH; Support, Non-U.S. Gov't. .T The role of bacterial adherence in otitis media with effusion. .P JOURNAL ARTICLE. .W Adherence of nontypable Haemophilus influenzae and Streptococcus pneumoniae to nasopharyngeal epithelial cells was investigated in vitro. Both strains had higher affinity to the epithelial cells of children than to those of adults. In children, the adherence was significantly greater in patients with otitis media with effusion than in normal subjects. Secretory IgA in nasopharyngeal secretions was found to have antibody activity against the bacteria. Adherence of both bacteria was significantly smaller in the group having secretory IgA antibody activity than in the group having no activity. These results suggest that bacterial adherence to the nasopharynx may play an important role in the pathogenesis of otitis media with effusion in children, and that secretory IgA in nasopharyngeal secretions may be related to the decrease of adherence. .A Shimamura K; Shigemi H; Kurono Y; Mogi G. .I 274263 .U 91000546 .S Arch Otolaryngol Head Neck Surg 9101; 116(10):1147-53 .M Head/*SU; Human; Neck/*SU; Postoperative Complications; Skin/SU; Tissue Expanders; Tissue Expansion/*/AE/MT. .T Tissue expansion of the head and neck. Indications, technique, and complications. .P JOURNAL ARTICLE. .W Tissue expansion is indicated in the reconstruction of various defects of the head and neck in instances where there is inadequate adjacent tissue to allow either primary closure of the defect or repair with a local flap. It may also be indicated in instances where repair of a defect by an alternative method such as a local, regional, or distant flap will result in an unacceptable donor or recipient site deformity. Although tissue expansion is simplistic in concept, it does require judgment and indepth preoperative planning to ensure optimal results. The complication rate is high for tissue expansion in the head and neck, particularly in the cheek and neck area. Despite the frequency of complications, in the vast majority of cases the intended reconstruction is successful. .A Baker SR; Swanson NA. .I 274264 .U 91000547 .S Arch Otolaryngol Head Neck Surg 9101; 116(10):1154-8 .M Adult; Chin/*SU; Female; Human; Implants, Artificial/*; Male; Middle Age; Phthalic Acids; Polyethylene Glycols; Postoperative Complications; Surgery, Plastic/IS/*MT; Surgical Mesh/*; Surgical Wound Infection. .T Augmentation mentoplasty using Mersilene mesh. .P JOURNAL ARTICLE. .W Many different materials are available for augmentation mentoplasty. However, the optimal implant material for chin implantation has yet to be found. During the past several years, a number of experienced surgeons have turned to the use of Mersilene mesh. Mersilene mesh is a non-absorbable Dacron polyester fiber that can be conformed easily into layers to achieve tailored dimensions and shape. At the McCollough Plastic Surgery Clinic PA, Birmingham, Ala, 277 patients over a 10-year period underwent chin augmentation with Mersilene mesh implants. The material provides excellent tensile strength, durability, and surgical adaptability. The overall complication rate was 3.2% (nine patients); infection rate, 2.5% (seven patients); and removal secondary to infection, 1.7% (five patients). Based on this 10-year experience, Mersilene mesh remains our material of choice for chin augmentation. .A McCollough EG; Hom DB; Weigel MT; Anderson JR. .I 274265 .U 91000549 .S Arch Otolaryngol Head Neck Surg 9101; 116(10):1163-6 .M Alcohol Drinking/AE; Case-Control Studies; Female; Hair Dyes/AE; Human; Male; Middle Age; Mouthwashes/AE; Radiotherapy/AE; Risk Factors; Salivary Gland Neoplasms/*ET; Smoking/AE; Socioeconomic Factors. .T Salivary gland cancer. A case-control investigation of risk factors. .P JOURNAL ARTICLE. .W Unlike most upper aerodigestive tract cancers, salivary gland cancers are relatively infrequent, are characterized by a diversity of histologic subtypes, and have never been etiologically associated with tobacco exposure. We present the results of a case-control study of risk factors for these cancers, with risk estimates derived from self-administered comprehensive risk-factor questionnaires distributed to patients at The University of Texas M. D. Anderson Cancer Center, Houston. Cases were 64 patients with histologically confirmed salivary gland cancer. Control subjects, randomly selected from the same patient population excluding patients with cancer of the head and neck or nonmelanoma skin cancer, were frequency-matched to the cases by age, sex, and ethnicity to achieve a 2:1 control subjects/cases ratio. On multivariate analysis, prior radiotherapy was a significant risk factor for both men (odds ratio [OR] = 2.1) and women (OR = 2.3). Among women, higher educational attainment (OR = 2.4), alcohol use (OR = 2.0), and hairdye use (OR = 2.5) were also significantly associated with risk. There were no significant differences between cases and control subjects with respect to tobacco exposure or specific occupational or leisure-time exposures. There is biological plausibility for associations with hairdye use and alcohol exposure. .A Spitz MR; Fueger JJ; Goepfert H; Newell GR. .I 274266 .U 91000550 .S Arch Otolaryngol Head Neck Surg 9101; 116(10):1167-71 .M Cell Division; Cell Transformation, Neoplastic/PA; Human; Immunoblotting; Intermediate Filament Proteins/AN; Keratin/ME; Laryngeal Neoplasms/ME/MI/*PA; Neoplasm Proteins/ME; Papilloma/ME/MI/*PA; Papillomaviruses/*; Protein Precursors/ME; Stains and Staining; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Thymidine/PK; Tumor Virus Infections/ME/*PA; Uridine/PK. .T Abnormal differentiation of human papillomavirus-induced laryngeal papillomas. .P JOURNAL ARTICLE. .W We studied the proliferation and differentiation of human laryngeal papillomas, which are benign tumors induced by human papillomaviruses. Immunofluorescent stains of tissues for a number of differentiation-specific proteins showed abnormal differentiation. Papilloma tissue fragments in vitro showed a slightly decreased fraction of proliferating cells that incorporated tritiated thymidine and a markedly reduced incorporation of tritiated uridine when compared with normal tissue. We propose that papillomavirus infection results in normal basal cell proliferation but abnormal terminal differentiation and that this abnormality significantly contributes to the hyperplasia of the papillomas. .A Steinberg BM; Meade R; Kalinowski S; Abramson AL. .I 274267 .U 91000551 .S Arch Otolaryngol Head Neck Surg 9101; 116(10):1172-6 .M Animal; Antineoplastic Agents, Combined/*TU; Carcinoma, Squamous Cell/*DT/PA; Cisplatin/AD; Drug Administration Schedule; Drug Interactions; Female; Fluorouracil/AD; Human; Male; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Support, Non-U.S. Gov't. .T Cisplatin-fluorouracil interaction in a squamous cell carcinoma xenograft. .P JOURNAL ARTICLE. .W Patients with squamous cell carcinoma of the head and neck are treated with cisplatin and fluorouracil according to a schedule based on the findings of clinical studies. A similar schedule showed a supra-additive effect in the treatment of xenografted human squamous cell carcinoma of the head and neck. We sought to ascertain whether this schedule was optimal. A single intraperitoneal injection of cisplatin (7.5 mg/kg) was combined with three injections of fluorouracil given during a 24-hour period (total dose, 150 or 80 mg/kg) before, during, or after cisplatin administration. The combined effect of cisplatin and fluorouracil on tumor growth and toxic effects was schedule dependent. Consideration of both toxic effects and tumor growth inhibition, as assessed by reduction of the area under the growth curve, the optimal administration interval was found to be fluorouracil given 3 days after cisplatin administration. .A Rydell R; Wennerberg J. .I 274268 .U 91000552 .S Arch Otolaryngol Head Neck Surg 9101; 116(10):1177-80 .M Animal; Hematoporphyrins/TU; Papillomaviruses/*; Photochemotherapy/*; Porphyrins/TU; Rabbits; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Tumor Virus Infections/*DT/PA; Warts/*DT/MI/PA. .T Laser photodynamic therapy for papilloma viral lesions. .P JOURNAL ARTICLE. .W Photodynamic therapy was tested for its therapeutic efficacy in eradicating rabbit papilloma warts. The wild-type viral warts suspension was used to induce treatable papilloma warts in the cutaneous tissue of Dutch Belted rabbits. The photosensitizing agents used intravenously were Photofrin II at 10 mg/kg of body weight and Chlorin e6 monoethylene diamine monohydrochloric acid (Chlorin e6 med HCl) at 1 mg/kg of body weight. The lasers used were an argon-dye laser at 628 and 655 nm and a gold vapor laser at 628 nm. The irradiances of 25 to 180 mW/cm2 were applied topically with an end-on lens optical fiber with total radiant doses of 7.5 to 54 J/cm2. Photofrin II and the argon-dye laser at the highest light dosage (54 J/cm2) and Chlorin e6 monoethylene diamine monohydrochloride administered 2 hours before argon-dye laser irradiation at 655 nm at the highest light dosage (54 J/cm2) produced wart regression. Total wart regression without recurrence was achieved with Photofrin II and the gold vapor laser at all light dosages. The difference observed between the argon-dye laser and the gold vapor laser might be explained by the pulsed nature of the gold vapor laser, with its high-peak powers, some 5000 x the average measured light dose. In this model, the smaller, less cornified lesions were more effectively treated with photodynamic therapy. .A Go PM; Reed RN; Straight RC; Waner M. .I 274269 .U 91000553 .S Arch Otolaryngol Head Neck Surg 9101; 116(10):1181-5 .M Adult; Aged; Carcinoma, Squamous Cell/*IM/PA; Female; Head and Neck Neoplasms/*IM/PA; Histocompatibility Antigens Class I/*AN; Human; HLA-D Antigens/*AN; Immunoenzyme Techniques; Male; Middle Age; Mucous Membrane/IM. .T HLA class I and class II antigen expression on squamous cell carcinoma of the head and neck. .P JOURNAL ARTICLE. .W We compared human major histocompatibility (HLA) class I and class II antigen expression on squamous cell carcinoma of the head and neck with that on normal mucosa. Frozen sections of a consecutive series of 30 squamous cell carcinomas were stained with the monoclonal antibodies W6/32 (class I) and anti-DR (class II) using an immunoperoxidase technique. Normal mucosa showed class I and class II expression in the basal layers only. Class I expression on tumors was diffuse in 87%, patchy in 10%, and scattered in 3%. Class II expression on tumors was diffuse in 20%, patchy in 53%, scattered in 20%, and absent in 7%. Patterns of expression did not correlate significantly with clinical parameters, including survival, except that class II diffuse and patchy patterns were found to correlate with more poorly differentiated tumors. .A Houck JR; Sexton FM; Zajdel G. .I 274270 .U 91000554 .S Arch Otolaryngol Head Neck Surg 9101; 116(10):1186-9 .M Child; Child, Preschool; Ear, Middle/*PA; Endoscopy/*; Eustachian Tube/PA; Female; Human; Male; Middle Ear Ventilation; Mucous Membrane/PA; Otitis Media with Effusion/*PA/SU; Tympanic Membrane/PA. .T Transtympanic endoscopic findings in patients with otitis media with effusion. .P JOURNAL ARTICLE. .W Using a fine, rigid endoscope (Olympus, SES-1711K), we examined the middle ear, including the tympanic orifice of the eustachian tube, of children with otitis media with effusion (OME) in its active stage (26 ears), in the convalescent stage (13 ears), and during treatment with ventilation tubes for 10 days to 6 months (five ears) through myringotomy with the patients under general anesthesia. Several color photographs of representative ears are shown. In the active stage of OME, edema (73.1%) and hyperemia (23.1%) were characteristic features of the middle ear mucosa, and normal mucosa was seen in only one ear (3.1%). The tympanic orifice of the eustachian tube, which could be examined in 12 ears, were stenosed with edema in four ears (33.3%) or plugged with effusion in three ears (25.0%) in this group. In the convalescent stage of OME, dilated vessels were most often seen (69.2%), but the rest of the patients had normal mucosa (30.8%) in the middle ear, and none of them had edema nor hyperemia. The tympanic orifice of the eustachian tube, which could be examined in five ears, was clearly patent in all the patients in this group. One ear that was treated with a ventilation tube for 1 month showed dilated vessels and less severe inflammation than did ears that were in the active stage of OME, and three ears that were treated for more than 3 months showed almost normal middle ear mucosa. .A Takahashi H; Honjo I; Fujita A; Kurata K. .I 274271 .U 91000555 .S Arch Otolaryngol Head Neck Surg 9101; 116(10):1190-3 .M Comparative Study; False Negative Reactions; False Positive Reactions; Head and Neck Neoplasms/PA; Human; Lymph Nodes/PA/*RA; Lymphatic Metastasis/PA/*RA; Neck; Retrospective Studies; Tomography, X-Ray Computed/*. .T Computed tomography of metastatic cervical lymph nodes. A clinical, computed tomographic, pathologic correlative study. .P JOURNAL ARTICLE. .W A retrospective comparative study of 63 neck dissections was undertaken to evaluate further the accuracy of high-resolution computed tomography (CT) in the detection of nodal metastases, as previous studies have indicated a trend toward the superiority of CT scanning over palpation. The respective values of neck examination, CT scanning, and histopathologic examination were assessed in 51 patients with head and neck cancer who underwent a total of 63 neck dissections. The overall agreement between clinical examination findings and histopathologic findings was 92% vs 81% for CT scanning. A retrospective analysis of the CT findings failed to reveal greater accuracy. We found nodes measuring 10 mm or more with central low density always to be malignant. Because CT scanning seems to offer little advantage over palpation in the nonirradiated neck, it should not be regarded as an essential tool in the staging of nodal disease. After radiation therapy, as neck dissection is only performed because of clinical or radiologic suspicion, CT scanning is of utmost importance. .A Moreau P; Goffart Y; Collignon J. .I 274272 .U 91000556 .S Arch Otolaryngol Head Neck Surg 9101; 116(10):1194-6 .M Adolescence; Child; Ear, External/*AB; Female; Human; Male; Pedigree. .T A survey of accessory auricle anomaly. Pedigree analysis of seven cases. .P JOURNAL ARTICLE. .W We performed an investigation of 50 accessory auricles on subjects encountered during 1983 through 1985. Fifteen of the families were found to have the same accessory auricular deformity among the probands' family members. From these 15 families, we selected seven pedigrees that were not accompanied by auricular deformities who had filial generations for analysis. Pedigrees 1 through 6 showed autosomal dominant inheritance; two also had irregular dominant properties (pedigrees 4 and 7), and one (pedigree 7) could not be excluded from the possibility of having an X-linked recessive inheritance. During the investigation, there were latent accessory auricles in which the cartilages were seen to be subcutaneous only or protruding slightly. Genetically, the pathogenesis of an accessory auricle should be related to the accessory auricular gene. .A Gao JZ; Chen YM; Gao YP. .I 274273 .U 91000557 .S Arch Otolaryngol Head Neck Surg 9101; 116(10):1197-201 .M Adult; Case Report; Female; Human; Implants, Artificial/*; Lip/PA/*SU; Male; Nose/PA; Rhinoplasty/MT; Surgery, Plastic/*MT. .T Significant premaxillary augmentation. .P JOURNAL ARTICLE. .W Substantial premaxillary augmentation is necessary as an adjunctive treatment in most cleft rhinoplasties and in those patients exhibiting an acute nasolabial angle due to retrusion of the premaxila. We describe our technique of evaluation and treatment of this condition using a custom-carved piece of material made from a woven combination of Teflon and organic fibers (Proplast). Detailed technical illustrations as well as patient results are demonstrated. We have found this technique in our hands to be a simple, safe, and effective means of correction of significant premaxillary retrusion. .A Cook TA; Wang TD; Brownrigg PJ; Quatela VC. .I 274274 .U 91000558 .S Arch Otolaryngol Head Neck Surg 9101; 116(10):1202-4 .M Adult; Case Report; Cysts/*/PA/TH; Ear Diseases/PA/TH; Ear, External/*; Human; Male. .T Pseudocyst of the auricle. Case report and world literature review [see comments] .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W We treated a patient with pseudocyst of the auricle and reviewed the 113 cases previously published in the world literature. Pseudocyst of the auricle is an asymptomatic, noninflammatory cystic swelling that involves the anthelix of the ear, results from an accumulation of fluid within an unlined intracartilaginous cavity, and occurs predominantly in men (93% of patients). Characteristically, only one ear is involved (87% of patients), and the lesion is usually located within the scaphoid or triangular fossa of the anthelix. Previous trauma to the involved ear is uncommon. The diagnosis may be suggested by the clinical features, and analysis of the aspirated cystic fluid and/or histologic examination of a lesional biopsy specimen will confirm the diagnosis. Therapeutic intervention that maintains the architecture of the patient's external ear should be used in the treatment of this benign condition. .A Cohen PR; Grossman ME. .I 274275 .U 91000560 .S Arch Otolaryngol Head Neck Surg 9101; 116(10):1208-9 .M Adolescence; Airway Obstruction/DI/*PX; Case Report; Child; Conversion Disorder/*/DI; Female; Human; Male; Respiratory Sounds/ET. .T Functional upper airway obstruction in adolescents. .P JOURNAL ARTICLE. .W Functional upper airway obstruction is an uncommon manifestation of a conversive reaction characterized by recurrent stridor attacks caused by adduction of the vocal cords during inspiration. The oxygen saturation never drops to pathologic levels. The stridor is not accompanied by an appropriate degree of anxiety and is not associated with other symptoms. Patients benefit from verbal reassurance and speech therapy, but stridor attacks tend to recur and psychiatric consultation seems necessary in most cases. We present the case histories of three adolescent patients with nonorganic upper airway obstruction and describe the features that may facilitate the diagnosis of this condition. Early diagnosis and intervention may prevent unnecessary and potentially harmful investigations and therapy. .A Ophir D; Katz Y; Tavori I; Aladjem M. .I 274276 .U 91000561 .S Arch Otolaryngol Head Neck Surg 9101; 116(10):1210-3 .M Adult; Brain Diseases/*ET/MI/RA; Case Report; Human; Hyphomycetes/*; Male; Mucocele/*ET/MI/RA; Mycoses/*CO/RA; Sinusitis/*CO/MI/RA; Tomography, X-Ray Computed. .T Multiple intracranial mucoceles associated with phaeohyphomycosis of the paranasal sinuses. .P JOURNAL ARTICLE. .W The purpose of this article is to alert clinicians to a new pathogenic fungus of the paranasal sinuses called Exserohilum rostratum. Exserohilum species are one of the etiologic agents of phaeohyphomycosis, a constellation of entities caused by dematiaceous fungi. This class of fungal sinus infection has emerged only in the past decade; it occurs primarily in immunocompetent individuals and produces a tenacious, progressive pansinusitis. To our knowledge, this study describes the first case of multiple intracranial mucoceles secondary to E rostratum. The diagnostic workup includes computed tomography and magnetic resonance imaging followed by direct microscopic examination of tissue biopsy specimens. A craniotomy followed by a bilateral external ethmoidectomy was necessary for complete extirpation of the infected mucoceles. Aggressive surgical management of this mycotic infection is described. .A Aviv JE; Lawson W; Bottone EJ; Sachdev VP; Som PM; Biller HF. .I 274277 .U 91000562 .S Arch Otolaryngol Head Neck Surg 9101; 116(10):1214-6 .M Case Report; Child; Cholesteatoma/CN/CO/RA; Ear Diseases/CN/CO/RA; Ear Neoplasms/*/CO/PA/RA; Ear, Middle/*; Human; Male; Osteoma/*/CO/PA/RA; Skull Neoplasms/CO/PA/RA; Temporal Bone/PA/RA. .T Osteoma of the middle ear. Report of a case. .P JOURNAL ARTICLE. .W Osteomas of the middle ear are rare. We report a case of a 7-year-old boy with osteoma originating from the pyramidal eminence, combined with congenital cholesteatoma. The osteoma and cholesteatoma were successfully removed by tympanomastoidectomy. The long process of the incus and the superstructure of the stapes disappeared. The body of the incus was sculpted and used as a columella. Histopathologically, the osteoma was much the same as an external auditory canal osteoma. The possibility of a primary congenital origin of this neoplasm is suggested. .A Yamasoba T; Harada T; Okuno T; Nomura Y. .I 274278 .U 91000563 .S Arch Otolaryngol Head Neck Surg 9101; 116(10):1217 .M Human; Otosclerosis/*DT; Sodium Fluoride/AE/*TU. .T Fluoride therapy for otosclerosis [letter] .P LETTER. .A Shambaugh GE Jr. .I 274279 .U 91000699 .S J Am Soc Echocardiogr 9101; 3(4):255-65 .M Echocardiography/*/*MT; Heart Diseases/*US; Human; Image Processing, Computer-Assisted/*; Observer Variation; Support, U.S. Gov't, P.H.S.. .T Ultrasonic integrated backscatter two-dimensional imaging: evaluation of M-mode guided acquisition and immediate analysis in 55 consecutive patients. .P JOURNAL ARTICLE. .W We have shown previously that cardiac cycle-dependent integrated backscatter characterizes the physical state of myocardium in patients with ischemic heart disease and cardiomyopathy. In the present study the clinical applicability of M-mode guided two-dimensional integrated backscatter imaging was defined in evaluation of 55 nonselected patients. The mean amplitude of cyclic variation of integrated backscatter in normal segments (long-axis view) was as follows: basal septum, 4.2 +/- 1.3 dB (mean +/- SD; n = 27), mid-septum, 4.5 +/- 1.0 dB (n = 26), basal posterior, 4.8 +/- 1.0 dB (n = 30), and mid-posterior, 4.8 +/- 1.2 decibels (n = 27). The respective mean delay values (R wave to nadir) were as follows: 0.89 +/- 0.09, 0.84 +/- 0.09, 0.86 +/- 0.09, and 0.85 +/- 0.12. At least one cardiac cycle could be analyzed fully in 62% of patients. Limitations included technically difficult two-dimensional echocardiography, inadequate M-line orientation, technically remediable errors, or poor quality integrated backscatter images. In abnormal segments (n = 13) cyclic variation was reduced and delay was prolonged (1.2 +/- 1.1 dB and 1.21 +/- 1.1, respectively). Intraobserver and interobserver variability for amplitude measurements were modest, with respective correlation coefficients of r = 0.93; r = 0.72. The findings demonstrate that M-mode--assisted integrated backscatter is a practical approach for characterization of regional myocardial properties promptly and at the bedside in a large portion of patients with cardiac disease. .A Loomis JF Jr; Waggoner AD; Schechtman KB; Miller JG; Sobel BE; Perez JE. .I 274280 .U 91000700 .S J Am Soc Echocardiogr 9101; 3(4):266-75 .M Algorithms/*; Echocardiography/*/*MT; Human; Image Processing, Computer-Assisted/*; Myocardial Contraction/*PH; Support, U.S. Gov't, P.H.S.. .T Applications of cross-correlation techniques to the quantitation of wall motion in short-axis two-dimensional echocardiographic images. .P JOURNAL ARTICLE. .W Echocardiography is now a mainstay in the diagnosis of cardiovascular disease. Rapid methods for quantitation of the images would provide an effective tool for the diagnosis of change in left ventricular function. The purpose of this article is to show the feasibility of using the cross-correlation technique to quantify change in left ventricular function over time in two-dimensional short-axis echocardiographic images. Radial histograms of radial distance versus the number of probable specular targets are formed in eight sectors on each frame during the cardiac cycle. These histograms are then shifted to a position of best correlation. The number of radial bins through which the histograms at end systole are shifted to correlate with those of the frame at end diastole defines the regional motion. The methods are described and preliminary findings are presented. .A Geiser EA; Wilson DC; Gibby GL. .I 274281 .U 91000701 .S J Am Soc Echocardiogr 9101; 3(4):276-84 .M Adult; Analysis of Variance; Comparative Study; Echocardiography/*; Echocardiography, Doppler/*; Female; Graft Rejection; Heart Transplantation/*PH; Human; Male; Observer Variation; Reference Values; Regression Analysis; Reproducibility of Results; Ventricular Function, Left/*PH. .T Variability of Doppler echocardiographic indexes of left ventricular filling in transplant recipients and in normal subjects. .P JOURNAL ARTICLE. .W This study examines the reproducibility and variability of pulsed wave Doppler versus continuous wave Doppler ultrasound indexes of left ventricular filling in cardiac allograft recipients and in normal subjects. The following indexes were studied: isovolumic relaxation time, pressure half-time, peak early mitral flow velocity, and peak mitral flow velocity after atrial systole. Intraobserver and interobserver variability were assessed by regression analysis. Individual components of variance (subject, reader, beat, day, and tracing) were estimated in a subset of five patients and five normal subjects, and estimated total variance defined for each group. Temporal (day-to-day) variability for 95% confidence was estimated for these patients and for normal subjects. Temporal variability in the group from which the subsets were drawn was measured from absolute and percent change in values on two occasions. Estimated and observed 95% confidence limits were compared. Intersubject variability was the largest component of variance in both transplant recipients and in normal subjects. For all indexes in transplant recipients (in the absence of rejection) and normal subjects, observed absolute mean differences (+/- 2 standard deviations) between values from recordings taken on two different days were larger than the 95% confidence limits estimated from the components of variance analysis. The observed 95% limits for transplant recipients versus normal subjects were as follows: isovolumic relaxation time, 20 msec versus 6 msec; pressure half-time, 16 msec versus 9 msec; peak early mitral flow velocity, 32 cm per second versus 17 cm per second; and peak mitral flow velocity after atrial systole, 28 cm per second versus 10 cm per second.(ABSTRACT TRUNCATED AT 250 WORDS) .A Valantine HA; Hatle LK; Appleton CP; Gibbons R; Popp RL. .I 274282 .U 91000702 .S J Am Soc Echocardiogr 9101; 3(4):285-93 .M Aortic Valve Insufficiency/DI/*US; Cardiac Output/PH; Cold/DU; Comparative Study; Echocardiography, Doppler/*; Exercise Test; Female; Human; Male; Middle Age; Nifedipine/DU; Stroke Volume/PH; Support, Non-U.S. Gov't; Vasodilation/DE; Ventricular Function/*PH. .T Left and right ventricular flows by Doppler echocardiography: serial measurements in patients with aortic regurgitation during exercise, cold pressor stimulation, and vasodilation. .P JOURNAL ARTICLE. .W To test the practicality of Doppler echocardiography to measure serial change, biventricular outputs were measured in 15 patients with aortic regurgitation during control periods and during interventions of bicycle exercise, cold pressor stimulation, and vasodilation. Biventricular stroke volumes were measured in 10 normal subjects for validation of methods and differed by 2.8%. Reading errors were 3.7%. Signal quality improved between the first and last observation (p less than 0.05). Velocity signals were corrected for intercept angles, which averaged 12 and 19 degrees for right heart flows and 31 and 32 degrees for the left side of the heart in all subjects. Negative correlations occurred between intercept angles and the chronologic order in which the patients were studied for left (p = 0.02) and right (p = 0.05) flows. Mean flow areas varied 9% in the left ventricle and 20% in the right ventricle. Total variability for measuring flow determined from control values was 11% to 13%. When twice the variability was used as the detectable level of change, only exercise provoked real increases in biventricular flows in the majority of patients. We conclude that serial measurements of flow by Doppler echocardiographic methods had to exceed 20% to 25% to achieve significant change. Measuring intercept angle, resolving flow area, and learning are variables that need greater emphasis. .A Wong M; Matsumura M; Omoto R. .I 274283 .U 91000703 .S J Am Soc Echocardiogr 9101; 3(4):294-302 .M Adult; Aged; Blood Flow Velocity/PH; Cardiomyopathy, Congestive/*US; Comparative Study; Coronary Circulation/PH; Echocardiography; Echocardiography, Doppler/*MT; Human; Middle Age; Support, Non-U.S. Gov't. .T Flow patterns in dilated cardiomyopathy: a pulsed-wave and color flow Doppler study. .P CLINICAL TRIAL; JOURNAL ARTICLE. .W In 48 patients with dilated cardiomyopathy, pulsed-wave and color Doppler examination were performed. In addition, 14 normal patients served as control subjects. Peak inflow velocity at the level of the mitral valve, middle left ventricle, and apex and outflow velocity at the level of the apex, middle left ventricle, and subaortic area were measured. In normal patients there was brisk propagation of inflow velocity to the apex. Patients with dilated cardiomyopathy demonstrated delayed propagation and prolongation of the duration of inflow compared with control subjects (p less than 0.04). Continuous apical flow was visualized in 25% of dilated cardiomyopathies and in no normal patients. Apical velocities were significantly increased in cardiomyopathies with significant mitral regurgitation. Outflow velocities were decreased in dilated cardiomyopathy. In patients with dilated cardiomyopathy and apical dyskinesis, flow directed toward the base was measured in the middle left ventricle during isovolumic relaxation secondary to dyskinetic rebound. Patterns of abnormal flow in dilated cardiomyopathies are readily apparent by color M-mode and two-dimensional color Doppler. .A Jacobs LE; Kotler MN; Parry WR. .I 274284 .U 91000704 .S J Am Soc Echocardiogr 9101; 3(4):303-9 .M Blood Flow Velocity/PH; Coronary Circulation/PH; Echocardiography, Doppler/*MT; Human; Hypertension, Pulmonary/SU/*US; Mitral Valve/*US; Pulmonary Embolism/SU/*US; Ventricular Function, Left/PH. .T Influence of Doppler sample volume location on the assessment of changes in mitral inflow velocity profiles. .P JOURNAL ARTICLE. .W Previous studies that have validated Doppler indexes of mitral inflow have used pulsed wave sample volume locations either at the level of the mitral valve anulus or at the tips of the mitral valve leaflets. Although significant differences between absolute values for peak velocities and velocity time integrals at these sample volume locations have previously been reported, no information exists that has compared changes in inflow profiles after an intervention to improve left ventricular filling. To address this question, 13 patients with severe pulmonary hypertension (mean pulmonary artery pressure, 50 +/- 13 mm Hg) caused by chronic thromboembolic disease were studied with use of Doppler echocardiography immediately before and after surgical reduction of pulmonary hypertension (pulmonary vascular resistance decreased from 916 +/- 413 to 233 +/- 89 dynes.sec.cm5). This clinical model has been shown to have abnormal mitral inflow velocity profiles that improve markedly after surgery. Doppler measures of early and late peak velocities were significantly lower both before and after surgery when sampling at the mitral anulus compared with the leaflet tips, although late filling parameters and the deceleration of early flow velocity tended to differ little. With surgery, the significant increase in peak early velocity and the ratio of early to late velocity was present regardless of the sample volume location (peak E at leaflet tips, 47.1 +/- 16.0 to 68.9 +/- 15.4 [p less than 0.001], and at anulus, 40.7 +/- 11.3 to 56.2 +/- 14.6 cm/sec [p less than 0.001]; peak E/A at leaflet tips, 0.95 +/- 0.4 to 1.55 +/- 0.9, and at anulus, 0.78 +/- 0.3 to 1.32 +/- 0.7 [both p less than 0.02]).(ABSTRACT TRUNCATED AT 250 WORDS) .A Dittrich HC; Blanchard DG; Wheeler KA; McCann HA; Donaghey LB. .I 274285 .U 91000705 .S J Am Soc Echocardiogr 9101; 3(4):310-5 .M Algorithms/*; Blood Flow Velocity; Comparative Study; Computer Graphics/*; Echocardiography, Doppler/*/IS; Human; Image Processing, Computer-Assisted/*. .T Do Doppler color flow algorithms for mapping disturbed flow make sense? .P JOURNAL ARTICLE. .W It has been suggested that a major advantage of Doppler color flow mapping is its ability to visualize areas of disturbed ("turbulent") flow, for example, in valvular stenosis or regurgitation and in shunts. To investigate how various color flow mapping instruments display disturbed flow information, color image processing was used to evaluate the most common velocity-variance color encoding algorithms of seven commercially available ultrasound machines. In six of seven machines, green was reportedly added by the variance display algorithms to map areas of disturbed flow. The amount of green intensity added to each pixel along the red and blue portions of the velocity reference color bar was calculated for each machine. In this study, velocities displayed on the reference color bar ranged from +/- 46 to +/- 64 cm/sec, depending on the Nyquist limit. Of note, changing the Nyquist limits depicted on the color reference bars did not change the distribution of the intensities of red, blue, or green within the contour of the reference map, but merely assigned different velocities to the pixels. Most color flow mapping algorithms in our study added increasing intensities of green to increasing positive (red) or negative (blue) velocities along their color reference bars. Most of these machines also added increasing green to red and blue color intensities horizontally across their reference bars as a marker of increased variance (spectral broadening). However, at any given velocity, marked variations were noted between different color flow mapping instruments in the amount of green added to their color velocity reference bars.(ABSTRACT TRUNCATED AT 250 WORDS) .A Gardin JM; Lobodzinski SM. .I 274286 .U 91000706 .S J Am Soc Echocardiogr 9101; 3(4):316-9 .M Aorta/US; Aortic Valve/US; Aortic Valve Insufficiency/*EP/US; Echocardiography, Doppler/*; Human. .T Prevalence of aortic regurgitation by color flow Doppler in relation to aortic root size. .P JOURNAL ARTICLE. .W To determine whether there is a correlation between aortic root size and the prevalence of aortic regurgitation, we performed color flow Doppler echocardiographic studies on 1015 consecutive patients during a 3-month period. Patients were grouped according to their M-mode aortic root diameter as measured in the left parasternal position. The measured groups ranged from 2.0 to 4.5 cm, grouped at 0.1 cm intervals. As the aortic root size enlarged, the prevalence of aortic regurgitation increased linearly (p less than 0.001; correlation coefficient, r = 0.75). At an aortic root size in the "small normal" range of 2.0 to 2.4 cm, the prevalence of aortic regurgitation was 0% to 15%. In the "intermediate" and "top normal" ranges of 2.9 to 3.7 cm, the prevalence of aortic regurgitation increased linearly from 15% to 47%. With aortic root dilation, the prevalence of aortic root regurgitation was generally more than 50%. The severity of aortic regurgitation was semiquantified. Aortic root size was not a good indicator for the severity of aortic regurgitation. Patients with moderate and severe aortic regurgitation had variable aortic root sizes. Throughout the range of aortic root sizes, mild aortic regurgitation predominated. We conclude that aortic regurgitation is a common finding in patients with aortic roots that are dilated or are in the "top normal" size range, that the prevalence of aortic regurgitation increases linearly with aortic root size, and that aortic root size does not correlate with the severity of aortic regurgitation. .A Seder JD; Burke JF; Pauletto FJ. .I 274287 .U 91000707 .S J Am Soc Echocardiogr 9101; 3(4):320-5 .M Case Report; Double Outlet Right Ventricle/*US; Echocardiography/*; Female; Human; Infant, Newborn. .T Two-dimensional echocardiographic features of double outlet left ventricle. .P JOURNAL ARTICLE; REVIEW; REVIEW OF REPORTED CASES. .W In a cyanotic newborn infant, the diagnosis of double outlet left ventricle was made from the two-dimensional echocardiographic examination. The diagnosis was later confirmed at cardiac catheterization and surgery. The parasternal and subcostal views were especially useful for identification of the origin of both great arteries from the morphologic left ventricle. A review of the medical literature since 1967 revealed 77 cases of double outlet left ventricle, most of which were diagnosed only at surgery or postmortem examination. The anatomic features demonstrated with two-dimensional echocardiography in this case are representative of the findings cited most often in the cases reported in the medical literature. .A Bengur AR; Snider AR; Peters J; Merida-Asmus L. .I 274288 .U 91000708 .S J Am Soc Echocardiogr 9101; 3(4):326-30 .M Aortic Valve Stenosis/*US; Echocardiography, Doppler/*MT; Human. .T Evolution of the continuity equation in the Doppler echocardiographic assessment of the severity of valvular aortic stenosis. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W The use of Doppler techniques has greatly enhanced the noninvasive ultrasound technique for evaluation of valvular aortic stenosis. M-mode and two-dimensional echocardiography could not reliably distinguish patients with severe aortic stenosis from those with milder obstructions. The hemodynamic information offered by Doppler complemented echocardiographic imaging and provided an alternative modality for evaluation of patients with aortic stenosis. By application of the modified Bernoulli equation, the pressure gradient across the stenotic aortic valve could be estimated by Doppler echocardiography. Though helpful and widely used, the information provided by the pressure gradient across the valve about the severity of the obstruction was not complete. The assessment of valvular aortic stenosis therefore includes an estimation of the valve area by application of the continuity equation. This review examines the maturation of the continuity equation by Doppler techniques and discusses the implications of the procedure. .A Taylor R. .I 274289 .U 91000709 .S J Am Soc Echocardiogr 9101; 3(4):331-5 .M Aortic Valve/*US; Aortic Valve Stenosis/US; Blood Flow Velocity/PH; Cardiac Output; Comparative Study; Echocardiography/*; Heart Catheterization; Human; Indicator Dilution Techniques. .T The determination of aortic valve area by the Gorlin formula: what the cardiac sonographer should know. .P JOURNAL ARTICLE. .W The application of the Gorlin formula in the cardiac catheterization laboratory is the standard of reference for the determination of aortic valve area. The continuity equation now enables the cardiac sonographer to determine aortic valve area noninvasively in the echocardiography laboratory. The comparison of the results obtained by the two methods is inevitable. The cardiac sonographer should have a basic understanding of the theory and pitfalls of the Gorlin formula so that when conflicting results are obtained, the possible reasons why will be clear. .A Reynolds T. .I 274290 .U 91000710 .S J Am Soc Echocardiogr 9101; 3(4):336-46 .M Aneurysm, Dissecting/US; Aorta, Abdominal/*US; Aortic Aneurysm/US; Aortic Diseases/*US; Blood Vessel Prosthesis; Echocardiography/*; Human. .T The evaluation of the abdominal aorta: a "how-to" for cardiac sonographers. .P JOURNAL ARTICLE. .W A thorough evaluation of the abdominal aorta can be readily achieved by use of the standard views of the echocardiographic examination. The ultrasound evaluation of the abdominal aorta represents a logical extension of the standard echocardiographic examination of the adult patient. This article provides the information needed to carry out a complete ultrasound examination of the abdominal aorta including the anatomy, the vascular disease, and the steps involved in accomplishing the ultrasound examination of the abdominal aorta. .A Reynolds T; Santos T; Weidemann J; Langenfeld K; Warner MG. .I 274291 .U 91001032 .S Br Heart J 9101; 64(3):174-6 .M Adult; Arrhythmia/PC/PP; Electrocardiography/*; Human; Myocardial Infarction/*DT/PP; Risk Factors; Thrombolytic Therapy/*. .T Late potentials as predictors of risk after thrombolytic treatment? [published erratum appears in Br Heart J 1991 Feb;65(2):113] .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .A Breithardt G; Borggrefe M; Karbenn U. .I 274292 .U 91001034 .S Br Heart J 9101; 64(3):182-5 .M Adult; Age Factors; Aged; Aged, 80 and over; Aspartate Aminotransferase/BL; Creatine Kinase/BL; Electrocardiography; Female; Heart Enlargement/ET; Human; Lactate Dehydrogenase/BL; Logistic Models; Male; Middle Age; Multivariate Analysis; Myocardial Infarction/CO/EN/*MO/PP; Prognosis; Prospective Studies; Risk Factors; Stroke Volume. .T Multivariate analysis in the prediction of death in hospital after acute myocardial infarction. .P JOURNAL ARTICLE. .W Prognostic factors in patients with acute myocardial infarction based on clinical and investigative data on admission were evaluated prospectively in 111 consecutive patients. Seventeen patients (15.3%) died during hospital stay. Age, a previous infarct, high Killip class, cardiomegaly, high serum concentrations of cardiac enzymes, a low ejection fraction, and a high wall motion score index correlated significantly with in-hospital mortality; whereas sex, risk factors, and pericardial effusion did not. Multivariate analysis showed that age and the wall motion score index were the best predictors of death in hospital. Wall motion detected by cross sectional echocardiography may reflect the extent of myocardial involvement. Age and wall motion score index predicted in-hospital mortality with a sensitivity of 76.5%, a specificity of 91.5%, and a predictive accuracy of 89.2%. Age and the wall motion score index can be determined on admission and are useful for identifying patients at high risk of cardiac death who might benefit from early intervention. .A Sahasakul Y; Chaithiraphan S; Panchavinnin P; Jootar P; Thongtang V; Srivanasont N; Charoenchob N; Kangkagate C. .I 274293 .U 91001035 .S Br Heart J 9101; 64(3):186-9 .M Adrenergic Beta Receptor Agonists/*TU; Adult; Aged; Comparative Study; Double-Blind Method; Exercise; Female; Heart Failure, Congestive/*DT/PP; Heart Rate; Human; Male; Middle Age; Propanolamines/*TU; Stroke Volume; Time Factors. .T Ischaemic left ventricular failure: evidence of sustained benefit after 18 months' treatment with xamoterol. .P JOURNAL ARTICLE. .W The long term effects of treatment with xamoterol in 14 patients aged 44-73 with mild to moderate heart failure as a result of ischaemic heart disease are reported. After 18 months' treatment with xamoterol, patients were assessed in a randomised double blind crossover comparison of xamoterol (200 mg twice a day) and placebo, each given for one month. Compared with placebo, xamoterol significantly increased exercise duration and work done on a bicycle ergometer and reduced the maximum exercise heart rate. Assessment of symptoms and activities at 12 months by visual analogue and Likert scales showed a trend towards the relief of symptoms of breathlessness and tiredness and an improvement in activity. There was an improvement in the clinical signs of heart failure and no haemodynamic deterioration over a 12 month period as assessed by ejection fraction. The improvement in exercise tolerance, symptoms, and activities was sustained for 18 months without side effects or development of tolerance. .A Vigholt-Sorensen E; Faergeman O. .I 274294 .U 91001036 .S Br Heart J 9101; 64(3):190-4 .M Adult; Aged; Carcinoid Heart Disease/DI/PA/*US; Echocardiography, Doppler/*; Female; Human; Male; Middle Age; Mitral Valve/PA; Myocardium/PA; Prospective Studies; Support, Non-U.S. Gov't; Tricuspid Valve/PA; Tricuspid Valve Insufficiency/DI/US. .T Transoesophageal echocardiography improves the diagnostic value of cardiac ultrasound in patients with carcinoid heart disease. .P JOURNAL ARTICLE. .W Transthoracic and transoesophageal cardiac echocardiography and Doppler investigations were performed in 31 consecutive patients with malignant midgut carcinoid tumours. The transoesophageal images allowed measurement of the thickness of the atrioventricular valve leaflets and the superficial wall layers on the cavity side of both atria. The mean thickness of the anterior tricuspid leaflet was significantly greater than that of the mitral valve--a difference not seen in a control group of age-matched patients without carcinoid tumours and with normal cardiac ultrasound findings. In addition, the edges of the tricuspid leaflets were thickened giving them a clubbed appearance. Tricuspid incompetence was detected transoesophageally in 71% of the patients with carcinoid compared with 57% by transthoracic investigation. The inner layer of the right atrial wall in the carcinoid patients was significantly thicker than that of the left atrium and that of both atria in the controls. Furthermore, patients with other signs of severe carcinoid heart disease had significantly thicker mean right atrial luminal wall layer than those with less or no signs of right heart disease. Transoesophageal cardiac ultrasound investigation improved the diagnostic accuracy and seemed to show the structural changes typical of carcinoid heart disease established by histopathological investigations. .A Lundin L; Landelius J; Andren B; Oberg K. .I 274295 .U 91001037 .S Br Heart J 9101; 64(3):195-8 .M Adult; Aortic Rupture/CO/*US; Echocardiography/*; Echocardiography, Doppler; Female; Heart Catheterization; Heart Septal Defects, Ventricular/CO/DI; Human; Male; Sinus of Valsalva/*. .T Echocardiographic diagnosis of a ruptured aneurysm of the sinus of Valsalva: operation without catheterisation in seven patients. .P JOURNAL ARTICLE. .W A ruptured aneurysm of the sinus of Valsalva was diagnosed by Doppler, colour, and cross sectional echocardiography in a consecutive series of seven patients. The diagnoses were confirmed at operation without cardiac catheterisation. Examination by pulsed and continuous Doppler echocardiography showed continuous turbulence in six patients with aneurysms rupturing into the right ventricular outflow tract and in the patient with rupture of an aneurysm of the non-coronary sinus into the right atrium. Colour Doppler echocardiography showed turbulent flow across the defects in all seven patients. A ventricular septal defect with aortic regurgitation was detected in one patient and an associated ventricular septal defect in another. Doppler, colour, and cross sectional echocardiography were useful non-invasive techniques for diagnosing a ruptured aneurysm of the sinus of Valsalva without the need for cardiac catheterisation. .A Sahasakul Y; Panchavinnin P; Chaithiraphan S; Sakiyalak P. .I 274296 .U 91001038 .S Br Heart J 9101; 64(3):199-203 .M Adult; Alcohol Drinking; Blood Pressure; Cholesterol/BL; Cluster Analysis; Coronary Disease/BL/*EP/PP; Cross-Sectional Studies; Diet; Female; Human; Lipoproteins, HDL Cholesterol/BL; Male; Middle Age; Risk Factors; Scotland/EP; Smoking/AE; Socioeconomic Factors; Support, Non-U.S. Gov't. .T Geographical clustering of risk factors and lifestyle for coronary heart disease in the Scottish Heart Health Study. .P JOURNAL ARTICLE. .W A large cross sectional study, the Scottish Heart Health Study, of 10,359 men and women from 22 districts of Scotland was undertaken to try to explain the geographical variation of coronary heart disease mortality. Analysis by district showed that of the classic risk factors only cigarette smoking was strongly associated with heart disease mortality among both men and women. Mean diastolic blood pressure was weakly associated with rates among men and high density lipoprotein cholesterol showed a strong negative association among women. Total cholesterol showed a weak negative association with heart disease mortality, but, because the serum concentrations of cholesterol were uniformly high in all districts, a strong association with mortality would not be expected. In both men and women many dietary factors showed moderate or strong associations with mortality from coronary heart disease in a district--of these a low consumption of vitamin C was most notable. Other factors associated with heart disease included alcohol consumption and serum triglycerides among men, and obesity, physical activity, and serum triglycerides among women. Many factors associated with heart disease showed strong intercorrelations. Clustering of risk factors (including smoking, alcohol, and diet among men, and smoking, diet, and obesity among women) was associated with much of the regional variation in heart disease mortality in Scotland. .A Crombie IK; Smith WC; Tavendale R; Tunstall-Pedoe H. .I 274297 .U 91001039 .S Br Heart J 9101; 64(3):204-5 .M Aortic Valve; Aortic Valve Insufficiency/ET/*SU; Arthritis, Infectious/CO; Case Report; Endocarditis, Bacterial/*CO; Female; Heart Valve Prosthesis/*; Human; Infant, Newborn; Staphylococcal Infections/CO. .T Replacement of an aortic valve cusp after neonatal endocarditis. .P JOURNAL ARTICLE. .W Septic arthritis developed in a neonate after an infection of her hand. Despite medical and surgical treatment endocarditis of her aortic valve developed and the resultant regurgitation required emergency surgery. At operation a new valve cusp was fashioned from preserved calf pericardium. Nine years later she was well and had full exercise tolerance with minimal aortic regurgitation. .A Tulloh RM; Silove ED; Abrams LD. .I 274298 .U 91001040 .S Br Heart J 9101; 64(3):206-7 .M Adult; Cardiac Tamponade/*CO/TH; Case Report; Drainage; Human; Hyponatremia/*ET; Inappropriate ADH Syndrome/*CO; Male; Paraplegia/CO; Pulmonary Embolism/PC; Warfarin/TU. .T Hyponatraemia secondary to an inappropriately high release of antidiuretic hormone in cardiac tamponade. .P JOURNAL ARTICLE. .W A spontaneous intrapericardial haemorrhage caused cardiac tamponade in a 29 year old paraplegic man who was being treated with warfarin. The associated persistent hyponatraemia, which was believed to be caused by an inappropriately high release of antidiuretic hormone, rapidly resolved after pericardiocentesis. .A Groves PH; Shah AM; Hutchison SJ. .I 274299 .U 91001041 .S Br Heart J 9101; 64(3):208-10 .M Aged; Case Report; Coronary Vessel Anomalies/CO/*SU/US; Death, Sudden/*ET; Echocardiography; Human; Male; Mitral Valve Prolapse/CO/SU; Resuscitation. .T Aberrant origin of the right coronary artery as a potential cause of sudden death: successful anatomical correction. .P JOURNAL ARTICLE. .W A man with an aberrant right coronary artery and haemodynamically important prolapse of the mitral valve was successfully resuscitated. The aberrant right coronary artery was thought to be a possible cause of the cardiopulmonary arrest in this patient. Both lesions were corrected at a single operation. .A Nelson-Piercy C; Rickards AF; Yacoub MH. .I 274300 .U 91001042 .S Br Heart J 9101; 64(3):211-3 .M Angina Pectoris/ET; Coronary Vessels/*RA; Female; Heart Arrest/ET; Heart Catheterization/AE/*IS; Human; Male; Middle Age. .T Cardiac catheterisation with 5 French catheters. .P JOURNAL ARTICLE. .W From the beginning of November 1987 to the end of January 1989, 526 coronary arteriograms and left ventricular angiograms were performed with 5 French coronary catheters. In 448 (85%) patients diagnostic pictures were obtained with three standard types of 5 French catheters (No 4 Judkins): that is, left coronary, right coronary, and pigtail catheters. In 60 patients (11.4%) various other 5 French catheters were required to complete the study. In nine patients (1.7%), a 7 or 8 French catheter was used. Major complications causing cardiac arrest or requiring urgent operation developed in five patients. Sixty two patients (11.77%) had minor complications that required sublingual nitrates or a single bolus of atropine, or developed a haematoma that did not need intervention or had a mild reaction to the contrast material. Complications of moderate severity developed in 17 patients (3.2%): severe chest pain, arrhythmia requiring a temporary pacemaker, contrast reaction associated with hypotension, haematoma requiring blood transfusion, or a transient ischaemic episode. There were no deaths. 5 French catheters were used for routine coronary angiography and left ventriculography in 98.3% of patients. There were no major complications related to femoral artery puncture. The routine use of 5 French coronary catheters should increase the feasibility of safe coronary angiography in outpatients and should reduce the cost of this investigation. .A O'Sullivan JJ; McDonald K; Crean PA; Walsh MJ; McCarthy C; Erwin RJ; Maurer BJ. .I 274301 .U 91001043 .S Br Heart J 9101; 64(3):214-8 .M Adolescence; Adult; Aged; Cardiomyopathy, Congestive/PP/US; Child; Comparative Study; Echocardiography/*; Echocardiography, Doppler/*; Female; Heart Enlargement/PP/US; Human; Male; Middle Age; Mitral Valve/PP/US; Mitral Valve Stenosis/PP/US; Myocardial Infarction/PP/*US; Phonocardiography; Time Factors. .T Discrepancies in the measurement of isovolumic relaxation time: a study comparing M mode and Doppler echocardiography. .P JOURNAL ARTICLE. .W Mitral valve cusp separation on M mode echogram, the mitral valve opening artefact, and the onset of forward transmitral flow recorded by Doppler echocardiography have all been taken to mark the end of isovolumic relaxation, while its onset has been taken either as the aortic closure sound (A2) recorded phonocardiographically or the aortic closure artefact determined by Doppler technique. Possible differences in the measurement of the isovolumic relaxation time were studied when these landmarks were used in 44 healthy people, 14 patients with mitral stenosis, 21 patients with left ventricular hypertrophy, and 24 patients with dilated cardiomyopathy by recording M mode echograms of the mitral valve, and pulsed and continuous wave Doppler spectra of transmitral flow, with simultaneous electrocardiograms and phonocardiograms. A2 was effectively synchronous with the aortic artefact. However, when the onset of Doppler flow was regarded as the end of isovolumic relaxation, the interval was significantly longer than when mitral cusp separation on M mode echograms was used: by 25 (10) ms in healthy individuals, by 25 (15) ms in patients with left ventricular hypertrophy, and by 50 (35) ms in patients with dilated cardiomyopathy. In patients with mitral stenosis the interval was only 5 (5) ms longer. The mitral valve opening artefact consistently followed the onset of flow and corresponded much more closely to the E point on the M mode echogram. This shows that it occurred during the rapid filling period and well beyond isovolumic relaxation by any definition. Thus isovolumic relaxation time measured from A2 to the onset of transmitral flow or the mitral valve opening artefact differs from that derived from A2 to mitral valve cusp separation. These intervals cannot be used interchangeably to measure "isovolumic relaxation time". .A Lee CH; Vancheri F; Josen MS; Gibson DG. .I 274302 .U 91001044 .S Br Heart J 9101; 64(3):219-22 .M Aged; Cardiology/*/EC; Great Britain; Health Care Rationing/*EC; Health Resources/SD; Heart Surgery/EC; Human; State Medicine. .T Can rationing of cardiological services be rational? .P JOURNAL ARTICLE. .A Chamberlain D; Alderslade R. .I 274303 .U 91001045 .S Br Heart J 9101; 64(3):223-6 .M Correspondence; Electrocardiography/HI; England; Germany; History of Medicine, 20th Cent.; Netherlands; Physiology/*HI; USSR. .T The last portrait of Willem Einthoven: newly discovered links between Sir Thomas Lewis and Alexander Samojloff. .P HISTORICAL ARTICLE; HISTORICAL BIOGRAPHY; JOURNAL ARTICLE. .A Krikler DM; Hollman A. .I 274304 .U 91001046 .S Br Heart J 9101; 64(3):227 .M Human; Middle Age; Myocardial Infarction/*MO; Risk Factors; Systole/PH; Time Factors. .T Estimation of the risk of death after acute myocardial infarction from systolic time intervals [letter; comment] .P COMMENT; LETTER. .A Weissler AM. .I 274305 .U 91002375 .S Br J Dermatol 9101; 123(3):283-9 .M Administration, Topical; Adolescence; Adult; Epidermis/*DE/ME; Human; Immunoblotting; Immunoenzyme Techniques; Interleukin-1/*ME; Middle Age; Protein Precursors/ME; Support, Non-U.S. Gov't; Tretinoin/AD/*PD. .T Effect of topical retinoic acid on the interleukin 1 alpha and beta immunoreactive pool in normal human epidermis. .P JOURNAL ARTICLE. .W The topical application of 0.1% retinoic acid (RA) on human skin over a period of 4 days, whether or not under occlusion, did not increase either IL-1 alpha or beta immunoreactivity as determined by a sensitive enzymoimmunoassay. No down modulation was seen following the application of a potent topical corticosteroid. Occlusion increased the yield of IL-1 beta immunoreactivity. Immunoblot patterns of epidermal extracts revealed both the mature form of IL-1 (17 kDa) and the precursor (36 kDa) and were identical in amounts whether the specimens were from controls or from RA- or corticosteroid-treated skin. There was a slight modification in the pattern of high molecular weight proteins (52 kDa) probed by the anti-IL-1 alpha and beta sera. It appears that the IL-1 epidermal immunoreactive pools are barely amenable to modulation because they represent a storage form linked to end-stages of keratinocyte differentiation. .A Gruaz DC; Didierjean L; Gumowski-Sunek D; Saurat JH. .I 274306 .U 91002376 .S Br J Dermatol 9101; 123(3):291-5 .M Adult; Aged; Antibodies, Monoclonal/ME; Betamethasone/*TU; Calcitriol/*AA/TU; Comparative Study; Double-Blind Method; DNA/*AN; Female; Fluorescent Antibody Technique; Human; Keratin/IM/*ME; Male; Middle Age; Psoriasis/*DT/ME; Skin/ME. .T DNA content and Ks8.12 binding of the psoriatic lesion during treatment with the vitamin D3 analogue MC903 and betamethasone. .P CLINICAL TRIAL; JOURNAL ARTICLE. .W Twenty patients with psoriasis were treated with the vitamin D3 analogue MC903 and betamethasone ointment in a double-blind trial with a left-right comparison. In addition to the clinical severity scores, Ks8.12 binding which detects keratin 16 expression and the DNA synthesis were quantified using flow cytometry. Both markers decreased significantly with treatment, but remained above the normal range even in those who had total clearance of the lesions. Treatment with MC903 with regard to Ks8.12 binding was significantly better than with betamethasone. .A de Mare S; de Jong EG; van de Kerkhof PC. .I 274307 .U 91002377 .S Br J Dermatol 9101; 123(3):297-304 .M Adult; Aged; Aged, 80 and over; Cell Movement/DE; Cytokines/*AN; Exudates and Transudates/*IM; Female; Human; Interleukin-1/*AN/PD; Interleukin-6/*AN; Lymphocytes/DE; Male; Middle Age; Mycosis Fungoides/*IM; Skin Neoplasms/*IM; Support, Non-U.S. Gov't. .T Skin exudate levels of interleukin 6, interleukin 1 and other cytokines in mycosis fungoides. .P JOURNAL ARTICLE. .W The role of locally released cytokines in inducing lymphocyte activation and infiltration in the skin lesions of mycosis fungoides has been investigated. The levels of selected cytokines were measured in chamber fluid samples from lesional and control skin. Biologically active interleukin 6 was significantly elevated in lesional samples and a recombinant form of this cytokine was shown to induce lymphocyte migration in an in vitro assay. Biologically active interleukin 1 was detected in all control chamber fluid samples. Significantly reduced levels of this cytokine were present in lesional samples, which may be the result of the release of preformed material. Interleukin 2 and tumour necrosis factor activity, and gamma interferon and granulocyte macrophage colony-stimulating factor immunoreactivity, were not detectable in any of the samples. Interleukins 1 and 6 may play a role in the pathogenesis of the lesional lymphocyte infiltrates in mycosis fungoides. .A Lawlor F; Smith NP; Camp RD; Bacon KB; Black AK; Greaves MW; Gearing AJ. .I 274308 .U 91002378 .S Br J Dermatol 9101; 123(3):305-12 .M Adult; Aged; Arthritis, Rheumatoid/DT/PA; Drug Administration Schedule; Elastic Tissue/*DE/PA; Female; Human; Joints/DE; Male; Middle Age; Penicillamine/AD/*AE/TU; Prevalence; Pseudoxanthoma Elasticum/CI/PA; Skin/DE/PA. .T Elastic fibre damage induced by low-dose D-penicillamine. .P JOURNAL ARTICLE. .W We have studied 23 patients receiving penicillamine for the treatment of rheumatoid arthritis to determine the prevalence of penicillamine-induced elastosis. One female patient had pseudoxanthoma elasticum-like skin changes and bramble-bush elastosis without calcification in the involved skin. Penicillamine elastosis was present in the joint capsule in 62% of eight patients or 64% of II joints examined and was detected in joint capsules after as little as I year of treatment. .A Dalziel KL; Burge SM; Frith PA; Ryan TJ; Mowat A. .I 274309 .U 91002379 .S Br J Dermatol 9101; 123(3):313-8 .M Basement Membrane; Cell Movement/PH; Chemotaxis/PH; Connective Tissue; Fibroblasts/CY; Human; Male; Neoplasm Invasiveness; Sarcoma, Kaposi's/*PA; Skin Neoplasms/*PA; Support, Non-U.S. Gov't; Tumor Cells, Cultured/DE/PA; Tumor Necrosis Factor/PD. .T Invasive migration of epidemic Kaposi's sarcoma cells in vitro. .P JOURNAL ARTICLE. .W Kaposi's sarcoma (KS) is a low grade malignant neoplasm which shows invasive growth and often occurs in immunosuppressed patients with the Acquired Immune Deficiency Syndrome (AIDS; epidemic KS). It is also found in elderly men where it is usually limited to the skin (classic KS). The present study investigated the chemotaxis and invasive migration of epidemic KS cells in vitro and compared them to cells grown from classic KS lesions and to fibroblasts. Epidemic KS cells demonstrated invasive migration through reconstituted basement membrane (Matrigel) as well as through interstitial connective tissue (collagen I) in early passages, whereas fibroblasts did not invade either barrier. Epidemic KS cells in late passages did not show any invasive migration. Following pretreatment with tumour necrosis factor alpha (TNF-alpha) there was no enhanced migration through the Matrigel and collagen I for epidemic KS cells, whereas classic KS cells showed an increased migration through the type I collagen barrier. .A Schirren CG; Roth WK; Hein R; Werner S; Krieg T; Braun-Falco O. .I 274310 .U 91002380 .S Br J Dermatol 9101; 123(3):319-23 .M Adult; Aged; Comparative Study; Female; Human; Male; Middle Age; Neutrophils/*CH; Psoriasis/BL/*ME; Seborrhea/BL/*ME; Support, Non-U.S. Gov't; Zinc/*AN/BL. .T Neutrophil zinc levels in psoriasis and seborrhoeic dermatitis. .P JOURNAL ARTICLE. .W The median zinc content of neutrophils was significantly reduced in 16 patients with psoriasis in comparison to both normal controls and six patients with seborrhoeic dermatitis (P less than 0.05). This reduction was unrelated to the extent of skin involvement. Plasma and erythrocyte zinc levels were unchanged. .A Leung RS; Turnbull AJ; Taylor JA; Russell-Jones R; Thompson RP. .I 274311 .U 91002381 .S Br J Dermatol 9101; 123(3):325-31 .M Culture Media; Dermatitis, Atopic/IM; Human; Immunity, Cellular/IM; Leukocyte Culture Test, Mixed/*; Psoriasis/*IM; Support, Non-U.S. Gov't; T-Lymphocytes/*IM. .T Autologous mixed lymphocyte reaction is reduced in patients with psoriasis. .P JOURNAL ARTICLE. .W The autologous mixed lymphocyte reaction (auto-MLR) was studied to test the interactions between immunocompetent cells in patients with psoriasis. The auto-MLR in 20 patients with psoriasis was significantly lower than in 16 normal controls. Lower values were found in untreated psoriatic patients than in those in remission following treatment. The values in the latter group were significantly lower than in controls and in six patients with atopic dermatitis in remission. The tendency for an increase in the auto-MLR with a decrease in disease activity was further confirmed in five patients studied before and after treatment. In contrast, the allogeneic lymphocyte reaction (allo-MLR) in psoriatics was similar to that in normal controls. .A Terui T; Rokugo M; Aiba S; Kato T; Tagami H. .I 274312 .U 91002383 .S Br J Dermatol 9101; 123(3):339-46 .M Cell Division/DE; Collagen/BI; Depression, Chemical; Fibroblasts/DE/ME; Fibronectins/BI; Glycosaminoglycans/BI; Human; Keloid/ME; Pentoxifylline/*PD; Scleroderma, Circumscribed/ME; Scleroderma, Systemic/ME; Skin/*DE/ME; Skin Diseases/*ME; Support, U.S. Gov't, Non-P.H.S.. .T Pentoxifylline inhibits the proliferation of human fibroblasts derived from keloid, scleroderma and morphoea skin and their production of collagen, glycosaminoglycans and fibronectin. .P JOURNAL ARTICLE. .W Pentoxifylline, an analogue of the methylxanthine theobromine, inhibits the proliferation and certain biosynthetic activities of fibroblasts derived from normal human skin. Fibroblasts from the skin of patients with keloids, scleroderma and morphoea were cultured in vitro in the presence and absence of pentoxifylline (100-1000 micrograms/ml) to determine whether it inhibits fibroblast proliferation and the production of collagen, glycosaminoglycans (GAG), fibronectin and collagenase activity. The exposure of subconfluent fibroblast cultures to pentoxifylline resulted in non-lethal, dose-dependent reductions in serum-driven fibroblast proliferation, with 1000 micrograms/ml pentoxifylline virtually negating the proliferative effect of serum on the cells. The fibroblasts assayed as confluent cultures produced reduced amounts, by up to 95%, of collagen and GAG, dependent on the concentration of pentoxifylline, both in the presence and absence of serum. Pentoxifylline similarly inhibited the fibronectin production by keloid and scleroderma fibroblasts, but had no effect on collagenase activity. .A Berman B; Duncan MR. .I 274313 .U 91002384 .S Br J Dermatol 9101; 123(3):347-53 .M Alkaline Phosphatase/BL; Creatinine/BL; Cyclosporins/AD/*AE; Dose-Response Relationship, Drug; Drug Administration Schedule; Human; Hypertension/*CI; Kidney/*DE; Middle Age; Psoriasis/BL/*DT/EN; Time Factors. .T Analysis of side-effects of medium- and low-dose cyclosporin maintenance therapy in psoriasis. .P JOURNAL ARTICLE. .W The side-effects of long-term cyclosporin A (CyA) treatment in 26 patients with severe psoriasis were evaluated. These patients had a mean PASI score of 30.2 and were treated with CyA for between 7 and 37 months (mean 19.5 months). There were three groups according to the dose of CyA, less than 2 mg/kg per day, 2-3 mg/kg per day and greater than 3 mg/kg per day. In all three groups, CyA was found to be equally effective. Treatment with CyA was discontinued in 12 of the 26 patients because of nephrotoxicity and/or development of hypertension. One was in the less than 2 mg/kg per day group, three were in the 2-3 mg/kg per day group and eight in the greater than 3 mg/kg per day group. There was no hepatotoxicity with CyA treatment. One patient developed two squamous cell carcinomas of the skin. .A de Rie MA; Meinardi MM; Bos JD. .I 274314 .U 91002386 .S Br J Dermatol 9101; 123(3):365-73 .M Adult; Female; Human; Male; Nails/AH/*US; Ultrasonics; Water/*. .T Ultrasound velocity in human fingernail and effects of hydration: validation of in vivo nail thickness measurement techniques. .P JOURNAL ARTICLE. .W Distal nail thickness was measured using an electronic micrometer and both distal and proximal nail ultrasound times were recorded in 20 volunteers (10 male, 10 female), aged 20-39. The fingernail ultrasound velocity was 2.26 X 10(3) m/s (subject range 2.03-2.69) (analysis of variance technique). The proximal ultrasound transit time was greater than distal ultrasound transit time. In three volunteers, five micrometer and one distal midline ultrasound measurement of five nails were repeated on 10 occasions over 2 weeks. For the micrometer readings the average coefficient of variation was 5.3% (SD +/- 2.4%), and for the ultrasound reading the average coefficient of variation was 4.0% (SD +/- 1.3%). To assess the influence of hydration, in five volunteers the distal nail micrometer thickness and the distal nail ultrasound transit time were measured on five nails before and after 30 min of immersion in water initially at 37 degrees C. The mean distal ultrasound transmission time increased from 0.20 +/- 0.04 microseconds to 0.22 +/- 0.04 microseconds (P less than 0.001) after water immersion. The micrometer measurements and ultrasound velocity did not change significantly (mean ultrasound velocity = 2.01 X 10(3) m/s before, 2.04 X 10(3) m/s after immersion). .A Finlay AY; Western B; Edwards C. .I 274315 .U 91002388 .S Br J Dermatol 9101; 123(3):381-7 .M Adult; Arginine/*AD/TU; Feces/CH; Female; Heme/*AD/TU; Human; Infusions, Intravenous; Photosensitivity Disorders/DT; Porphyria/BL/*DT; Protoporphyrins/AN/BL; Skin/DE; Skin Diseases/*DT; Support, Non-U.S. Gov't. .T Effects of haem arginate on variegate porphyria. .P JOURNAL ARTICLE. .W Four patients with variegate porphyria (VP) were treated with repeated haem arginate infusions daily for 4 days and then weekly for 4 weeks. After the initial four daily doses of haem arginate (haem 3 mg/kg), the excretion of faecal protoporphyrin (mean 579 nmol/g dry wt) fell to an almost normal level (mean 123 nmol/g dry wt), and that of coproporphyrin (mean 162 nmol/g dry wt) to the normal level (mean 21 nmol/g dry wt) in all patients. However, during the period of the four weekly infusions of haem the excretion of porphyrins increased almost to the pretreatment level. Phototesting showed no changes in the photoreactivity of the skin, and no improvement in skin lesions was seen during the treatment. Except for one case of thrombophlebitis no side-effects occurred. In a child with homozygous VP, four daily infusions of haem arginate (2 mg/kg) normalized the faecal protoporphyrin content, but had no effect on the increased erythrocyte protoporphyrin concentration. .A Timonen K; Mustajoki P; Tenhunen R; Lauharanta J. .I 274316 .U 91002389 .S Br J Dermatol 9101; 123(3):389-93 .M Case Report; Drug Therapy, Combination; Gangrene; Human; Injections, Intravenous; Male; Mezlocillin/*AD/TU; Middle Age; Pyoderma/*DT; Vancomycin/*AD/TU. .T Successful treatment of eruptive pyoderma gangrenosum with intravenous vancomycin and mezlocillin. .P JOURNAL ARTICLE. .A Kang S; Dover JS. .I 274317 .U 91002390 .S Br J Dermatol 9101; 123(3):395-401 .M Adult; Case Report; Female; Gangrene; Human; Male; Metabolism, Inborn Errors/*PA; Receptors, Leukocyte-Adhesion/*DF; Skin/PA; Skin Ulcer/*ME/PA. .T Skin manifestations in congenital deficiency of leucocyte-adherence glycoproteins (CDLG). .P JOURNAL ARTICLE. .W In congenital deficiency of leucocyte-adherence glycoproteins (CDLG) there is an immunodeficiency with impaired leucocyte function and cutaneous and extracutaneous infections occur. In more than 30% of cases the condition has a fatal course. We report the skin manifestations of three siblings with CDLG in which areas of skin necrosis occurred that resembled pyoderma gangrenosum. .A van de Kerkhof PC; Weemaes CM. .I 274318 .U 91002391 .S Br J Dermatol 9101; 123(3):403-7 .M Adolescence; Argyria/*ET/PA; Case Report; Female; Foreign Bodies/*CO; Human; Skin/*PA/UL. .T An unusual case of acquired localized argyria. .P JOURNAL ARTICLE. .W We report an unusual cause of localized cutaneous argyria, due to the cutaneous implantation of a silver earring back. .A Shall L; Stevens A; Millard LG. .I 274319 .U 91002392 .S Br J Dermatol 9101; 123(3):409-12 .M Case Report; Colon/PA; Crohn Disease/*CO/IM/PA; Female; Human; HLA Antigens/AN; Lip/PA; Melkersson-Rosenthal Syndrome/*CO/IM/PA; Middle Age; Rectum/PA. .T Granulomatous cheilitis and Crohn's disease. .P JOURNAL ARTICLE. .A Kano Y; Shiohara T; Yagita A; Nagashima M. .I 274320 .U 91002393 .S Br J Dermatol 9101; 123(3):413-4 .M Adult; Case Report; Human; Male; Mucocutaneous Lymph Node Syndrome/*PA; Perineum/*PA; Skin/*PA. .T Kawasaki disease in a young adult with a perineal rash [letter] .P LETTER. .A Machet L; Vaillant L; Goutal H; Lanternier G; Khallouf R; Chagnon JL; Lorette G. .I 274321 .U 91002394 .S Br J Dermatol 9101; 123(3):414-5 .M Baths/AE; Case Report; Human; Male; Middle Age; Myelodysplastic Syndromes/*CO; Pruritus/*ET; Water/*AE. .T Aquagenic pruritus and the myelodysplastic syndrome [letter] .P LETTER. .A McGrath JA; Greaves MW. .I 274322 .U 91002395 .S Br J Dermatol 9101; 123(3):415-6 .M Adult; Alopecia/DT; Case Report; Cyclopropanes/*AE; Human; Male; Vitiligo/*CI. .T Persistent vitiligo induced by diphencyprone [letter] .P LETTER. .A Duhra P; Foulds IS. .I 274323 .U 91002875 .S Blood 9101; 76(7):1267-8 .M Bleomycins/TO/TU; Cyclophosphamide/TO/TU; Etoposide/TO/TU; Human; Lymphoma, Large-Cell, Diffuse/*DT/MO; Prednisone/TO/TU; Procarbazine/TO/TU. .T Salvage therapy for diffuse large-cell lymphoma [editorial] .P EDITORIAL. .A Chabner BA. .I 274324 .U 91002876 .S Blood 9101; 76(7):1269-80 .M Human; Immunogenetics; Minor Histocompatibility Antigens/AN/*IM/PH; Support, Non-U.S. Gov't; Transplantation Immunology. .T Minor histocompatibility antigens. .P JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC. .A Perreault C; Decary F; Brochu S; Gyger M; Belanger R; Roy D. .I 274325 .U 91002877 .S Blood 9101; 76(7):1281-6 .M Antigens, Differentiation/*AN; Blood Cells/CH/MI; Bone Marrow/CH/CY/MI; Cell Count; DNA, Viral/AN; Hematopoietic Stem Cells/CH/*IM/MI; Human; HIV-1/GE/*IP; Polymerase Chain Reaction; Support, Non-U.S. Gov't. .T CD34+ hematopoietic progenitor cells are not a major reservoir of the human immunodeficiency virus. .P JOURNAL ARTICLE. .W Hematologic abnormalities occur in the majority of patients with acquired immunodeficiency syndrome (AIDS). Infection of the hematopoietic progenitor cells has been proposed as a potential explanation. In this study, different bone marrow cell populations, including the CD34+ hematopoietic progenitor cells, were purified by a fluorescence-activated cell sorter (FACS) and analyzed for the presence of human immunodeficiency virus-1 (HIV-1) proviral DNA using the polymerase chain reaction. A group of 14 patients with AIDS or AIDS-related complex (ARC) was studied (11 with peripheral blood cytopenias). The CD4+ helper cells in the bone marrow were found positive for HIV-1 DNA in all patients. In contrast, CD34+ progenitor cells were positive in only one patient. Two monocyte samples and two samples of CD4-/CD34- lymphocytes/blasts (mainly B and CD8 lymphocytes) were positive. Proviral DNA could not be detected in granulocytes. FACS analysis showed that the percentage of CD34+ hematopoietic progenitor cells was not altered in the bone marrow of AIDS patients in comparison with the HIV-1 seronegative controls. In contrast, the number of CD4+ lymphocytes was markedly reduced in the bone marrow of AIDS patients. These results show that the hematologic abnormalities in AIDS patients are neither explained by direct infection of the hematopoietic progenitor cells with HIV-1 nor by a depletion of progenitor cells. .A von Laer D; Hufert FT; Fenner TE; Schwander S; Dietrich M; Schmitz H; Kern P. .I 274326 .U 91002878 .S Blood 9101; 76(7):1287-92 .M Adolescence; Adult; Anemia, Aplastic/*DT; Blood Cell Count/DE; Bone Marrow/DE; Drug Evaluation; Female; Hematopoiesis/DE; Human; Injections, Subcutaneous; Interleukin-3/AD/AE/*TU; Male; Middle Age; Recombinant Proteins/AD/AE/TU. .T Effects of recombinant human interleukin-3 in aplastic anemia. .P JOURNAL ARTICLE. .W In a phase I/II study, nine patients with aplastic anemia were treated with recombinant human interleukin-3 (rhIL-3) to assess the toxicity and biologic effects of this multipotential hematopoietic growth factor. Doses ranging from 250 micrograms/m2 to 500 micrograms/m2 were administered as subcutaneous bolus injections daily for 15 days. An increase in platelet counts from 1,000/microL to 31,000/microL was induced by rhIL-3 in one patient, and an increase in reticulocyte counts by more than 10,000/microL in four patients. The blood leukocyte counts temporarily increased in eight patients 1.5- to 3.3-fold (median, 1.8-fold), mainly due to an increase in the number of neutrophils, eosinophils, lymphocytes, and monocytes. In two patients, bone marrow cellularity increased from 7% to 33% and from 10% to 80%, respectively, but without resulting in a substantial improvement of peripheral blood counts. Mild side effects (headache and flushing) were observed in some patients, while low-grade fever occurred in all patients. Transient thrombocytopenia necessitating discontinuation of rhIL-3 treatment occurred in one patient. In conclusion, rhIL-3 can stimulate hematopoiesis in patients with aplastic anemia; however, no lasting effects were obtained. .A Ganser A; Lindemann A; Seipelt G; Ottmann OG; Eder M; Falk S; Herrmann F; Kaltwasser JP; Meusers P; Klausmann M; et al. .I 274327 .U 91002879 .S Blood 9101; 76(7):1293-8 .M Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Combined/AE/TO/*TU; Cyclophosphamide/AD; Etoposide/AD; Human; Injections, Intravenous; Lymphoma, Non-Hodgkin's/*DT/MO/PA; Middle Age; Prednisone/AD; Procarbazine/AD; Remission Induction; Support, U.S. Gov't, P.H.S.. .T CEPP(B): an effective and well-tolerated regimen in poor-risk, aggressive non-Hodgkin's lymphoma. .P JOURNAL ARTICLE. .W Eighty-three patients with intermediate- or high-grade non-Hodgkin's lymphoma were treated with CEPP(B) (cyclophosphamide, etoposide [VP-16], procarbazine, and prednisone with or without bleomycin) chemotherapy at Stanford University Medical Center (Stanford, CA) from January 1982 through June 1989. Sixty-nine received CEPP(B) as second-line or subsequent therapy after relapse from previous combination chemotherapy, and 14 patients received CEPP(B) as first-line therapy. Of 75 patients evaluable for response, 30 patients (40%) achieved a complete response (CR) and 24 patients (32%) achieved a partial response (PR), providing an overall response rate of 72%. Complete responses were recorded on 21 of 61 (34%) patients with recurrent disease and 9 of the 14 patients who received CEPP(B) as first line therapy (64%). Myelosuppression was the major side effect of treatment, resulting in eight neutropenic-febrile episodes from a total of 253 courses. A single fatal toxic event occurred on a patient who developed adult respiratory distress syndrome. Overall, CEPP(B) was well-tolerated and proved to be effective palliative therapy for patients with non-Hodgkin's lymphoma after relapse. As such, CEPP(B) may be considered for cytoreduction before ablative therapy and bone marrow transplantation. CEPP(B) may also be considered for initial therapy in selected patients who cannot tolerate doxorubicin-containing regimens. .A Chao NJ; Rosenberg SA; Horning SJ. .I 274328 .U 91002880 .S Blood 9101; 76(7):1299-307 .M Aged; Aged, 80 and over; Bone Marrow/DE/*PA; Cell Differentiation/DE; Cell Division/DE; Cells, Cultured; Comparative Study; Evaluation Studies; Female; Granulocyte Colony-Stimulating Factor/PD/TU; Granulocyte-Macrophage Colony-Stimulating Factor/PD/TU; Hematopoiesis/*DE; Human; Karyotyping; Male; Middle Age; Myelodysplastic Syndromes/DT/GE/*PA; Recombinant Proteins/PD/TU; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Impact of marrow cytogenetics and morphology on in vitro hematopoiesis in the myelodysplastic syndromes: comparison between recombinant human granulocyte colony-stimulating factor (CSF) and granulocyte-monocyte CSF. .P JOURNAL ARTICLE. .W Marrow cells from 36 patients with myelodysplastic syndromes (MDS) (13 refractory anemia [RA], 14 refractory anemia with excess of blasts [RAEB], 9 RAEB in transformation [RAEB-T]) were evaluated for their in vitro proliferative and differentiative responsiveness to recombinant human granulocyte colony-stimulating factor (G-CSF) or granulocyte-monocyte CSF (GM-CSF). GM-CSF exerted a stronger proliferative stimulus than G-CSF for marrow myeloid clonal growth (CFU-GM) in these patients (44 v 12 colonies per 10(5) nonadherent buoyant bone marrow cells [NAB], respectively, P less than .025). GM-CSF stimulated increased CFU-GM growth in the 16 patients with abnormal marrow cytogenetics in comparison with the 20 patients who had normal cytogenetics (52 and 30 colonies per 10(5) NAB, respectively, P less than .05), whereas no such difference could be demonstrated with G-CSF (11 and 16 colonies per 10(5) NAB, respectively). In contrast, granulocytic differentiation of marrow cells was induced in liquid culture by G-CSF in 15 of 32 (47% patients), while GM-CSF did so in only 4 of 18 (22%) patients (P less than .025) including, for RAEB/RAEB-T patients: 9 of 18 versus 0 of 9, respectively (P less than .025). For MDS patients with normal cytogenetics, G-CSF- and GM-CSF-induced marrow cell granulocytic differentiation in 12 of 18 (67%) versus 3 of 11 (27%), respectively (P less than .025), contrasted with granulocytic induction in only 3 of 14 (21%) and 1 of 7 (14%) patients with abnormal cytogenetics, respectively. We conclude that G-CSF has greater granulocytic differentiative and less proliferative activity for MDS marrow cells than GM-CSF in vitro, particularly for RAEB/RAEB-T patients and those with normal cytogenetics. .A Nagler A; Binet C; Mackichan ML; Negrin R; Bangs C; Donlon T; Greenberg P. .I 274329 .U 91002881 .S Blood 9101; 76(7):1308-14 .M Animal; Bone Marrow/DE/ME/*UL; Cells, Cultured; Fibroblasts/DE/ME/*UL; Gene Expression; Human; Macrophage Colony-Stimulating Factor/*ME/PD; Macrophages/DE/ME/UL; Membrane Proteins/GE/ME/PH; Mice; Mice, Inbred BALB C; Protein Precursors/GE/*ME/PH; Receptor, Macrophage Colony-Stimulating Factor/GE/*ME/PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Direct stimulation of cells expressing receptors for macrophage colony-stimulating factor (CSF-1) by a plasma membrane-bound precursor of human CSF-1. .P JOURNAL ARTICLE. .W Secreted forms of macrophage colony-stimulating factor (M-CSF or CSF-1) are generated by proteolytic cleavage of membrane-bound glycoprotein precursors. Alternatively spliced transcripts of the human CSF-1 gene encode at least two different transmembrane precursors that are differentially processed in mammalian expression systems. The larger precursor rapidly undergoes proteolysis to yield the secreted growth factor and does not give rise to forms of CSF-1 detected on the cell surface. By contrast, the smaller human CSF-1 precursor is stably expressed on the plasma membrane where it is inefficiently cleaved to release a soluble molecule. To determine whether the smaller precursor is biologically active on the cell surface, mouse NIH-3T3 fibroblasts expressing the different forms of human CSF-1 were killed by chemical fixation and tested for their ability to support the proliferation of cells that require this growth factor. Only fixed cells expressing human CSF-1 precursors on their surface stimulated the growth in vitro of a murine macrophage cell line or normal mouse bone marrow-derived mononuclear phagocytes. The ability of these nonviable fibroblasts to induce the proliferation of CSF-1-dependent cells was not mediated by release of soluble growth factor, required direct contact with the target cells, and was blocked by neutralizing antiserum to CSF-1. These results demonstrate that the cell surface form of the human CSF-1 precursor is biologically active and indicate that plasma membrane-bound growth factors can functionally interact with receptor-bearing targets by direct cell-cell contact. .A Stein J; Borzillo GV; Rettenmier CW. .I 274330 .U 91002882 .S Blood 9101; 76(7):1315-22 .M Animal; Bone Marrow/*CY/DE/ME; Cell Differentiation/DE; Cell Division/DE; Cell Line; Cells, Cultured; Granulocyte-Macrophage Colony-Stimulating Factor/*ME; Hematopoiesis/*DE; Hematopoietic Stem Cells/DE; Interleukin-1/PD; Interleukin-6/*ME; Leukemia, Myeloid/ME/*PA; Lipopolysaccharides/PD; Mice; Support, Non-U.S. Gov't; Transcription Factors/ME; Transforming Growth Factor beta/*PD. .T Selective regulation of the activity of different hematopoietic regulatory proteins by transforming growth factor beta 1 in normal and leukemic myeloid cells. .P JOURNAL ARTICLE. .W The viability of normal bone marrow myeloid precursor cells induced by interleukin-6 (IL-6) or IL-1 alpha and the ability of IL-6 and IL-1 alpha to induce the formation of colonies of granulocytes, macrophages, or megakaryocytes in densely seeded bone marrow cultures was suppressed by transforming growth factor-beta 1 (TGF-beta 1). Induction of normal bone marrow colony formation by IL-3 was much less sensitive to TGF-beta 1, and there was little or no effect of TGF-beta 1 on colony formation induced by macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage CSF (GM-CSF). In different clones of myeloid leukemic cells, TGF-beta 1 suppressed differentiation induced with IL-6, IL-1 alpha, or lipopolysaccharide (LPS), but did not suppress differentiation induced with IL-3 or GM-CSF. The effect of TGF-beta 1 on differentiation of the leukemic cells can be dissociated from its effect on cell growth. TGF-beta 1 suppressed the production of IL-6 in normal bone marrow cells cultured with IL-1 alpha and the production of IL-6 and GM-CSF in leukemic cells cultured with IL-1 alpha or LPS. The suppression of IL-6 production can explain the suppression by TGF-beta 1 of the effects of IL-1 alpha and LPS that are mediated by IL-6. TGF-beta 1 also suppressed differentiation in clones of myeloid leukemic cells induced with differentiation factor/leukemia inhibitory factor and tumor necrosis factor. In different leukemic clones TGF-beta 1 suppressed or enhanced induction of differentiation with dexamethasone. The results show that TGF-beta 1 can selectively control the activity of different molecular regulators of normal and leukemic hematopoiesis. .A Lotem J; Sachs L. .I 274331 .U 91002883 .S Blood 9101; 76(7):1323-9 .M Antibodies, Monoclonal/DU/IM; Antibody Affinity/IM; Biological Assay/*MT; Comparative Study; Enzyme-Linked Immunosorbent Assay; Erythropoietin/AN/*BL/IM; Hematologic Diseases/BL; Human; Magnetics; Plasma/*CH; Radioimmunoassay; Spleen/CY; Support, Non-U.S. Gov't. .T A specific in vitro bioassay for measuring erythropoietin levels in human serum and plasma. .P JOURNAL ARTICLE. .W The accurate measurement of biologically active erythropoietin (Ep) in human serum and plasma using present in vivo and in vitro bioassays is difficult because of the presence of both inhibitors and non-Ep stimulators of erythropoiesis. We have developed a simple procedure to quantitatively purify Ep from serum and plasma for subsequent testing in the phenylhydrazine-treated mouse spleen cell assay. The method involves absorption of Ep to an immobilized high-affinity anti-Ep monoclonal antibody and acid elution of the antibody-bound material. After neutralization, the eluted EP is then tested directly in the in vitro bioassay without interference by other serum proteins. By using magnetic beads as a solid support for the antibody, washing and elution steps can be performed rapidly and efficiently. Recoveries of Ep after this procedure show very little sample-to-sample variation and are consistently between 45% and 55%, which is close to the maximum binding expected for the anti-Ep antibody. Coupled with the 7.4-fold concentration that this procedure affords, there is an overall increase in sensitivity of three- to fourfold, which makes this assay suitable for accurately measuring Ep levels in patients with below-average titers. Results with this magnetic bead assay indicate that accurate and reproducible estimates for Ep levels in the serum and plasma from healthy donors as well as from patients with hematologic disorders can be obtained. Titers of biologically active Ep in the sera from a group of patients with either leukemia or lymphoma were found to be elevated, and the values correlated well with titers of immunoreactive Ep measured in the Ep radioimmunoassay. Because of its specificity and high sensitivity, the magnetic bead assay is a valuable alternative to immunoassays for the measurement of elevated, normal, and even subnormal Ep levels in human serum and plasma. .A Wognum AW; Lam V; Goudsmit R; Krystal G. .I 274332 .U 91002884 .S Blood 9101; 76(7):1330-5 .M Animal; Antibodies/IM/PD; Blast Crisis/*PA; Bone Marrow/CY; Cells, Cultured; Cholesterol/AN/PD; Culture Media/AN/PD; Dose-Response Relationship, Drug; Erythrocytes/*CY; Erythroid Progenitor Cells/DE; Erythropoiesis/DE; Erythropoietin/IM/*PD; Female; Hematopoiesis/DE; Hematopoietic Stem Cells/*DE; Lymphocyte Depletion; Megakaryocytes/*CY; Mice; Phosphatidylcholines/AN/PD; Recombinant Proteins/IM/PD; Support, Non-U.S. Gov't. .T Induction of mixed erythroid-megakaryocyte colonies and bipotential blast cell colonies by recombinant human erythropoietin in serum-free culture. .P JOURNAL ARTICLE. .W The effects of recombinant human erythropoietin (rEp) on murine hematopoietic progenitors were studied using a serum-free culture. A high concentration of rEp stimulated the formation of mixed erythroid-megakaryocyte colonies (EM colonies) and blast cell colonies, as well as erythroid colonies, erythroid bursts, and megakaryocyte colonies from normal mouse bone marrow cells. Direct effects of rEp on EM colony, megakaryocyte colony, and erythroid burst formation were confirmed by depletion of accessory cells such as T cells, B cells, and macrophages from crude bone marrow cells, and inhibition of the colonies by the addition of rabbit anti-rEp antibody to the culture in a dose-dependent fashion. Replating experiments were performed to confirm the differentiating ability of blast cell colonies grown in the presence of rEp. Most of the blast cell colonies yielded not only secondary erythroid colonies but also megakaryocyte colonies in the presence of 2 IU/mL rEp. Some of the blast cell colonies produced secondary EM colonies in the presence of 16 IU/ml rEp of 2 IU/mL rEp plus interleukin-3, although no granulocyte-macrophage colonies were found in the secondary culture. These results suggest that Ep acts not only as a late-acting factor that is specific for erythroid progenitors, but also as a bipotential EM-stimulating factor for murine hematopoietic cells. .A Nishi N; Nakahata T; Koike K; Takagi M; Naganuma K; Akabane T. .I 274333 .U 91002885 .S Blood 9101; 76(7):1336-40 .M von Willebrand Factor/*ME/PH; Blood Platelets/CY/*PH; Cell Adhesion/DE/PH; Endothelium, Vascular/CY; Human; Platelet Adhesiveness/DE/PH; Platelet Membrane Glycoproteins/*ME/PH; Support, Non-U.S. Gov't; Uremia/*BL/ME/PP. .T Uremic platelets have a functional defect affecting the interaction of von Willebrand factor with glycoprotein IIb-IIIa. .P JOURNAL ARTICLE. .W Uremic patients have an impaired platelet function that has been related to membrane glycoprotein (GP) abnormalities. Using a perfusion system, we have studied the interaction of normal and uremic platelets with vessel subendothelium (SE) under flow conditions. Reconstituted blood containing washed platelets, purified von Willebrand factor (vWF) (1 U/mL), and normal washed red blood cells was exposed to de-endothelialized rabbit segments for 10 minutes at two different shear rates (800 and 1,600 seconds-1). In some experiments a monoclonal antibody to the GPIIb-IIIa complex (EDU3) was added to the perfusates. With normal platelets, the percentage of the vessel covered by platelets (%CS) was 23.1% +/- 3.7% at 800 seconds-1 and 30% +/- 4.3% at 1,600 seconds-1. Platelets were observed in contact or forming monolayers on vessel SE. EDU3 inhibited the spreading of normal platelets. The %CS (11.1% +/- 3.3%) was statistically decreased (P less than .01) and most of the platelets were observed in contact with the vessel surface. These data indicate that, under flow conditions, the interaction of vWF with GPIIb-IIIa can support the spreading of normal platelets in the absence of exogenous fibrinogen. Under the same experimental conditions, the interaction of uremic platelets with SE was markedly impaired at both shear rates studied (P less than .01 v normal platelets). The presence of EDU3 did not modify the interaction of uremic platelets. These results confirm the impairment of the platelet adhesion observed in uremic patients. Furthermore, they indicate the presence of a functional defect in the interaction of vWF with GPIIb-IIIa. The fact that perfusions with normal and uremic platelets in the presence of an antibody to the GPIIb-IIIa complex did not show any differences gives indirect evidence on a functionally normal interaction vWF/GPIb in uremic patients. .A Escolar G; Cases A; Bastida E; Garrido M; Lopez J; Revert L; Castillo R; Ordinas A. .I 274334 .U 91002887 .S Blood 9101; 76(7):1349-54 .M Cells, Cultured; Human; Interleukin-2/PD; Killer Cells, Lymphokine-Activated/ME/*PA/PH; Leukemia, B-Cell, Chronic/ME/*PA/PP; Leukemia, Hairy Cell/ME/PA/PP; Leukemia, T-Cell, Chronic/ME/*PA/PP; Lymphoproliferative Disorders/ME/PA/PP; Support, Non-U.S. Gov't. .T Lymphokine-activated killer (LAK) cell activity in B and T chronic lymphoid leukemia: defective LAK generation and reduced susceptibility of the leukemic cells to allogeneic and autologous LAK effectors. .P JOURNAL ARTICLE. .W The capacity to generate lymphokine-activated killer (LAK) cells and the susceptibility of the neoplastic cells to both allogeneic and autologous LAK effectors were studied in B and T chronic lymphoproliferative disorders. While in B-cell chronic lymphocytic leukemia (B-CLL) the depressed natural killer function could be restored after a 7-day incubation with recombinant interleukin (IL-2), B-CLL mononuclear cells showed a reduced LAK activity compared with normal LAK cells. Furthermore, in all but 1 of the 20 B-CLL samples tested the leukemic cells were totally resistant to autologous LAK effectors. In most cases the leukemic cells were also resistant to normal allogeneic LAK cells. Competition experiments demonstrated that the patients' LAK cells, as well as normal LAK effectors, were capable of recognizing B-CLL cells, pointing, therefore, to a postbinding cytolytic defect. In hairy cell leukemia (HCL) an overall reduced LAK activity against allogeneic targets was documented, but, at variance from B-CLL, hairy cells were often susceptible to the lytic effect of normal LAK cells, and in half of the cases tested the neoplastic population was also sensitive in an autologous system. Similarly to B-CLL, in the great majority of T chronic lymphoproliferative disorders studied, the pathologic cells were resistant to normal and autologous LAK effectors and a defective LAK generation was found. These results demonstrate that in most B and T chronic leukemias the LAK function is defective and, when inducible, does not appear directed against the leukemic population. The possibility of exploiting an immunotherapeutic approach with IL-2/LAK cells in the management of chronic lymphoproliferative disorders does not gain support by these findings. .A Foa R; Fierro MT; Raspadori D; Bonferroni M; Cardona S; Guarini A; Tos AG; di Celle PF; Cesano A; Matera L. .I 274335 .U 91002888 .S Blood 9101; 76(7):1355-60 .M Antigens, CD/IM; Antigens, Surface/IM; Blood Proteins/PD; Cell Adhesion/DE; Cell Differentiation/DE; Cell Division/DE; Cytotoxicity, Immunologic/IM; Female; Human; Killer Cells, Lymphokine-Activated/IM/*PA/PH; Leukemia, B-Cell, Chronic/BL/*PA/PP; Male; Receptors, Interleukin-2/AN; Stem Cells/PA/PH/UL; Support, Non-U.S. Gov't. .T Distinct characteristics of lymphokine-activated killer (LAK) cells derived from patients with B-cell chronic lymphocytic leukemia (B-CLL). A factor in B-CLL serum promotes natural killer cell-like LAK cell growth. .P JOURNAL ARTICLE. .W We show that lymphokine-activated killer (LAK) cell precursors derived from patients with B-cell chronic lymphocytic leukemia (B-CLL) and cultured in the presence of recombinant interleukin-2 and normal human serum (NHS), develop into primarily NK cell-like (CD 57+) LAK cells, whereas identically prepared LAK cell precursors from normal subjects develop into mainly T cell-like (CD 3+, CD 8+) LAK cells. B-CLL LAK cells exhibited greater proliferative capacity than did normal LAK cells. When normal LAK cells were grown in B-CLL serum instead of NHS, their proliferation increased; NK cell levels also increased to those found in B-CLL LAK cells, suggesting that B-CLL serum contains a factor that promotes NK cell-like growth, LAK cells derived from normal or B-CLL patients demonstrated similar lytic activity toward K562 and Raji cells. Growth in B-CLL serum did not reduce their lytic potential. Thus, the altered phenotype and growth exhibited by B-CLL LAK cells and normal LAK cells grown in B-CLL serum does not lead to abnormalities in their cytolytic functions. We propose instead that the predominance of NK-like cells in B-CLL LAK cell populations and the presence of an NK cell-like growth factor in B-CLL serum reflect abnormalities related to NK cell-mediated B-cell regulation; ie, either inhibition of normal B-cell growth and/or growth stimulation of the leukemic clone in B-CLL. .A Santiago-Schwarz F; Panagiotopoulos C; Sawitsky A; Rai KR. .I 274336 .U 91002889 .S Blood 9101; 76(7):1361-8 .M Antibodies, Monoclonal/*IM; Antigens, Differentiation, T-Lymphocyte/*IM; Cell Line; Cell Transformation, Neoplastic/IM/PA; Cells, Cultured; Human; Leukemia-Lymphoma, T-Cell, Acute, HTLV-I-Associated/IM/*PA; Microscopy, Electron; Neoplasm Circulating Cells/*IM; Phenotype; Sezary Syndrome/IM/*PA; Stem Cells/IM/UL; Support, Non-U.S. Gov't; T-Lymphocyte Subsets/*IM; Tumor Markers, Biological/AN. .T A new monoclonal antibody (CH-F42) recognizes a CD7- subset of normal T lymphocytes and circulating malignant cells in adult T-cell lymphoma-leukemia and Sezary syndrome. .P JOURNAL ARTICLE. .W We describe a new rat immunoglobulin M monoclonal antibody (CH-F42) that recognizes a subset (1.5% to 8%) of normal peripheral blood T lymphocytes. The phenotype of these cells was determined, using dual-color immunofluorescence, to be CD2+, CD3+, CD4+, CD5+, CD7-, CD8-. They do not express T-cell activation markers, and are positive for UCHL1 (CD45RO), but negative for 2H4 (CD45RA). The antigen was expressed on circulating malignant cells in Sezary syndrome (four of four cases) and adult T-cell lymphoma-leukemia (ATLL) (four of six cases) and negative in a variety of other hematologic malignancies tested. These included chronic and acute lymphoid leukemias of B and T lineage, together with chronic and acute myeloid leukemias. However, normal CH-F42+ cells do not display any of the ultrastructural features associated with Sezary or ATLL cells. The marked similarities between these conditions together with the shared expression of an otherwise very restricted surface antigen (CH-F42) provide strong evidence for the existence of a common normal counterpart. Preliminary characterization studies of the antigen, which is also expressed by K562 and Jurkat cells, suggest the CH-F42 antigen is an O-linked, sialated glycan on a glycoprotein. .A Labastide WB; Rana MT; Barker CR. .I 274337 .U 91002890 .S Blood 9101; 76(7):1369-74 .M Acute Disease; Aged; Antigens, Differentiation, T-Lymphocyte/IM; Case Report; Cell Transformation, Neoplastic/DE/PA; Chromosomes, Human, Pair 3/*; Female; Granulocyte-Macrophage Colony-Stimulating Factor/PD; Hematopoiesis/DE; Hematopoietic Stem Cells/DE/PA; Human; Interleukin-3/PD; Interleukin-4/PD; Interleukin-6/PD/PH; Leukemia/GE/IM/*PA; Macrophage Colony-Stimulating Factor/PD; Megakaryocytes/PA; Phenotype; Support, U.S. Gov't, P.H.S.; Translocation (Genetics)/*GE; Tumor Cells, Cultured. .T Characterization of a factor-dependent acute leukemia cell line with translocation (3;3)(q21;q26). .P JOURNAL ARTICLE. .W A strictly factor-dependent cell line (UCSD/AML1) was established from a patient with the syndrome of multilineage acute leukemia with high platelets. The patient's cells and the cell line karyotype were 45,XX,-7,t(3;3)(q21;q26), typical of the syndrome of acute leukemia with high platelets. The cell line expresses CD34, CD7, TdT, and myeloid (CD13, CD14, CD33) and megakaryocyte/platelet (CD36, CD41, CD42b, CDw49b) antigens. In short-term culture, UCSD/AML1 cells proliferate in response to interleukin-3 (IL-3), IL-4, IL-6, macrophage colony-stimulating factor (M-CSF), and granulocyte-macrophage CSF (GM-CSF), but not IL-1, IL-2, IL-5, or G-CSF. In long-term culture, proliferation can be sustained by GM-CSF, IL-6, or M-CSF. When maintained in GM-CSF, a small percentage of cells form multinucleated megakaryocyte-like giant cells. Culture with GM-CSF combined with IL-6, but not with IL-6 alone, increased giant cell formation fourfold to sevenfold. IL-6 alone or in combination with GM-CSF increased expression of platelet-related antigens. In contrast, culture with phorbol ester induced formation of macrophage-like cells. UCSD/AML1 is the first human acute nonlymphocytic leukemia cell line established from a patient with an acute leukemia syndrome associated with a specific chromosome abnormality. .A Oval J; Jones OW; Montoya M; Taetle R. .I 274338 .U 91002892 .S Blood 9101; 76(7):1380-6 .M Cell Division/DE; Cell Line; Cell Membrane/ME/UL; Cell Transformation, Neoplastic/DE/ME; Cobalt Radioisotopes/DU; Cytarabine/PD; Dose-Response Relationship, Drug; Down-Regulation (Physiology)/GE; Gene Expression; Human; Leukemia, Erythroblastic, Acute/ME/*PA; Leukemia, Experimental/ME/*PA; Leukemia, Myeloid/ME/*PA; Receptors, Endogenous Substances/DE/GE/*ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Transcobalamins/ME/PD; Trypsin/PD; Up-Regulation (Physiology)/GE; Vitamin B 12/DU. .T Expression of transcobalamin II receptors by human leukemia K562 and HL-60 cells. .P JOURNAL ARTICLE. .W Plasma membrane receptors for the serum cobalamin-binding protein transcobalamin II (TCII) were identified on human leukemia K562 and HL-60 cells using immunoaffinity-purified human TCII labeled with [57Co]cyanocobalamin. The Bmax values for TCII receptors on proliferating K562 and HL-60 cells were 4,500 and 2,700 per cell, respectively. Corresponding dissociation constants (kd) were 8.0 x 10(-11) mol/L and 9.0 x 10(-11) mol/L. Rabbit TCII also bound to K562 and HL-60 cells but with slightly reduced affinities. Calcium was required for the binding of transcobalamin II to K562 cells. Brief treatment of these cells with trypsin resulted in almost total loss of surface binding activity. After removal of trypsin, surface receptors for TCII slowly reappeared, reaching pretrypsin treatment densities only after 24 hours. Reappearance of receptors was blocked by cycloheximide. TCII receptor densities on K562 and HL-60 cells correlated inversely with the concentration of cobalamin in the culture medium. This suggests that intracellular stores of cobalamin may affect the expression of transcobalamin receptors. Nonproliferating stationary-phase K562 cells had low TCII receptor densities (less than 1,200 receptors/cell). However, the density of TCII receptors increased substantially when cells were subcultured in fresh medium. Up-regulation of receptor expression coincided with increased 3H-thymidine incorporation, which preceded the resumption of cellular proliferation as measured by cell density. In the presence of cytosine arabinoside, which induces erythroid differentiation, K562 cells down-regulated expression of TCII receptors. When HL-60 cells were subcultured in fresh medium containing dimethysulfoxide to induce granulocytic differentiation, the up-regulation of TCII receptors was suppressed. This event occurred well before a diminution of 3H-thymidine incorporation and cessation of proliferation. Thus, changes in the regulation of expression of TCII receptors correlate with both the proliferative and differentiation status of cells. .A Amagasaki T; Green R; Jacobsen DW. .I 274339 .U 91002893 .S Blood 9101; 76(7):1387-91 .M Blotting, Southern; Chromosome Mapping; Chromosomes, Human, Pair 11/CH/UL; DNA, Neoplasm/AN/GE/IM; Gene Rearrangement/GE; Genotype; Human; Lymphoma, Small Cleaved-Cell, Follicular/*GE/UL; Proto-Oncogene Proteins/GE; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Genotypic characterization of centrocytic lymphoma: frequent rearrangement of the chromosome 11 bcl-1 locus. .P JOURNAL ARTICLE. .W Centrocytic lymphomas are defined in the Kiel classification as B-cell lymphomas composed exclusively of cells resembling cleaved follicular center cells (FCC). These lymphomas have been shown to be histologically, immunophenotypically, and clinically distinct from other cleaved FCC lymphomas. DNA from 18 centrocytic lymphomas (14 patients) was analyzed using Southern blotting and probes for immunoglobulin heavy (JH) and kappa light chain (JK) joining gene, T-cell receptor beta chain constant gene (CB), bcl-1, bcl-2, and c-myc gene rearrangements. All of the lymphomas had JH and JK rearrangements, confirming their B-cell origin. None of the specimens had detectable CB, bcl-2, or c-myc rearrangements. However, 4 of 14 patients (28.6%) had rearrangement of the chromosome 11 bcl-1 locus. Therefore, centrocytic lymphomas are genotypically distinguishable from the majority of other small cleaved FCC lymphomas by their lack of demonstrable bcl-2 rearrangements. This supports the distinct nature of centrocytic lymphomas and suggests the lack of importance for the putative oncogene bcl-2 in these cases. Furthermore, the frequent rearrangement of bcl-1 suggests a possible role for this locus in the pathogenesis of at least some centrocytic lymphomas. .A Williams ME; Westermann CD; Swerdlow SH. .I 274340 .U 91002895 .S Blood 9101; 76(7):1398-404 .M Animal; Antibodies/DU/IM; Blotting, Northern; Bone Marrow/CY/DE; Cell Differentiation/DE; Cell Line; Flow Cytometry; Granulocyte Colony-Stimulating Factor/PD; Interleukin-3/PD; Laminin/GE/IM/*ME; Mice; Microscopy, Electron; Neuraminidase/PD; Neutrophils/CY/*ME/UL; Peptide Fragments/GE/*ME; Precipitin Tests; RNA, Messenger/GE/*ME; Stem Cells/CY/DE; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Production of laminin B2 chain protein and messenger RNA by a murine neutrophil precursor cell line, 32Dc13 [see comments] .P JOURNAL ARTICLE. .W Laminin is a heterotrimeric glycoprotein that plays a central role in promoting neutrophil chemotaxis, motility, and attachment to basement membrane. Rabbit peritoneal exudate neutrophils stain positively for laminin, which is presumed to be of exogenous origin and bound to laminin receptors on the cell surface. We examined 32Dc13 cells, a murine neutrophil precursor cell line, by immunoprecipitation. Northern blot analysis, flow cytometry, and electron microscopy for the endogenous production of laminin. Our results demonstrate that 32Dc13 cells endogenously produce a laminin B2 chain protein and messenger RNA (mRNA) without producing any detectable A or B1 chain protein or mRNA. The B2 chain protein was not secreted by the cells; rather it could be detected on the cell surface after treatment of cells with neuraminidase. These findings suggest the possibility of a novel role for the laminin B2 chain in myeloid development and function. .A Tweardy DJ; Sasaki M; Cardamone JJ Jr; McCoy JP Jr; Bonidie MJ; Signorella AP. .I 274341 .U 91002896 .S Blood 9101; 76(7):1405-9 .M Candida albicans/PH; Escherichia coli/ME; Human; Lipopolysaccharides/ME/PD; Neutrophils/*ME; Support, U.S. Gov't, P.H.S.; Time Factors; Transcription, Genetic/GE; Tumor Necrosis Factor/GE/*ME. .T Release of tumor necrosis factor by human polymorphonuclear leukocytes. .P JOURNAL ARTICLE. .W Evidence is presented that human polymorphonuclear neutrophils (PMN) can be induced to produce tumor necrosis factor (TNF). Other investigators have previously reported that TNF has been induced from macrophages by bacteria and, more recently, from natural killer cells by certain tumor cells. Our laboratory has reported that the opportunistic fungi, Candida albicans, can induce TNF, not only from human monocytes, but also from Percoll-fractionated large granular lymphocytes. We now report that incubation of PMN with C albicans for 3 hours was sufficient for detection of TNF release, and peak induction was observed at 8 to 18 hours. This release was inhibitable by actinomycin D, an inhibitor of RNA synthesis, as well as by emetine and cycloheximide, which block protein synthesis. The TNF produced by PMN was neutralized by specific monoclonal antibodies against human TNF. These results represent an important finding that TNF production is a normal response of PMN to stimulation by fungi such as C albicans and suggest that the release of TNF may be related to autocrine activation of PMN effector function to control Candida growth. .A Djeu JY; Serbousek D; Blanchard DK. .I 274342 .U 91002897 .S Blood 9101; 76(7):1410-8 .M Adult; Antibody Formation/*PH; ABO Blood-Group System/IM; Blood Transfusion; Bone Marrow Transplantation/*IM/PA; Centrifugation/MT; Hemagglutinins/AN/ME; Histocompatibility; Human; Isoantibodies/IM; Isoantigens/IM; Lymphocyte Depletion; Reference Standards; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Transplantation, Homologous/IM/PA. .T Reconstitution of antibody response after allogeneic bone marrow transplantation: effect of lymphocyte depletion by counterflow centrifugal elutriation on the expression of hemagglutinins. .P JOURNAL ARTICLE. .W The generation of ABO hemagglutinins was used as a model to assess the tempo of reconstitution of antibody responses in recipients of elutriated (CCE) and nonelutriated (nonCCE) HLA matched bone marrow allografts. The study included 29 CCE recipients (10 major, 6 minor, and 1 major/minor ABO-mismatched, and 12 ABO-matched) and 40 nonCCE recipients (14 major, 12 minor, 2 major/minor, and 12 matched). Plasma volume in the graft and in blood product transfusions was uncorrelated with changes in hemagglutinin titers and therefore was excluded as a significant source of antibody. Removal of graft lymphocytes by CCE did not result in prolongation of host-derived hemagglutinins in recipients of major ABO-mismatched grafts. However, CCE resulted in a complete abrogation of the adoptive transfer of donor-derived antibody as detected in recipients of minor ABO-mismatched grafts. Despite the absence of adoptively transferred donor immunity in recipients of CCE grafts, they had hemagglutinin levels comparable with those of recipients of nonCCE grafts by 6 months after transplantation. This demonstrates that recipients of elutriated marrow were competent to mount de novo responses at that time. The strong correlation between donor pretransplant hemagglutinin titer and recipient titer 1 year after bone marrow transplantation in recipients of nonCCE grafts suggests that even late after transplant, antibody remains the product of adoptively transferred memory cells in recipients of grafts containing large numbers of mature lymphocytes. .A Bar BM; Santos GW; Donnenberg AD. .I 274343 .U 91002898 .S Blood 9101; 76(7):1419-30 .M Animal; Bone Marrow/CY; Bone Marrow Transplantation/IM/*MO/PH; G(M1) Ganglioside/*IM; Graft Survival/*DE/RE; Hematopoiesis/DE/RE; Immune Sera/*IM; Immunization, Passive; Killer Cells, Natural/DE/PH/RE; Lymphocyte Depletion; Male; Mice; Mice, Inbred BALB C; Radiation Chimera; Spleen/CY; Support, Non-U.S. Gov't. .T Anti-asialo GM1 antiserum treatment of lethally irradiated recipients before bone marrow transplantation: evidence that recipient natural killer depletion enhances survival, engraftment, and hematopoietic recovery. .P JOURNAL ARTICLE. .W Natural killer (NK) cells are reported to have an important role in the resistance of lethally irradiated recipients to bone marrow transplantation (BMT). Therefore, we investigated the effects of recipient NK depletion on survival, chimerism, and hematopoietic reconstitution after lethal irradiation and the transplantation of limiting amounts of T-cell-deficient bone marrow (BM). When administered before BMT, anti-asialo GM1 (ASGM1) antiserum treatment, effective in depleting in vivo NK activity, was associated with a marked increase in survival in 3 of 3 allogeneic combinations (BALB/c into C3H/HeN, C57B1/6, or C3B6F1). This enhanced survival was independent of the susceptibility of each recipient strain to accept BALB/c BM. Moreover, recipient anti-ASGM1 treatment was also effective in increasing survival in recipients of syngeneic BM, suggesting that NK cells can adversely affect engraftment independent of genetically controlled polymorphic cell surface determinants. Analysis of chimerism in surviving animals 2 months post-BMT showed that recipient NK depletion significantly increased the level of donor engraftment when high doses of BM were transplanted. These studies also demonstrated that anti-ASGM1 pretreatment mainly resulted in an increase in extramedullary hematopoiesis in the second and third week after irradiation. Anti-ASGM1 treatment also dramatically accelerated the rate of appearance of donor-derived cells with a higher level of donor-cell engraftment apparent at a time when the differences in survival between NK-depleted and control BMT recipients became significant. Peripheral cell counts were also affected by NK depletion, with significantly enhanced platelet and red blood cell recovery and a moderate increase in granulocyte recovery. The overall favorable influence of anti-ASGM1 recipient treatment on hematopoietic events post-BMT suggests that, in humans, pretransplant regimens aimed toward NK depletion should be evaluated. .A Tiberghien P; Longo DL; Wine JW; Alvord WG; Reynolds CW. .I 274344 .U 91002899 .S Blood 9101; 76(7):1431-7 .M Adolescence; Adult; Age Factors; Anemia, Sickle Cell/EP/IM/PP/*SU; Blood Transfusion/*; Child; Child, Preschool; Cross-Sectional Studies; Female; Hemoglobins/GE; Human; Immunity, Cellular/*PH; Immunization/*; Incidence; Isoantibodies/*IM; Isoantigens/*IM; Male; Phenotype; Sex Factors. .T Transfusion and alloimmunization in sickle cell disease. The Cooperative Study of Sickle Cell Disease. .P JOURNAL ARTICLE. .W In 1,814 patients with sickle cell disease who had been transfused, the overall rate of alloimmunization to erythrocyte antigens was 18.6%. The rate of alloimmunization in this group appears to be an explicit function of the number of transfusions received because it increases exponentially with increasing numbers of transfusions. Alloimmunization usually occurred with less than 15 transfusions, although the rate of alloimmunization continued to increase when more transfusions were given. The rate of alloimmunization was less in patients with hemoglobin SC disease and sickle-beta+ thalassemia because these patients had received fewer transfusions. Children less than 10 years old had a slightly lower rate of alloimmunization than patients in other age groups even after correction for the number of transfusions given. Women were more frequently alloimmunized than men; this was largely due to the fact that women received more transfusions than men, but in the age group 16 to 20 years the increase may have been due in part to alloimmunization owing to pregnancy. Forty-five percent of those alloimmunized made antibodies of only one specificity; 17% made four or more antibodies reacting with different antigens. Antibodies to the C and E antigens of the Rh group, the Kell antigen, and the Lewis antigens were most commonly made. These findings may be important in formulating a rational transfusion policy in sickle cell disease. .A Rosse WF; Gallagher D; Kinney TR; Castro O; Dosik H; Moohr J; Wang W; Levy PS. .I 274345 .U 91002900 .S Blood 9101; 76(7):1438-44 .M Agglutinins/IM; Animal; Antibodies/AD/IM; Blood Transfusion/*AE; Disease Models, Animal; Female; Lung/BS/*IN; Male; Neutrophils/IM; Perfusion; Pulmonary Edema/ET; Rabbits; Respiratory Insufficiency/ET; Support, Non-U.S. Gov't; Syndrome. .T Reproduction of transfusion-related acute lung injury in an ex vivo lung model [see comments] .P JOURNAL ARTICLE. .W Leukoagglutinins are implicated in transfusion-related acute lung injury (TRALI). In the present study, severe lung vascular leakage was reproduced by application of a leukoagglutinating antibody of anti-5b specificity in an ex vivo lung model. The antibody originated from a multiparous donor-plasma, observed to cause noncardiogenic edema during transfusion therapy. Heated full plasma (anti-5b-titer 1/128) or purified immunoglobulin G fraction was used for the studies. Ex vivo isolated rabbit lungs were perfused with albumin buffer, and human granulocytes (PMN) were admixed to the recirculating perfusate. In presence of anti-5b antibody plus 5b-positive PMN plus rabbit plasma as complement-source, severe lung edema occurred after a latent period of 3 to 6 hours. Pulmonary artery pressure was only transiently and moderately increased, and the leakage reaction could be traced back to a several-fold increase in lung vascular permeability. In contrast, no vascular leakage was noted in lungs perfused in the absence of anti-5b antibody, PMN, or rabbit plasma. Moreover, no permeability increase occurred on use of 5b-negative PMN. This reproduction of TRALI in an ex vivo lung model corroborates the role of leukoagglutinating antibodies in initiating PMN-dependent respiratory distress and suggests a contribution of concomitant complement activation. .A Seeger W; Schneider U; Kreusler B; von Witzleben E; Walmrath D; Grimminger F; Neppert J. .I 274346 .U 91002901 .S Blood 9101; 76(8):1449-63 .M Child; Chromosome Abnormalities/*; Human; Leukemia, Lymphocytic, Acute/*GE; Neoplasm Recurrence, Local/GE; Philadelphia Chromosome; Ploidies; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Translocation (Genetics); Tumor Cells, Cultured. .T Biology and clinical significance of cytogenetic abnormalities in childhood acute lymphoblastic leukemia. .P JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC. .W Virtually all cases of childhood ALL have chromosomal abnormalities and half contain translocations, which are nearly equally divided between random and nonrandom rearrangements. Nonrandom chromosomal abnormalities have been correlated with leukemic cell lineage, the degree of cell differentiation, and the specific gene involved at the molecular level. Many cytogenetic findings have prognostic significance; however, the adverse influence of certain changes, including most chromosomal translocations, may in fact be offset by the greater cytoreductive effects of intensified therapy. Table 4 summarizes the relation of selected karyotypic findings to treatment outcome in patients treated on contemporary protocols. Among all of the chromosomal abnormalities identified in childhood ALL, hyperdiploidy greater than 50 has been associated with the most favorable prognosis. At the opposite end of the spectrum, the treatment outcome for patients with classical Ph+ or hypodiploid ALL is very poor even in programs of intensive chemotherapy; alternative treatment such as bone marrow transplantation should be considered for such patients. Cases with the t(4;11)(q21;q23) also have a very poor clinical outcome, but the adverse prognosis may be limited to the infant or adolescent age groups. The prognostic significance of other nonrandom translocations, such as t(1;19)(q23;p13) and several other abnormalities, needs to be further assessed in larger numbers of patients. Finally, as more is learned about the molecular pathology underlying these rearrangements, it may be possible to develop new therapeutic agents that are specifically targeted to interfere with the aberrant gene products expressed by human leukemic cells. .A Pui CH; Crist WM; Look AT. .I 274347 .U 91002902 .S Blood 9101; 76(8):1464-72 .M Antibodies, Monoclonal/TU; Antilymphocyte Serum/TU; Bone Marrow Transplantation/*AE; Cyclosporins/TU; Glucocorticoids/TU; Graft vs Host Disease/PC/*TH; Human; Intestinal Diseases/ET/TH; Liver Diseases/ET/TH; Methotrexate/TU; Multivariate Analysis; Retrospective Studies; Skin Diseases/ET/TH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T A retrospective analysis of therapy for acute graft-versus-host disease: initial treatment. .P JOURNAL ARTICLE. .W We have reviewed results of therapy in 740 patients with grades II-IV acute graft-versus-host disease (GVHD) after allogeneic marrow transplantation. At the beginning of therapy, 597 patients (81%) had rash, 369 (50%) had liver dysfunction and 396 (54%) had gut dysfunction. Initial treatment was with glucocorticoids (n = 531), cyclosporine (n = 170), antithymocyte globulin (ATG) (n = 156) or monoclonal antibody (n = 3) either singly (n = 633) or in combination (n = 107). Parameters of GVHD severity in each organ were recorded weekly, and evaluation of response was made using values at the initiation of secondary treatment or, for patients without such treatment, using values on day 29 of primary treatment or the last recorded value before death, whichever occurred first. Minimal criteria for improvement or progression were defined for each organ, but no attempt was made to define liver or gut outcome if another complication such as venocclusive disease or infectious enteritis was present. Improvement rates were 43% for skin disease, 35% for evaluable liver disease and 50% for evaluable gut disease. Overall complete or partial responses were seen in 44% of patients. Multivariate analyses were carried out to identify patient, disease or treatment factors associated with likelihood of overall improvement and likelihood of response in at least one organ. A similar analysis was also carried out to identify covariates associated with time to treatment failure (defined as initiation of secondary therapy or death not due to relapse of malignancy). In all three models, GVHD prophylaxis using cyclosporine combined with methotrexate was associated with favorable GVHD treatment outcome compared to prophylaxis with either agent alone, and treatment with glucocorticoids or cyclosporine was more successful than treatment with ATG. Other factors associated with unfavorable outcome in the model of time to treatment failure and also entered in one of the response models were recipient HLA disparity with the donor, presence of a liver complication other than GVHD, and early onset of GVHD. Results of this analysis indicate that glucocorticoids represent the best initial therapy available for treatment of acute GVHD, although much room for improvement remains. .A Martin PJ; Schoch G; Fisher L; Byers V; Anasetti C; Appelbaum FR; Beatty PG; Doney K; McDonald GB; Sanders JE; et al. .I 274348 .U 91002903 .S Blood 9101; 76(8):1473-80 .M Animal; Bone Marrow; Dose-Response Relationship, Drug; Granulocyte-Macrophage Colony-Stimulating Factor/AD/*PD; Hematopoiesis/*; Hematopoietic Stem Cells/CY; Leukocyte Count; Male; Megakaryocytes/*CY; Mice; Mice, Inbred CBA; Platelet Count; Recombinant Proteins; Spleen/CY; Support, Non-U.S. Gov't. .T In vivo stimulation of megakaryocytopoiesis by recombinant murine granulocyte-macrophage colony-stimulating factor. .P JOURNAL ARTICLE. .W Murine recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) was injected in mice, and the effects on bone marrow, splenic megakaryocytes, megakaryocyte precursors (megakaryocyte colony-forming units [CFU-Meg]) were evaluated. In mice injected three times a day for 6 days with 12,000 to 120,000 U rGM-CSF, no significant modification of both platelet levels and mean platelet volume was observed, while there was a twofold increase in blood neutrophils. However, the rate of platelet production, as assessed by the measurement of 75selenomethionine incorporation into blood platelets, was On the contrary, administration of up to 384,000 U rGM-CSF two times a day for 2 days, as for a typical "thrombopoietin assay," failed to modify platelet production. A significant dose-related increase in the number of splenic megakaryocytes occurred in mice receiving 60,000 to 120,000 U rGM-CSF, while a slight increase in the number of bone marrow megakaryocytes was observed in mice injected with 120,000 U rGM-CSF. The proportion of bone marrow megakaryocytes with a size less than 18 microns and greater than 35 microns resulted significantly higher in mice receiving rGM-CSF in comparison with controls; an increase in the percentage of splenic megakaryocytes greater than 35 microns was also observed. A statistically significant increase in the total spleen content of CFU-Meg was observed after administration of 90,000 and 120,000 U rGM-CSF three times a day for 6 days, while no effect on bone marrow CFU-Meg was recorded, irrespective of the dose delivered. Finally, 24 hours after a single intravenous injection of rGM-CSF, there was a significant increase in the proportion of CFU-Meg in S-phase, with the splenic progenitors being more sensitive than bone marrow-derived CFU-Meg. These data indicate that rGM-CSF has in vivo megakaryocyte stimulatory activity, and are consistent with previous in vitro observations. However, an effective stimulation of megakaryocytopoiesis in vivo, bringing about an increase in the levels of blood platelets, may require interaction of rGM-CSF with other cytokines. .A Vannucchi AM; Grossi A; Rafanelli D; Ferrini PR. .I 274349 .U 91002904 .S Blood 9101; 76(8):1481-9 .M Antibodies/PD; Enzyme-Linked Immunosorbent Assay; Granulocyte-Macrophage Colony-Stimulating Factor/*BL/GE/IM; Human; Interleukin-1/BL/PD/*PH; Leukemia, Myelocytic, Acute/*BL/PA; RNA, Messenger/ME; Support, Non-U.S. Gov't; Tumor Cells, Cultured. .T Coordinate secretion of interleukin-1 beta and granulocyte-macrophage colony-stimulating factor by the blast cells of acute myeloblastic leukemia: role of interleukin-1 as an endogenous inducer. .P JOURNAL ARTICLE. .W Acute myeloblastic leukemia (AML) blasts have been shown to produce a variety of cytokines in culture such as interleukin-1 (IL-1), IL-6, granulocyte-, macrophage-, and granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF alpha). Using two sensitive and specific enzyme-linked immunosorbent assays for IL-1 beta and GM-CSF, we document in the present study that the production of the two cytokines by AML blasts in culture is coordinated. First, we observe a striking correlation between the levels of GM-CSF and IL-1 beta released by the cells. Thus, a high production of IL-1 beta is always concordant with a high production of GM-CSF and, conversely, low production of IL-1 beta is concordant with low levels of GM-CSF. Second, neutralization of intrinsic IL-1 using antibodies that are specific for IL-1 alpha and -1 beta suppresses the release of GM-CSF by the cells. Third, neutralization of the endogenous source of IL-1 also results in an abrogation of GM-CSF mRNA. Fourth, the production of both IL-1 beta and GM-CSF is up-regulated by exposing AML blasts to an exogenous source of IL-1, suggesting a positive regulation of autocrine growth factor production. Taken together, our results indicate that GM-CSF production by AML blasts is mediated by endogenously produced IL-1. Both IL-1 beta and -1 alpha are produced by AML blasts, although IL-1 beta appears to be more abundant. Spontaneous colony formation by AML blasts is abrogated by the addition of neutralizing antibodies against IL-1 beta and GM-CSF, whereas each antibody alone has little effect on blast proliferation. Taken together, our results are consistent with the view that the production of IL-1 beta by AML blasts supports autocrine growth in culture, through induction of CSFs or other cytokines that stimulate blast proliferation. .A Rodriguez-Cimadevilla JC; Beauchemin V; Villeneuve L; Letendre F; Shaw A; Hoang T. .I 274350 .U 91002905 .S Blood 9101; 76(8):1490-3 .M Cell Division; Cells, Cultured; Human; HIV/DE/*PH; Interleukin-3/*PD; Monocytes/*CY/MI; Support, Non-U.S. Gov't; Virus Replication/DE; Zidovudine/*PD. .T Induction of monocyte proliferation and HIV expression by IL-3 does not interfere with anti-viral activity of zidovudine. .P JOURNAL ARTICLE. .W Myelosuppression is a major symptom in the acquired immunodeficiency syndrome (AIDS). Moreover zidovudine, an anti-retroviral drug used to treat AIDS patients has myelosuppressive side effects. Therefore treatment with IL-3, a multi-lineage hemopoietic growth factor may be beneficial for zidovudine-treated individuals. In this study we examined the effect of IL-3 on human immunodeficiency virus (HIV) expression. The proliferative response to rIL-3 and the effects on the replication of the monocytotropic HIV variant, HTLV-III Ba-L, in the absence or presence of the anti-retroviral drug zidovudine was studied in purified human peripheral blood monocytes. Zidovudine concentrations sufficient for complete inhibition of HIV replication did not affect rIL-3 induced monocyte proliferation. Although rIL-3, like rGM-CSF, was able to augment HIV expression in monocytes, it did not interfere with the anti-retroviral activity of zidovudine. These data indicate that rIL-3 is a potential candidate for use in myelosupportive therapy in AIDS patients treated with anti-retroviral drugs. .A Schuitemaker H; Kootstra NA; van Oers MH; van Lambalgen R; Tersmette M; Miedema F. .I 274351 .U 91002906 .S Blood 9101; 76(8):1494-502 .M Adult; Aged; Bone Marrow/CY; Bone Marrow Diseases/DT/PA; Cell Division; DNA/BI; Erythroid Progenitor Cells/CY; Female; Granulocytes/CY; Hematopoiesis; Hematopoietic Stem Cells/*CY/ME; Human; Interleukin-3/*PD/TU; Leukocyte Count; Macrophages/CY; Male; Middle Age; Neoplasms/DT/PA; Recombinant Proteins/PD. .T Effects of recombinant human interleukin-3 on human hematopoietic progenitor and precursor cells in vivo. .P CLINICAL TRIAL; JOURNAL ARTICLE. .W DNA-synthesis rates and concentrations of bone marrow (BM) and peripheral blood (PB) progenitor cells were studied in 22 patients treated with recombinant human interleukin-3 (rhIL3) as part of a clinical phase I/II study. Recombinant hIL3 at doses of 60 to 500 micrograms/m2 was administered by subcutaneous bolus injection for 15 days to 13 patients with solid tumors and preserved hematopoietic function and to nine patients with bone marrow failure, including five with myelodysplastic syndromes. Following treatment with rhIL3, the percentage of actively cycling BM erythroid (BFU-E) and multilineage (CFU-GEMM) progenitors in patients with preserved hematopoietic function increased from 16% to 36% (P less than .05) and from 10% to 40% (P less than .01), respectively. The DNA-synthesis rates of early and late granulocyte macrophage progenitor cells increased from 11% to 26% (CFU-GM day 14; P less than .02) and from 13% to 30% (CFU-GM day 7; P less than .05). There was an increase in BM cellularity from 37% to 58%, and of the myeloid to erythroid ratio from 1.4 to 3.2, while the concentration of marrow progenitors on a per cell basis was unchanged or slightly decreased. The frequencies of blast cells in the BM were unchanged. Mean levels of PB CFU-GM day 14 and CFU-GEMM were 100% and 72% above baseline values after 7 days of rhIL3 but only 25% and 28% above initial levels at the end of treatment. Peripheral blood BFU-E were reduced in the majority of patients with normal marrow after both 7 and 15 days of rhIL3. No augmentation of circulating BFU-E and CFU-GEMM was seen in 5 patients with MDS who had few or no PB BFU-E or CFU-GEMM initially. Total leukocyte, neutrophil, and eosinophil counts increased significantly (P less than .01) in 21 of 22 patients with a peak response after a median of 13 days of rhIL3. While a small increase in reticulocytes was not accompanied by an elevation of the hemoglobin or hematocrit, platelet counts increased by 50% in patients with preserved marrow function. Thus, rhIL3 induces a multilineage response in vivo, apparently by stimulating proliferation of multipotential and lineage-restricted progenitors. It remains to be determined whether this is due to direct or indirect effects on the progenitor cells. .A Ottmann OG; Ganser A; Seipelt G; Eder M; Schulz G; Hoelzer D. .I 274352 .U 91002907 .S Blood 9101; 76(8):1503-13 .M Adenosine Diphosphate/PD; Blood Platelets/DE/*ME; Calcimycin/PD; Cell Membrane/DE/ME; Fixatives; Flow Cytometry; Fluorescent Antibody Technique; Formaldehyde; Human; Immunohistochemistry; Macromolecular Systems; Microscopy, Electron; Microscopy, Electron, Scanning; Platelet Membrane Glycoproteins/*ME; Polyethylene Glycols; Polymers; Support, Non-U.S. Gov't; Thrombin/*PD. .T Thrombin induces a rapid redistribution of glycoprotein Ib-IX complexes within the membrane systems of activated human platelets. .P JOURNAL ARTICLE. .W Previous studies have shown a decreased binding of monoclonal antibodies (MoAbs) to glycoprotein (GP) Ib-IX complexes on thrombin-stimulated platelets, but the reason for this is poorly understood. We have used (1) immunofluorescence procedures and flow cytometry, and (2) immunogold staining and electron microscopy to investigate this phenomenon. Washed platelets were incubated with alpha-thrombin, adenosine diphosphate, or ionophore A23187 for increasing lengths of time. For alpha-thrombin, but not the other agonists, flow cytometry confirmed a dose- and time-dependent decrease in the binding of MoAbs specific for GP Ib alpha (AP-1, Bx-1), GP IX (FMC 25), or to the complex itself (SZ 1). Immunoglold staining performed using standard transmission or scanning electron microscopy high-lighted surface areas devoid of bound antibody. However, a quantitatively normal immunofluorescence was restored if paraformaldehyde-fixed, thrombin-stimulated platelets were permeabilized with Triton X-100 (Sigma Chemical Co, St Louis, MO) before MoAb addition, while immunogold staining was now seen to be concentrated within the interior of the platelet. Glutaraldehyde-fixed samples were then embedded in the resin Lowicryl K4M (Taab Laboratories Equipment Ltd, Aldermaston, England) and immunogold staining performed on thin sections using a polyclonal antibody to glycocalicin. An increased presence of GP Ib-IX complexes within surface-connected membrane systems of the thrombin-stimulated platelets was confirmed. Interestingly, GP Ib-IX movement was opposite to the thrombin-induced externalization of internal pools of GP IIb-IIIa complexes and of the alpha-granule membrane GP, GMP-140. .A Hourdille P; Heilmann E; Combrie R; Winckler J; Clemetson KJ; Nurden AT. .I 274353 .U 91002908 .S Blood 9101; 76(8):1514-20 .M Animal; Fibrosarcoma/ME; Glycosylation; Guanidines/PD; Half-Life; Human; Metabolic Clearance Rate; Plasminogen Inactivators/BL/*PK; Rabbits; Tissue Distribution; Tumor Cells, Cultured. .T The pharmacokinetics of plasminogen activator inhibitor-1 in the rabbit. .P JOURNAL ARTICLE. .W The pharmacokinetics of the activated and latent forms of plasminogen activator inhibitor-1 (PAI-1) isolated from HT1080 fibrosarcoma cells (HT1080 PAI-1) and a nonglycosylated form of human PAI-1 isolated from a yeast expression system (rPAI-1) were followed in the rabbit. As assessed by an immunologic assay specific for human PAI-1, guanidine HCI activated HT1080 PAI-1 and rPAI-1 entered the total plasma volume following intravenous bolus administration and exhibited a biphasic clearance pattern. The t1/2s of HT1080 PAI-1 for the initial and beta phases equalled 6.0 and 24.8 minutes, respectively. The t1/2s of rPAI-1 for the initial and beta phases equalled 8.8 and 34.0 minutes, respectively. Similar results were obtained by measuring PAI-1 activity in plasma and with trace amounts of 125I-rPAI-1, suggesting that the above pharmacokinetic behavior could also apply to endogenous PAI-1. The liver was the main site of rPAI-1 clearance. Unactivated, latent PAI-1 exhibited a very different pharmacokinetic profile. Over 80% of latent rPAI-1 cleared from the circulation within 10 minutes (t1/2 = 1.7 minutes). The difference in clearance behavior between activated and latent PAI-1 may be related to the ability of activated PAI-1, but not latent PAI-1, to rapidly form high-molecular-weight complexes with plasma binding factors which were observed in vitro and in vivo. Because PAI-1 could potentially tilt the fibrinolytic balance toward a prothrombotic state, its rapid clearance may represent an important control mechanism governing the circulating levels of this key component of the fibrinolytic pathway. .A Mayer EJ; Fujita T; Gardell SJ; Shebuski RJ; Reilly CF. .I 274354 .U 91002909 .S Blood 9101; 76(8):1521-9 .M Animal; Antithrombin III/*GE/ME; Cell-Free System; Chromatography; Cloning, Molecular; DNA/GE; Electrophoresis, Polyacrylamide Gel; Gene Expression/*; Heparin/*ME; Human; Immunosorbent Techniques; Molecular Weight; Mutagenesis, Site-Directed; Rabbits; RNA, Messenger/GE; Signal Peptides/GE; Support, Non-U.S. Gov't; Thrombin/*ME; Translation, Genetic. .T Expression in a cell-free system of normal and variant forms of human antithrombin III. Ability to bind heparin and react with alpha-thrombin. .P JOURNAL ARTICLE. .W Human antithrombin III (AT-III) cDNA was cloned into the cell-free expression phagemid vector pGEM-3Zf(+) and site-directed mutagenesis was used to remove nucleotides encoding the signal peptide. AT-III messenger RNA (mRNA) transcripts derived from this construct were translated in an mRNA-dependent rabbit reticulocyte lysate (RRL) system containing (35S)methionine. Immunoprecipitation of the cell-free translation mixture with rabbit polyclonal antibodies to AT-III showed, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), a 47-Kd polypeptide which is the non-glycosylated mature form of plasma AT-III. Densitometric scanning showed that this polypeptide constitutes greater than 90% of the radiolabeled polypeptides produced in this system. Heparin-Sepharose chromatography resulted in the elution of cell-free derived AT-III as a broad peak between 0.2 and 0.7 mol/L NaCl. The cell-free derived AT-III also reacted with human alpha-thrombin. In 2 minutes approximately 20% of the AT-III was found associated with a higher molecular weight species, consistent with the formation of a 1:1 stoichiometric covalent complex between alpha-thrombin and AT-III. Unfractionated heparin accelerated the rate of formation of such complexes. When Ser394 was mutated to Leu to form the AT-III Denver mutant, the cell-free translation product of this mutation did not show any significant complex formation when reacted with alpha-thrombin. A truncated form of AT-III (Met251-Lys432), containing only the putative thrombin-binding domain, was synthesized independently. This 21-Kd polypeptide did not bind heparin; however, it was cleaved by alpha-thrombin presumably at the reactive center Arg393-Ser394. When Ser394 was mutated to Leu the cell-free translation product of this truncated AT-III mutation did not react with alpha-thrombin at the reactive center. This simple cell-free approach, along with site-directed mutagenesis, should allow for the rapid and accurate mapping of the functional domains of human AT-III. .A Austin RC; Rachubinski RA; Fernandez-Rachubinski F; Blajchman MA. .I 274355 .U 91002910 .S Blood 9101; 76(8):1530-7 .M Alanine/*; Amino Acid Sequence; Base Sequence; Deoxyribonucleases, Type II Site-Specific/ME; DNA/GE/ME; DNA Restriction Enzymes/ME; Epidermal Growth Factor-Urogastrone/*; Exons; Factor IX/CH/*GE/PD; Factor IXa/ME; Genetic Markers; Hemophilia/*BL; Human; Molecular Sequence Data; Mutation/*; Partial Thromboplastin Time; Polymerase Chain Reaction; Proline/*; Promoter Regions (Genetics); Protein Conformation; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Factor IXHollywood: substitution of Pro55 by Ala in the first epidermal growth factor-like domain. .P JOURNAL ARTICLE. .W Factor IX is a multidomain protein essential for hemostasis. We describe a mutation in a patient affecting the first epidermal growth factor (EGF)-like domain of the protein. All exons and the promoter region of the gene were amplified by the polymerase chain reaction method, and sequenced. Only a single mutation (C----G), that predicts the substitution of Pro55 by Ala in the first EGF domain was found in the patient's gene. This mutation leads to new restriction sites for four enzymes. One new site (Nsi) was tested in the amplified exon IV fragment and was shown to provide a rapid and reliable marker for carrier detection and prenatal diagnosis in the affected family. The factor IX protein, termed factor IXHollywood (IXHW), was isolated to homogeneity from the patient's plasma. As compared with normal factor IX (IXN), IXHW contained the same amount of gamma-carboxy glutamic acid but twice the amount of beta-OH aspartic acid. Both IXHW and IXN contained no detectable free -SH groups. Further, IXHW could be readily cleaved to yield a factor IXa-like molecule by factor Xla/Ca2+. However, IXaHW (compared with IXaN) activated factor X approximately twofold slower in the presence of Ca2+ and phospholipid (PL), and 8- to 12-fold slower in the presence of Ca2+, PL, and factor VIIIa. Additionally, IXaHW had only approximately 10% of the activity of IXaN in an aPTT assay. In agreement with the nuclear magnetic resonance-derived structure of EGF, the Chou-Fasman algorithm strongly predicted a beta turn involving residues Asn-Pro55-Cys-Leu in IXN. Replacement of Pro55 by Ala gave a fourfold decrease in the beta turn probability for this peptide, suggesting a change(s) in the secondary structure in the EGF domain of IXHW. Since this domain of IXN is thought to have one high-affinity Ca2+ binding site and may be involved in PL and/or factor VIIIa binding, the localized secondary structural changes in IXHW could lead to distortion of the binding site(s) for the cofactor(s) and, thus, a dysfunctional molecule. .A Spitzer SG; Kuppuswamy MN; Saini R; Kasper CK; Birktoft JJ; Bajaj SP. .I 274356 .U 91002911 .S Blood 9101; 76(8):1538-45 .M Animal; Blood Coagulation/DE; Blood Coagulation Disorders/CI/*PC; Comparative Study; Factor VII/*AI/TU; Fibrinogen/ME; Human; Lipoproteins/*TU; Partial Thromboplastin Time; Protease Inhibitors/*TU; Prothrombin Time; Rabbits; Recombinant Proteins/TU; Thromboplastin/*/*AI/PD/TU. .T Recombinant lipoprotein-associated coagulation inhibitor inhibits tissue thromboplastin-induced intravascular coagulation in the rabbit. .P JOURNAL ARTICLE. .W Lipoprotein-associated coagulation inhibitor produces feed-back inhibition of tissue factor (tissue thromboplastin)-induced coagulation in the presence of factor Xa Recombinant lipoprotein-associated coagulation inhibitor (rLACI) was tested for its ability to modify thromboplastin-induced intravascular coagulation in a rabbit model that allows monitoring of iodine-125 fibrin accumulation/disappearance in the lung and sampling of blood for the measurement of coagulation parameters. Infusion of thromboplastin into the rabbit caused a rapid increase of radioactivity over the lungs, possibly due to the accumulation of 125I fibrin in the lungs, followed by a rapid decline of radioactivity, suggestive of removal of fibrin from the lungs. Thromboplastin also caused a rapid decrease of systemic fibrinogen that was accompanied by a lengthening of the activated partial thromboplastin time and prothrombin time. The effect of coinfusion of rLACI with thromboplastin or bolus injection of rLACI before thromboplastin infusion was studied. At a high dose of rLACI (800 micrograms/kg body weight), the thromboplastin-induced radioactivity increase in the lungs and the systemic fibrinogen decrease were completely suppressed. The activated partial thromboplastin time and prothrombin time of the plasma samples lengthened, possibly due to the presence of thromboplastin in circulation. The thromboplastin-induced radioactivity increase over the lungs was not completely suppressed by lower doses of rLACI (135 to 270 micrograms/kg body weight), but these doses of rLACI prevented systemic fibrinogen decrease. At a bolus dose of 23 micrograms/kg body weight, rLACI provided 50% protection of the fibrinogen consumption (fibrinogen decreased to 82% compared with 65% in rabbits treated with thromboplastin alone). These results show that rLACI is effective in the inhibition of thromboplastin-induced coagulation in vivo. .A Day KC; Hoffman LC; Palmier MO; Kretzmer KK; Huang MD; Pyla EY; Spokas E; Broze GJ Jr; Warren TG; Wun TC. .I 274357 .U 91002914 .S Blood 9101; 76(8):1564-71 .M Adenosine Diphosphate/PD; Antibodies, Monoclonal/*PD; Blood Platelets/DE/*PH/UL; Cytoskeleton/ME; Human; Immunohistochemistry; Microscopy, Electron; Microscopy, Electron, Scanning; Platelet Aggregation/DE/*PH; Platelet Membrane Glycoproteins/IM/*PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Thrombin/PD. .T Monoclonal antibodies bound to subunits of the integrin GPIIb-IIIa are internalized and interfere with filopodia formation and platelet aggregation. .P JOURNAL ARTICLE. .W The monoclonal antibodies Tab and AP3 are directed, respectively, against GPIIb and GPIIIa, the subunits of the platelet fibrinogen receptor. When added together to platelets, these antibodies prevent adenosine diphosphate (ADP)-induced platelet aggregation, despite normal fibrinogen binding (Newman et al, Blood 69:668, 1987). To explore the cellular requirements of aggregation after fibrinogen binding, we used several techniques to study platelets treated with Tab and AP3, then stimulated with ADP. We used scanning and transmission electron microscopy to evaluate platelet morphology, immunolabel-surface replication to determine whether individual GPIIb-IIIa complexes clustered, immunocytochemistry on frozen thin sections to study the subcellular distribution of the integrin GPIIb-IIIa and fibrinogen, and biochemical methods to assess the activation of the platelet cytoskeleton. We found that the treated cells had short, blunted projections instead of normal filopodia. Other morphologic abnormalities, apparent in thin section, were aberrantly placed alpha-granules and microtubules, and a prominent, worm-like, fibrinogen-filled surface-connected canalicular system. Biochemical analysis suggested that such platelets undergo massive actomyosin-controlled membrane flow, which serves to sequester GPIIb-IIIa and makes the platelets refractory to aggregation. We conclude that aggregation requires the formation of long, slender filopodia, probably directed by cytoskeletal rearrangements after activation, and that the transmembrane GPIIb-IIIa complex may play a role in signaling these events. .A Isenberg WM; Bainton DF; Newman PJ. .I 274358 .U 91002916 .S Blood 9101; 76(8):1580-5 .M Adolescence; Adult; Aged; Anemia, Aplastic/BL/*DT; Antigens, CD/AN; Antigens, Differentiation/AN; B-Lymphocyte Subsets/IM/PA; Cell Division; Granulocyte-Macrophage Colony-Stimulating Factor/*TU; Human; HLA-DR Antigens/AN; Killer Cells, Natural/IM; Leukocyte Count; Lymphocyte Subsets/IM/PA; Lymphocyte Transformation; Middle Age; Receptors, Transferrin/AN; Recombinant Proteins/TU; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; T-Lymphocyte Subsets/IM/PA. .T Effect of recombinant human granulocyte-macrophage colony-stimulating factor administration on the lymphocyte subsets of patients with refractory aplastic anemia. .P JOURNAL ARTICLE. .W Human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was administered to 14 patients with refractory aplastic anemia (AA). The effect of rhGM-CSF therapy on the lymphocyte phenotype; on the proliferative responses to the mitogen phytohemagglutinin, Candida albicans, and tetanus toxoid antigens; and on the natural killer (NK) activity of the circulating lymphocytes was studied. Samples were collected before (baseline) and twice during the rhGM-CSF administration. The absolute number of circulating lymphocytes remained relatively constant during the first period, but experienced a significant increase (P less than .001) during the second period. The increase was most prominent in the B cells (P less than .001), but the T cells (P less than .016) also increased. Detailed investigation of lymphocyte subsets showed an increase of the markers CD38 (Leu17), HLA-DR, and the transferrin receptor throughout the treatment course giving evidence of lymphoid cell activation. The NK cell activity was suppressed (P less than .008) throughout the treatment. However, proliferative responses to phytohemagglutinin, Candida antigen, and tetanus toxoid were unaffected. Although the mechanism is not yet defined, GM-CSF does induce activation and increase in absolute lymphoid cell number, especially B cells, together with a decrease in NK cytotoxicity. The implication of these immune cell changes in relation to host resistance to microorganisms remains to be established. .A Faisal M; Cumberland W; Champlin R; Fahey JL. .I 274359 .U 91002921 .S Blood 9101; 76(8):1614-21 .M Acute Disease; Adult; Aged; Female; Gene Rearrangement, T-Lymphocyte; Histocytochemistry; Human; Immunophenotyping; Leukemia/DT/*GE/PA; Leukemia, Lymphocytic, Acute/GE/PA; Leukemia, Myelocytic, Acute/GE/PA; Male; Middle Age; Prognosis; Stains and Staining; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Trisomy/*. .T Trisomy 13: a new recurring chromosome abnormality in acute leukemia. .P JOURNAL ARTICLE. .W A new recurring chromosome abnormality was identified in 8 of 621 consecutive successfully karyotyped adults with de novo acute leukemia. These eight patients had trisomy 13 as the sole cytogenetic abnormality. On central morphologic review, five cases were classified as subtypes of acute myeloid leukemia, one as acute mixed lymphoid and myeloid leukemia, one as acute lymphoid leukemia, and one as acute undifferentiated leukemia. Blasts of all eight cases expressed one or more myeloid differentiation antigens. Three also expressed T-lineage-associated antigens; however, none of these had rearrangement of the T-cell receptor beta, gamma, or delta genes. Four of six cases tested were TdT positive. All eight patients with trisomy 13 were treated with intensive induction chemotherapy; only three entered a short-lived complete remission. Survival of patients with trisomy 13 ranged from 0.5 to 14.7 months, and was significantly shorter than that of the remaining patients (median 9.5 v 16.2 months, P = .007). We conclude that trisomy 13 is a rare, recurring clonal chromosome abnormality in acute leukemia associated with a poor prognosis. Malignant transformation of an immature hematopoietic precursor cell is suggested by the expression of antigens characteristic of both the myeloid and lymphoid lineage, the high incidence of TdT positivity, and the morphologic heterogeneity in these leukemias. .A Dohner H; Arthur DC; Ball ED; Sobol RE; Davey FR; Lawrence D; Gordon L; Patil SR; Surana RB; Testa JR; et al. .I 274360 .U 91002922 .S Blood 9101; 76(8):1622-5 .M Benzimidazoles/ME; Cell Fractionation; Cell Nucleus/ME/*UL; Chromomycins/ME; Comparative Study; DNA/ME; Fixatives; Fluorescent Dyes/ME; Histological Techniques/*; Human; Lymphocytes/UL; Methacrylates/*; Propidium; Stains and Staining; Support, U.S. Gov't, P.H.S.; Tonsil/UL. .T Recovery of nuclei from glycol-methacrylate-embedded tissue. .P JOURNAL ARTICLE. .W The analysis of antigens, enzyme histochemical markers, and DNA has become an important part of the classification of some leukemias, lymphomas, and other neoplastic diseases. Many of the relevant antigens and most of the relevant enzyme histochemical activities are destroyed and others are less than optimally preserved in tissues embedded in hot paraffin. Most enzymatic activities and antigens are well preserved in tissues embedded at 4 degrees C in glycol methacrylate (GMA). The measurement of DNA content in neoplastic cells with the most commonly employed techniques depended on the availability of fresh suspensions of cells until the development by Hedley of methods that permit the recovery of nuclei from paraffin blocks for this purpose. In order to facilitate the analysis of antigens, enzymatic markers, and DNA from the same sample of tissue, we have developed a means of recovery of nuclei from GMA-embedded tissues. Twenty-microns-thick sections of GMA-embedded tonsil were either pretreated with an organic solvent (absolute ethanol or 2-ethoxyethanol) followed by rehydration in phosphate buffered saline (PBS) or directly rehydrated in PBS. The suspensions were formed mechanically by gentle sonication. The type of fixative and length of PBS rehydration were varied. Tissue fixed in 100% acetone, embedded in GMA, and rehydrated directly in PBS for six days gave the highest average yield of nuclei, 3.7 x 10(7) nuclei per gram tissue. In order to assess DNA binding of fluorescent dyes, 2-microns-thick GMA sections were stained with chromomycin, Hoechst 33342 (Sigma Chemical, St Louis, MO), and propidium iodide. Hoechst 33342 bound specifically to the nuclei with low background staining. .A Wright ET; Jacobberger JW; Pretlow TP; Pretlow TG. .I 274361 .U 91002923 .S Blood 9101; 76(8):1626-30 .M Child; Chromosome Abnormalities/*; Chromosome Banding; Chromosome Deletion; Chromosomes, Human, Pair 6/*; Genotype; Human; Immunophenotyping; Leukemia, Lymphocytic, Acute/*GE; Ploidies; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Translocation (Genetics). .T Abnormalities of the long arm of chromosome 6 in childhood acute lymphoblastic leukemia. .P JOURNAL ARTICLE. .W To determine the biologic significance of the structural rearrangements of the long arm of chromosome 6(6q) in acute lymphoblastic leukemia (ALL) at diagnosis, we studied 412 consecutive children whose leukemic cell chromosomes had been completely banded and identified 45 (11%) children with this abnormality. The 45 cases were divided into del(6q) only (n = 11), del(6q) and numerical abnormalities (n = 4), del(6q) and structural abnormalities (n = 23), and 6q translocations (n = 7). The breakpoints of del(6q) were subgrouped: del(6)(q15q21) in 11 cases, del(6) (q13q21) in six, del(6)(q21q23) in four, del(6)(q15) in four, del(6)(q15q23) in three, and other deletions in 10 cases. Notably, all these deletions encompassed the 6q21 band, suggesting that this might be the locus of a recessive tumor suppressor gene, the absence of which contributes to malignant transformation or proliferation. Among the seven children with 6q translocations, a previously unidentified nonrandom translocation, t(6;12)(q21;p13) was noted in two cases with an early pre-B immunophenotype. Clinical features and event-free survival were similar among children with or without 6q abnormalities. Overall, children with 6q abnormalities were less likely than those without the abnormality to have a pre-B immunophenotype (P = .03). T-cell immunophenotypes were equally represented in cases with or without 6q abnormalities. However, all four children with del(6q) and a 12p abnormality had early pre-B ALL and all three children with del(6q) and a 9p abnormality had a T-cell immunophenotype. The lack of specificity for a particular immunophenotype may imply that the gene or genes affected by 6q abnormalities are broadly active in the multistep process of lymphoid leukemogenesis. The relatively high frequency of microscopically visible del(6q) indicates the need for molecular studies to identify cases with submicroscopic deletions. .A Hayashi Y; Raimondi SC; Look AT; Behm FG; Kitchingman GR; Pui CH; Rivera GK; Williams DL. .I 274362 .U 91002924 .S Blood 9101; 76(8):1631-8 .M Complement 5a/*PD; Gene Expression; Human; Interleukin-1/BI/*GE/PD; Lipopolysaccharides/*PD; N-Formylmethionine Leucyl-Phenylalanine/PD; Recombinant Proteins/PD; RNA, Messenger/BI; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tetradecanoylphorbol Acetate/PD; Transcription, Genetic/*; Translation, Genetic/*; Tumor Necrosis Factor/BI/*GE. .T Recombinant C5a stimulates transcription rather than translation of interleukin-1 (IL-1) and tumor necrosis factor: translational signal provided by lipopolysaccharide or IL-1 itself. .P JOURNAL ARTICLE. .W We investigated the effects of recombinant C5a (rC5a) on gene expression and synthesis of interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF) in fresh human peripheral blood mononuclear cells (PBMC). Total (cell-associated and secreted) cytokine synthesis was measured. In the strict absence of endotoxin (lipopolysaccharide [LPS]), rC5a resulted in a small but statistically insignificant increase in immunoreactive IL-1 beta and TNF, as well as in IL-1 and IL-6 bioactivity. On the other hand, rC5a induced marked transcriptional activation of IL-1 beta and TNF in a dose-dependent fashion with an optimal concentration of 50 ng/mL. The rC5a-induced cytokine messenger RNA (mRNA) was not spontaneously translated into protein. At 50 ng/mL, rC5a induced the same levels of mRNA for IL-1 beta and TNF as 1 ng/mL of LPS, whereas LPS induced 12 times more IL-1 beta protein and 70 times more TNF protein than rC5a alone. The C5a-induced mRNA half-life was the same as that induced by LPS. Formyl-Meth-Leu-Phe (fMLP) did not induce cytokine transcription. Pretreatment with rC5a enhanced cytokine synthesis induced by other stimuli. After 2 hours of preincubation with rC5a, PBMC synthesized 3 to 10 times more IL-1 beta and TNF on subsequent stimulation by LPS or IL-1 itself. We conclude that rC5a provides primarily a transcriptional but not translational signal for IL-1 beta and TNF; the half-life of the untranslated mRNA is the same as that of translated message; rC5a-induced transcription upregulates PBMC for enhanced synthesis of these cytokines; and a translational signal can be provided by LPS or IL-1 itself. .A Schindler R; Gelfand JA; Dinarello CA. .I 274363 .U 91002925 .S Blood 9101; 76(8):1639-46 .M Antigens, Surface/AN; Bone Marrow/CY; Cell Survival; Cells, Cultured; Flow Cytometry; Fluorescent Antibody Technique; Histocytochemistry; Human; Immunoenzyme Techniques; Immunophenotyping; Leukemia, Promyelocytic, Acute/IM/PA; Neutrophils/*CY/IM; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured. .T The role of cellular maturation in neutrophil heterogeneity. .P JOURNAL ARTICLE. .W Previous studies have shown that many neutrophil (PMN) characteristics are heterogeneous but the origin of PMN heterogeneity is unknown. It is unclear if PMN functional heterogeneity is secondary to maturational differences or due to distinct subpopulations of cells that possess different functional capacities. The PMN 31D8 antigen is a useful probe for evaluation of PMN subpopulations. The majority of PMNs (approximately 85%) exhibit a high intensity fluorescence after 31D8 monoclonal antibody (MoAb) labeling (31D8 enriched or "bright" PMNs) as determined by flow cytometric analysis. These cells are more functional than cells with low intensity fluorescence (31D8 diminished or "dull" PMNs). Various immunologic, clonogenic and functional techniques were used to study the expression of the 31D8 antigen in HL-60 cells and myeloid cells in order to evaluate antigenic and functional heterogeneity during morphologic maturation. The results of this study indicate that the percentage of 31D8 antigen positive (31D8 antigen enriched and diminished) bone marrow cells increases from 20 +/- 11% in myeloblast cells to 68 +/- 10% in promyelocytes, 93 +/- 2% in myelocytes and 99 +/- 1% in bands and PMNs. 31D8 antigen enriched cells first appear at the myelocyte stage (32 +/- 10%) and increase in bands (52 +/- 13%), marrow PMNs (62 +/- 13%) and peripheral blood PMNs (88 +/- 4%). These data indicate that the heterogeneous expression of 31D8 antigen in PMNs is due, at least in part, to maturational differences within the PMN population and raise the possibility that other heterogeneously expressed PMN characteristics are also maturationally derived. They also suggest that 31D8 antigenic expression may be a more precise indicator of myeloid functional maturation than maturation as identified by cellular morphology. .A Krause PJ; Todd MB; Hancock WW; Pastuszak WT; Maderazo EG; Hild DH; Kosciol CM. .I 274364 .U 91002926 .S Blood 9101; 76(8):1647-56 .M Adult; Aging; Antigens, CD/AN; Antigens, Differentiation, B-Lymphocyte/AN; B-Lymphocytes/*CY/IM; Bone Marrow Transplantation/*; Cell Differentiation; Child; Child, Preschool; Comparative Study; Graft vs Host Disease/BL; Human; HLA-DR Antigens/AN; IgG/BI; IgM/BI; Immunophenotyping; Infant, Newborn; Leukocyte Count; Lymphocyte Transformation; Staphylococcus aureus/IM; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; T-Lymphocytes/*PH. .T B-cell differentiation following autologous, conventional, or T-cell depleted bone marrow transplantation: a recapitulation of normal B-cell ontogeny. .P JOURNAL ARTICLE. .W The circulating lymphocytes of 88 consecutive patients following autologous, conventional, or T-cell depleted bone marrow transplantation were serially analyzed for B-cell surface antigen expression and function. In the majority of patients, except for those who developed chronic graft-versus-host disease, the number of circulating CD20+ B cell normalized by the fourth posttransplant month. The earliest detectable B cells normally expressed HLA-DR, CD19, surface immunoglobulin (slg), CD21, Leu-8, and lacked expression of CD10 (CALLA). In addition, the circulating B cells expressed CD1c, CD38, CD5, and CD23 for the first year following transplant, antigens that are normally expressed on a small percentage of circulating B cells in normal adults, but highly expressed on cord blood B cells. Similar to cord blood B cells, patient B cells isolated during the first year following transplant, proliferated normally to Staphylococcus aureus Cowan strain I (SAC), and produced IgM, but minimal or no IgG when stimulated with pokeweed mitogen and SAC, unlike normal adult B cells that produce both. The similar phenotype and function of posttransplant and cord blood B cells, and their similar rate of decline in patients and normal children adds further evidence to support the hypothesis that B-cell differentiation posttransplant is recapitulating normal B-cell ontogeny. .A Small TN; Keever CA; Weiner-Fedus S; Heller G; O'Reilly RJ; Flomenberg N. .I 274365 .U 91002927 .S Blood 9101; 76(8):1657-61 .M Animal; Blood Transfusion/*; Blotting, Western; Cell Line; Female; HTLV Antibodies/AN; HTLV-I/IM/IP; HTLV-I Infections/MI/PC/*TM; Immunization, Passive/*; Interleukin-2/PD; Male; Microscopy, Electron; Rabbits; Support, Non-U.S. Gov't; T-Lymphocytes/MI. .T Transmission of HTLV-I by blood transfusion and its prevention by passive immunization in rabbits. .P JOURNAL ARTICLE. .W To determine the minimum volume of blood required to transmit human T-cell leukemia virus type I (HTLV-I), heparinized blood was collected from a virus-infected female rabbit and aliquots of 10, 5, 1, 0.5, 0.1, and 0.01 mL were transfused into groups of two male rabbits each. All 10 rabbits transfused with 10 to 0.1 mL and 1 of 2 rabbits transfused with 0.01 mL seroconverted for HTLV-I after 2 to 4 weeks. HTLV-I-producing lymphoid cell lines of recipient origin were established from one seroconverted rabbit of each aliquot group. To determine the ability of passive immunization to protect against HTLV-I infection, two groups of three rabbits were first transfused with 5 mL of blood from the same virus-infected rabbit and then infused after 24 or 48 hours with 10 mL of HTLV-I immune globulin (77 mg/mL of IgG) prepared from seropositive healthy persons. None of the 24-hour immunization group seroconverted for HTLV-I during the observation period of six months; however, all of the 48-hour immunization group became seropositive after 2 to 4 weeks. These results indicate that HTLV-I can be transmitted with as little as 0.01 mL of virus-infected blood, and that passive immunization is effective in preventing cell-to-cell infection of HTLV-I when given within 24 hours of transfusion of virus-infected blood. .A Kataoka R; Takehara N; Iwahara Y; Sawada T; Ohtsuki Y; Dawei Y; Hoshino H; Miyoshi I. .I 274366 .U 91002928 .S Blood 9101; 76(8):1663 .M beta 2-Microglobulin/*ME; Adult; Female; Human; Male; Multiple Myeloma/BL/ET; Plasmacytoma/*BL/CO. .T Serum beta 2 microglobulin in solitary plasmocytomata [letter; comment] .P COMMENT; LETTER. .A Aviles A; Huerta J; Zepeda G; Diaz-Maqueo JC. .I 274367 .U 91002929 .S Blood 9101; 76(8):1663-5 .M Aged; Base Sequence; Case Report; Female; Genes, abl/*GE; Human; Leukemia, Myeloid, Chronic/*GE; Molecular Sequence Data; Proto-Oncogene Proteins/*GE; Support, Non-U.S. Gov't; Transcription, Genetic/*. .T Alternative BCR/ABL transcripts in chronic myeloid leukemia [letter; comment] .P COMMENT; LETTER. .A Zaccaria A; Tassinari A; Testoni N; Lauria F; Tura S; Algeri R; Guerrasio A; Rosso C; Saglio G. .I 274368 .U 91002930 .S Blood 9101; 76(8):1665-6 .M Histiocytes/PA; Hodgkin's Disease/*PA; Human; Lymphocytes/PA. .T More on the origin of the Reed-Sternberg cell [letter; comment] .P COMMENT; LETTER. .A Drexler HG. .I 274369 .U 91002931 .S Blood 9101; 76(8):1666-8 .M Blood Platelets/*ME; Cell Adhesion; Drug Contamination/*; Glycoproteins/*AN; Human; Platelet Membrane Glycoproteins/*IP; Receptors, Immunologic/PH. .T Contamination of thrombospondin with vitronectin [letter; comment] .P COMMENT; LETTER. .A Sun X; Mosher DF. .I 274370 .U 91003016 .S BMJ 9101; 301(6750):453-4 .M Asbestosis/*DI/EC; Great Britain; Human; Male; Workmen's Compensation/*/LJ. .T Asbestos diseases and compensation [editorial] [see comments] .P EDITORIAL. .A Seaton A. .I 274371 .U 91003017 .S BMJ 9101; 301(6750):454-5 .M Aspirin/TU; Erythromelalgia/*DI/ET/TH; Human; Rest. .T Three types of erythromelalgia [editorial] [see comments] .P EDITORIAL. .A Drenth JP; Michiels JJ. .I 274372 .U 91003018 .S BMJ 9101; 301(6750):455-6 .M Family Practice/*/OG; Female; Great Britain; Human; Male; Personnel Staffing and Scheduling/*; Salaries and Fringe Benefits; Sex Factors; Time and Motion Studies. .T General practitioners' workload [editorial] .P EDITORIAL. .A Ridsdale L. .I 274373 .U 91003019 .S BMJ 9101; 301(6750):461-6 .M Adult; Aged; Blood Pressure; Calcium/BL; Cardiovascular Diseases/BL/*ET; Cholesterol/*BL; Human; Longitudinal Studies; Male; Middle Age; Risk Factors; Sleep Disorders/*PX; Stress, Psychological/BL; Support, Non-U.S. Gov't; Sweden; Unemployment/*PX. .T Threat of unemployment and cardiovascular risk factors: longitudinal study of quality of sleep and serum cholesterol concentrations in men threatened with redundancy. .P JOURNAL ARTICLE. .W OBJECTIVE--To assess whether the threat of unemployment affects risk factors for cardiovascular disease. DESIGN--Longitudinal study of a cohort of middle aged shipyard workers followed up for a mean of 6.2 (SD 1.9) years and a group of controls observed for the same period. The first investigation took place during a period of relative economic stability for the shipyard and the second during the phase of its closure. SETTING--An age cohort health screening programme in Malmo, Sweden. PARTICIPANTS--715 Male shipyard workers and 261 age matched male controls. MAIN OUTCOME MEASURES--Changes in 19 variables related to the risk of cardiovascular disease, and psychological variables, alcohol consumption, smoking, and dietary habits as assessed by questionnaire. RESULTS--Serum cholesterol concentrations increased more (mean 0.25 (SD 0.68) mmol/l v 0.08 (0.66) mmol/l) and serum calcium concentrations decreased less (-0.06 (0.10) mmol/l v -0.08 (0.09) mmol/l) in the shipyard workers than in the controls. A correlation was found between scores for sleep disturbance and changes in serum cholesterol concentration. In the whole series there was a greater increase in serum cholesterol concentrations among men threatened with unemployment (437/976; 44.8%) than among those who were not. In stepwise regression analysis the change in serum cholesterol concentration was correlated with changes in haemoglobin concentration, body weight, and serum triglyceride and calcium concentrations. A positive correlation was found between change in cholesterol concentration and change in blood pressure, indicating that the overall risk profile had worsened among men with increased serum cholesterol concentrations. CONCLUSIONS--Risk of unemployment increases the serum cholesterol concentration in middle aged men, the increase being more pronounced in those with sleep disturbance. The increase in serum cholesterol is related to changes in other established risk factors for cardiovascular disease. These findings might partly explain the excessive mortality due to cardiovascular disease recorded among the unemployed and people with sleep disturbance. .A Mattiasson I; Lindgarde F; Nilsson JA; Theorell T. .I 274374 .U 91003020 .S BMJ 9101; 301(6750):466-70 .M Adolescence; Adult; Animal; Antimalarials/*TU; Chloroguanide/AD; Chloroquine/AD; Comparative Study; Dapsone/AD; Drug Therapy, Combination; Female; Human; Intervention Studies; Malaria/BL/*DT; Plasmodium falciparum/*; Pregnancy; Pregnancy Complications, Infectious/*DT; Prospective Studies; Pyrimethamine/AD; Sulfadoxine/AD. .T Comparison of chloroquine, pyrimethamine and sulfadoxine, and chlorproguanil and dapsone as treatment for falciparum malaria in pregnant and non-pregnant women, Kakamega District, Kenya. .P CLINICAL TRIAL; JOURNAL ARTICLE. .W OBJECTIVE--To compare treatment and protection against falciparum malaria in pregnant and non-pregnant women with three drug regimens. DESIGN--Prospective intervention study with six weeks' follow up. Patients received one of three drug regimens in order of entry. SETTING--Primary care hospital and secondary girls' school in rural western Kenya. PATIENTS--158 of 988 pregnant women (89 primigravid and 69 multigravid) in the third trimester and 105 of 1488 non-pregnant schoolgirls of reproductive age were parasitaemic (more than 500 asexual forms/microliter. These women were divided into three treatment groups by gravid state. INTERVENTIONS--Women were treated with chloroquine base 25 mg/kg over three days or pyrimethamine 75 mg and sulfadoxine 1500 mg as a single dose or chlorproguanil 1.2 mg/kg and dapsone 2.4 mg/kg as a single dose. MAIN OUTCOME MEASURES--Parasitaemia and haemoglobin concentrations measured at seven day intervals for six weeks. RESULTS--Primigravid women were more likely to be parasitaemic on follow up than multigravidas or nulligravidas, whose response was about the same. Parasites did not clear by day 7 in primigravidas in six (20%) of 30 who received chloroquine, three (8%) of 35 treated with pyrimethamine and sulfadoxine, and none of 23 treated with chlorproguanil and dapsone. At day 28, 83%, 19%, and 67% of primigravidas in these treatment groups were parasitaemic. Haemoglobin concentrations rose in all women, but improvement was sustained only in women who remained free of parasites. CONCLUSIONS--Clearance of parasites was better with either pyrimethamine and sulfadoxine or chlorproguanil and dapsone than with chloroquine. Longest protection was obtained with pyrimethamine and sulfadoxine. .A Keuter M; van Eijk A; Hoogstrate M; Raasveld M; van de Ree M; Ngwawe WA; Watkins WM; Were JB; Brandling-Bennett AD. .I 274375 .U 91003021 .S BMJ 9101; 301(6750):470-3 .M Appointments and Schedules; Correspondence/*; Education, Medical, Continuing; England; Human; Interprofessional Relations; Orthopedics/*/ED/ST; Outpatient Clinics, Hospital/*ST; Referral and Consultation/*SN; Retrospective Studies; Support, Non-U.S. Gov't; Time Factors. .T Referral letters and replies from orthopaedic departments: opportunities missed [see comments] .P JOURNAL ARTICLE. .W OBJECTIVE--To study delays between sending referral letters and the outpatient appointment and to assess the content of referral and reply letters, their educational value, and the extent to which questions asked are answered by reply letters. DESIGN--Retrospective review of referrals to 16 consultant orthopaedic surgeons at five hospitals, comprising 288 referral letters with corresponding replies, by scoring contents of letters. SETTING--Orthopaedic teaching hospitals in Nottingham, Derby, and Mansfield. MAIN OUTCOME MEASURES--Weighted scores of contents of referral and reply letters, assessment of their educational value, and responses to questions in referral letters. RESULTS--Median outpatient delay was 23.4 weeks. There was no significant decrease in waiting time if the referral letter was marked "urgent" but a significantly greater delay (p less than 0.01) if referrals were directed to an unnamed consultant. The content score was generally unsatisfactory for both referrals and replies, and there was no correlation for the content scores of the referral letter and its reply (r = 0.13). Items of education were rare in the referral letters (8/288; 3%) and significantly more common in replies (75/288; 26%) (p much less than 0.001). Senior registrars were significantly more likely to attempt education than other writers (p less than 0.02). Education in replies was significantly related to increased length of the letter (p less than 0.05) and was more likely to occur if the referral was addressed to a named consultant (p less than 0.03). 48 (17%) Referral letters asked questions, of which 21 (44%) received a reply. No factor was found to influence the asking of or replying to questions. CONCLUSIONS--The potential for useful communication in the referral letter and in the reply from orthopaedic surgeons is being missed at a number of levels. The content is often poor, the level of mutual education is low, and the use of the referral letter to determine urgency is deficient. Most questions asked by general practitioners are not answered. .A Jacobs LG; Pringle MA. .I 274376 .U 91003022 .S BMJ 9101; 301(6750):473-6 .M Adult; Asthma/*BL/DT/PP; Atropine/TU; Circadian Rhythm; Double-Blind Method; Epinephrine/*BL/TU; Female; Human; Male; Middle Age; Peak Expiratory Flow Rate/DE; Time Factors. .T Adrenaline and nocturnal asthma. .P CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL. .W OBJECTIVE--To determine whether the nocturnal fall in plasma adrenaline is a cause of nocturnal asthma. DESIGN--Double blind placebo controlled cross-over study. In the first experiment the nocturnal fall in plasma adrenaline at 4 am was corrected in 10 asthmatic subjects with an infusion of adrenaline after parasympathetic blockade with 30 micrograms/kg intravenous atropine. In the second experiment 11 asthmatic subjects showing similar variations in peak expiratory flow rate had the nocturnal fall in plasma adrenaline corrected by infusion before atropine was given. PATIENTS--Asthmatic subjects with a diurnal variation in home peak expiratory flow rate of greater than 20% for at least 75% of the time in the two weeks before the study. MAIN OUTCOME MEASURES--Peak expiratory flow rate and plasma adrenaline. RESULTS--Correction of the nocturnal fall in plasma adrenaline at 4 am to resting 4 pm levels did not alter peak expiratory flow rate either before or after parasympathetic blockade with atropine. CONCLUSION--A nighttime fall in plasma adrenaline is not a cause of nocturnal asthma. .A Morrison JF; Teale C; Pearson SB; Marshall P; Dwyer NM; Jones S; Dean HG. .I 274377 .U 91003023 .S BMJ 9101; 301(6750):476-7 .M Anemia/*DT/ET; Case Report; Erythropoietin/*TU; Female; Hemodialysis; Hemoglobins/AN; Human; Kidney Failure, Chronic/CO/TH; Male; Middle Age; Multiple Myeloma/BL/*CO; Support, Non-U.S. Gov't. .T Effect of erythropoietin on anaemia in patients with myeloma receiving haemodialysis. .P JOURNAL ARTICLE. .A Taylor J; Mactier RA; Stewart WK; Henderson IS. .I 274378 .U 91003024 .S BMJ 9101; 301(6750):478-80 .M Attitude of Health Personnel; Clinical Competence; England; Family Practice/*; Female; Human; Male; Physical Examination/*; Questionnaires; Rectal Diseases/*DI; Sex Factors; Support, Non-U.S. Gov't. .T Rectal examination in general practice [see comments] .P JOURNAL ARTICLE. .W OBJECTIVE--To investigate factors influencing a general practitioner's decision to do a rectal examination in patients with anorectal or urinary symptoms. DESIGN--Postal questionnaire survey. SETTING--General practices in inner London and Devon. SUBJECTS--859 General practitioners, 609 (71%) of whom returned the questionnaire. MAIN OUTCOME MEASURES--Number of rectal examinations done each month; the indication score, derived from answers to a question asking whether the respondent would do a rectal examination for various symptoms; and the confidence score, which indicated the respondent's confidence in the diagnosis made on rectal examination. RESULTS--279 General practitioners did five or fewer rectal examinations each month and 96 did more than 10 each month. Factors significantly associated with doing fewer rectal examinations were a small partnership and being a female general practitioner, and the expectation that the examination would be repeated. Lack of time in the surgery, and a waiting time of less than two weeks for an urgent outpatient appointment were also important. General practitioners were deterred from doing rectal examinations by reluctance of the patient (278), the expectation that the examination would be repeated (141), and lack of time (123) or a chaperone (39). Confidence in diagnosis was significantly associated with doing more rectal examinations, the perception of having been well taught to do a rectal examination at medical school, and being a male general practitioner. CONCLUSIONS--Factors other than clinical judgment influence the frequency of rectal examination in general practice. Rectal examination may become commoner with the trend towards larger group practices and if diagnostic confidence is increased and greater emphasis put on rectal examination in undergraduate and postgraduate teaching. .A Hennigan TW; Franks PJ; Hocken DB; Allen-Mersh TG. .I 274379 .U 91003025 .S BMJ 9101; 301(6750):481-4 .M Forecasting; Great Britain; Policy Making; Public Health Administration/*TD; State Medicine/*OG; Support, Non-U.S. Gov't. .T What future for the Department of Health? .P JOURNAL ARTICLE. .A Klein R. .I 274380 .U 91003026 .S BMJ 9101; 301(6750):485-8 .M Adult; Child; Hematuria/ET; Human; Kidney/*IN/RA; Nephrectomy; Wounds, Nonpenetrating/*/SU; Wounds, Penetrating/*/SU. .T ABC of major trauma. Trauma of the upper urinary tract. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .A Terry T. .I 274381 .U 91003027 .S BMJ 9101; 301(6750):489-90 .M Case Report; Gastrinoma/*PA/SU; Glucagonoma/PA; Human; Male; Middle Age; Neoplasms, Multiple Endocrine/*PA/SU; Pancreatic Neoplasms/*PA/SU; Support, Non-U.S. Gov't. .T Gastrinoma syndrome in multiple endocrine neoplasia [clinical conference] .P CLINICAL CONFERENCE; JOURNAL ARTICLE. .A Wynick D; Dollery CT; Bloom SR; Polak JM; Lynn JA. .I 274382 .U 91003028 .S BMJ 9101; 301(6750):492 .M Formularies/*; Great Britain; Prescriptions, Drug/*EC. .T Interpretation and management of PACT (prescribing analysis and cost) data on formularies [letter] [see comments] .P LETTER. .A Anderson ML; Barrett CW; Kopelman PG. .I 274383 .U 91003029 .S BMJ 9101; 301(6750):492-4 .M Bedding and Linens/*; Human; Infant; Posture; Sleep/*PH; Sudden Infant Death/*ET. .T Bedding and sleeping position in the sudden infant death syndrome [letter] [published erratum appears in BMJ 1990 Oct 10;301(6756):875] .P LETTER. .I 274384 .U 91003030 .S BMJ 9101; 301(6750):494-5 .M Bleeding Time/*; Hemorrhage/PC; Human; Liver Cirrhosis/*BL; Risk Factors. .T Bleeding time in patients with hepatic cirrhosis [letter; comment] .P COMMENT; LETTER. .A Burroughs AK; Blake J. .I 274385 .U 91003031 .S BMJ 9101; 301(6750):495 .M Child; Human; Lidocaine/*AE; Methemoglobinemia/*CI; Ointments; Prilocaine/*AE. .T Methaemoglobinaemia in children treated with prilocaine-lignocaine cream [letter; comment] .P COMMENT; LETTER. .A Radford M; Pinder AM. .I 274386 .U 91003032 .S BMJ 9101; 301(6750):495-6 .M Anesthesia, Local; Colles' Fracture/*TH; Fracture Fixation/MT; Human. .T Colles' fracture [letter; comment] .P COMMENT; LETTER. .I 274387 .U 91003033 .S BMJ 9101; 301(6750):496 .M Adult; Animal; Athletic Injuries/*EP; Great Britain/EP; Horses/*; Human; Risk Factors. .T Safety of horseriding [letter] .P LETTER. .A Nicholl JP. .I 274388 .U 91003035 .S BMJ 9101; 301(6751):502-3 .M Child; Child Health Services/*ST; Diabetes Mellitus, Insulin-Dependent/CO/*TH; Great Britain; Human; Quality of Health Care/SN. .T Children with diabetes [editorial] .P EDITORIAL. .A Baum JD. .I 274389 .U 91003036 .S BMJ 9101; 301(6751):503-4 .M Aged; Arthritis/DI; Human; Joint Diseases/DI/PP/TH; Pain/*ET; Shoulder Joint/*. .T Shoulder pain in the elderly [editorial] [see comments] .P EDITORIAL. .A O'Reilly D; Bernstein RM. .I 274390 .U 91003037 .S BMJ 9101; 301(6751):504-6 .M Child, Preschool; Cognition Disorders/ET; Environmental Exposure/*; Human; Infant; Lead/*/BL; Lead Poisoning/BL/CO/*ET. .T Low level exposure to lead [editorial] [see comments] .P EDITORIAL. .A Lee WR; Moore MR. .I 274391 .U 91003038 .S BMJ 9101; 301(6751):506 .M Allied Health Personnel/*ED; Educational Measurement; Great Britain; State Medicine; Vocational Education/*MT. .T Training for care assistants [editorial] [see comments] .P EDITORIAL. .A Murphy E. .I 274392 .U 91003040 .S BMJ 9101; 301(6751):513-5 .M Adult; Age Factors; Aged; Dyspepsia/*ET; Gastroscopy; Human; Middle Age; Neoplasm Staging; Precancerous Conditions/DI; Prospective Studies; Stomach Neoplasms/CO/*DI/PA; Support, Non-U.S. Gov't. .T Early detection of gastric cancer [see comments] .P CLINICAL TRIAL; JOURNAL ARTICLE. .W OBJECTIVE--To see whether investigation of dyspeptic patients aged over 40 after their first consultation with the general practitioner would increase the proportions with early and operable gastric cancers. DESIGN--Prospective study of gastric cancer in dyspeptic patients aged over 40 from a defined population. SETTING--10 General practices (six in central Birmingham, four in Sandwell); the Queen Elizabeth Hospital, Birmingham; and Sandwell District General Hospital. PATIENTS--2659 Patients aged 40 or over referred with dyspepsia. MAIN OUTCOME MEASURE--Increase in early and operable gastric cancers detected in middle aged patients with dyspepsia. RESULTS--Disease was identified in 1992 patients (75%). Fifty seven were found to have gastric cancer, 36 being treated by potentially curative resection, including 15 with early cancer. CONCLUSIONS--The investigation of dyspeptic patients over 40 at first attendance can increase the proportion of early gastric cancers detected to 26% and the proportion of operable cases to 63%. Such a policy has the potential to reduce mortality from gastric cancer in the population. .A Hallissey MT; Allum WH; Jewkes AJ; Ellis DJ; Fielding JW. .I 274393 .U 91003041 .S BMJ 9101; 301(6751):516-8 .M Adult; Amenorrhea/*PA; Bone Density/*; Comparative Study; Cross-Sectional Studies; Dancing; Exercise/*; Female; Human; Lumbar Vertebrae/*PA; Muscle Contraction; Sports/*; Support, Non-U.S. Gov't. .T Menstrual state and exercise as determinants of spinal trabecular bone density in female athletes. .P JOURNAL ARTICLE. .W OBJECTIVE--To study the effects of amenorrhoea and intensive back exercise on the bone mineral density of the lumbar spine in female athletes. DESIGN--Cross sectional study comparing amenorrhoeic with eumenorrhoeic athletes and rowers with non-rowers. SETTING--The British Olympic Medical Centre, Northwick Park Hospital. PATIENTS--46 Elite female athletes comprising 19 rowers, 18 runners, and nine dancers, of whom 25 were amenorrhoeic and 21 eumenorrhoeic. MAIN OUTCOME MEASURE--Trabecular bone mineral density of the lumbar spine measured by computed tomography. RESULTS--Mean trabecular bone mineral density was 42 mg/cm3 (95% confidence interval 22 to 62 mg/cm3) lower in the amenorrhoeic than the eumenorrhoeic athletes; this difference was highly significant (p = 0.0002). Mean trabecular bone mineral density was 21 mg/cm3 (1 to 41 mg/cm3) lower in the non-rowers than the rowers; this was also significant (p = 0.05). There was no interaction between these two effects (p = 0.28). CONCLUSION--The effect of intensive exercise on the lumbar spine partially compensates for the adverse effect of amenorrhoea on spinal trabecular bone density. .A Wolman RL; Clark P; McNally E; Harries M; Reeve J. .I 274394 .U 91003042 .S BMJ 9101; 301(6751):518-20 .M Acquired Immunodeficiency Syndrome/*EP/PC/TM; Adult; Female; Human; HIV Seropositivity/*EP; HIV-1/*; Mass Screening/MT; Middle Age; Pregnancy; Pregnancy Complications, Infectious/*EP; Prenatal Care/*; Retrospective Studies; Risk Factors; Scotland/EP. .T Prevalence of HIV antibody and pregnancy in Tayside, 1984-9: background to screening. .P JOURNAL ARTICLE. .W OBJECTIVE--To determine age specific prevalence of HIV antibody, incidence of pregnancy, and likelihood of detection and correct assignment to risk category by antenatal screening of women known to be positive for HIV antibody, from 1984 to 1989. DESIGN--Retrospective analysis of reproductive history and risk behaviour of women positive for HIV antibody and prediction of detection by screening on the basis of blood group samples, Guthrie tests, and rubella tests. SETTING--City of Dundee, where the prevalence of HIV is high, since the appearance of HIV in 1984, predominantly among heterosexual intravenous drug users. PATIENTS--All (61) women known to be positive for HIV antibody who had had clinically indicated tests, for whom case notes were available for 60. MAIN OUTCOME MEASURES--Risk assessment according to case notes and reported to the laboratory, incidence of infection, geographical location, age, date of positive test result, and reproductive history. RESULTS--With 61 infected women the overall minimum prevalence among women within the city of Dundee was 0.67/1000 and 2.9/1000 among women in their third decade. Of the 60 women whose reproductive history was available, 35 had 57 pregnancies, 36 of which occurred after seroconversion was known to have taken place, representing 8.7% of the total number of affected pregnancies reported for the United Kingdom. If antenatal screening for HIV had been performed between 1984 and 1989 it could not have detected positivity for HIV antibody in 25 (42%) women who had no pregnancies during this time. Among the remaining 35 women, screening samples taken for blood grouping could have identified a maximum of 34 (57%), samples taken to check rubella susceptibility a maximum of 22 (37%), and blood spots on Guthrie cards a maximum of 19 (32%). Retesting would have occurred in 14 women 33 times with samples taken for blood grouping, but three and four women would have been tested twice using samples taken for rubella testing and Guthrie cards respectively. Anonymous screening would have been unable to determine risk category as a history of intravenous drug use was known in 47 (79%) women before testing but this was increased by a further 5 (8%) who admitted to it after the test result was known. CONCLUSION--Interpreting the results of antenatal screening programmes will be complex and will underestimate overall prevalence of HIV antibody among women; this will be exaggerated by strategies based on anonymous testing with Guthrie cards or on samples taken for rubella testing, which do not include women who have had an earlier loss of pregnancy. Only open testing with consent will permit satisfactory attribution to .A Smith R; Patel NB; Urquhart GE; McFaul P; Neven P; Howie PW. .I 274395 .U 91003043 .S BMJ 9101; 301(6751):521-3 .M Adult; Cholesterol/BL; Double-Blind Method; Drug Combinations; Female; Human; Hypertension/BL/*DT; Magnesium Chloride/AD/*TU; Male; Middle Age; Potassium Chloride/AD/*TU. .T Efficacy of potassium and magnesium in essential hypertension: a double-blind, placebo controlled, crossover study [see comments] .P CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL. .W OBJECTIVE--To evaluate the antihypertensive activity of potassium given alone or in combination with magnesium in patients with mild hypertension. DESIGN--A double blind, randomised, placebo controlled, crossover trial of 32 weeks' duration. SETTINGS--Cardiology outpatient department, Sassoon General Hospitals, Pune, India. PATIENTS--37 Adults with mild hypertension (diastolic blood pressure less than 110 mm Hg). INTERVENTION--Patients received either placebo or potassium 60 mmol/day alone or in combination with magnesium 20 mmol/day in a crossover design. No other drug treatment was allowed. MEASUREMENTS--Blood pressure and heart rate assessed at weekly intervals and biochemical parameters at monthly intervals. RESULTS--Potassium alone or in combination with magnesium produced a significant reduction in systolic and diastolic blood pressures (p less than 0.001) and a significant reduction in serum cholesterol concentration (p less than 0.05); other biochemical variables did not change. Magnesium did not have an additional effect. Urinary potassium excretion increased significantly in the groups who received potassium alone or in combination with magnesium. The drug was well tolerated and compliance was satisfactory. CONCLUSION--Potassium 60 mmol/day lowers arterial blood pressure in patients with mild hypertension. Giving magnesium as well has no added advantage. .A Patki PS; Singh J; Gokhale SV; Bulakh PM; Shrotri DS; Patwardhan B. .I 274396 .U 91003044 .S BMJ 9101; 301(6751):523-4 .M Adolescence; Anemia, Sickle Cell/IM/TH; Blood Transfusion/*AE; Cameroon; Case-Control Studies; Child; Child, Preschool; Hepatitis B/*TM; Hepatitis B Surface Antigens/AN; Human; Infant; Support, Non-U.S. Gov't. .T Transmission of hepatitis B virus by blood transfusion in Yaounde, Cameroon. .P JOURNAL ARTICLE. .A Ndumbe PM; Nyouma E. .I 274397 .U 91003045 .S BMJ 9101; 301(6751):524-5 .M Adult; Aged; Aged, 80 and over; Female; Human; Middle Age; Ovarian Neoplasms/*ET/PA/PP; Ovulation/*PH. .T Aetiological importance of ovulation in epithelial ovarian cancer: a population based study [published erratum appears in BMJ 1990 Sep 29;301(6753):646] [see comments] .P JOURNAL ARTICLE. .A Cruickshank DJ. .I 274398 .U 91003046 .S BMJ 9101; 301(6751):525 .M Acquired Immunodeficiency Syndrome/*TM; Adolescence; Adult; Contraceptive Devices, Male; Equipment Failure; Female; Human; Male; Middle Age; Prostitution/*; Risk Factors; Scotland; Sex Behavior; Support, Non-U.S. Gov't. .T Risk of HIV infection among clients of the sex industry in Scotland. .P JOURNAL ARTICLE. .A Thomas RM; Plant MA; Plant ML; Sales J. .I 274399 .U 91003047 .S BMJ 9101; 301(6751):526-9 .M Attitude of Health Personnel; Evaluation Studies; Hospital Bed Capacity, 500 and over; London; Medical Audit/*OG; Medical Records/ST; Medical Staff, Hospital/*ST; Questionnaires; Random Allocation; Statistics. .T What did audit achieve? Lessons from preliminary evaluation of a year's medical audit [see comments] .P JOURNAL ARTICLE. .W OBJECTIVE--To evaluate the experience of a year's audit of care of medical inpatients. DESIGN--Audit of physicians by monthly review of two randomly selected sets of patients' notes by 12 reviewers using a detailed questionnaire dedicated to standards of medical records and to clinical management. Data were entered into a database and summary statistics presented quarterly at audit meetings. Assessment by improvement in questionnaire scores and by interviewing physicians. SETTING--1 District general hospital. PARTICIPANTS--About 40 consultant physicians, senior registrars, and junior staff dealing with 140 inpatient records. MAIN OUTCOME MEASURES--Median scores (range 1 to 9) for each item in the questionnaire; two sets of notes were discussed monthly at "general" audit meetings and clinical management of selected common conditions at separate monthly meetings. RESULTS--A significant overall increase in median scores for questions on record keeping occurred after the start of the audit (p less than 0.01), but interobserver variation was high. The parallel audit meetings on clinical management proved to be more successful than the general audits in auditing medical care and were also considered to be more useful by junior staff. CONCLUSIONS AND ACTION--Medical audit apparently resulted in appreciable improvements in aspects of care such as clerking and record keeping. Analysis of the scores of the general audits has led to the introduction of agreed standards that can be objectively measured and are being used in a further audit, and from the results of the audits of clinical management have been developed explicit guidelines, which are being further developed for criterion based audit. .A Gabbay J; McNicol MC; Spiby J; Davies SC; Layton AJ. .I 274400 .U 91003048 .S BMJ 9101; 301(6751):529-31 .M Communication; Emergency Service, Hospital/*OG; England; Human; Medical Staff, Hospital/*; Outcome and Process Assessment (Health Care)/*SN; Patient Admission/*; Support, Non-U.S. Gov't; Telephone; Time Factors; Wales. .T How easy is it to contact the duty medical doctor responsible for acute admissions? [see comments] .P JOURNAL ARTICLE. .W OBJECTIVE--To ascertain ease or difficulty of contacting duty junior doctors responsible for acute medical admissions by telephone. DESIGN--Telephone survey of hospitals in six health regions in England and Wales. SETTING--70 Randomly selected hospitals, 15 of which were excluded because of non-acceptance of acute medical admissions. PARTICIPANTS--71 Duty doctors (duty house physicians, senior house officers, or registrars responsible for acute medical admissions) in 48 hospitals; seven duty doctors in seven hospitals were excluded (four declined to participate and three required a written explanation of the survey). 67 Doctors gave full information to all questions. MAIN OUTCOME MEASURES--Time taken for hospital switchboards and duty doctors to reply to telephone call, diagnoses of patients recently admitted, and on call rotas and hours of sleep of duty doctors. RESULTS--Hospital switchboards responded within 30 seconds in 87 (74%) calls, and in 76 calls (64%) the duty doctor requested was contacted within a further two minutes. Chest pain, possibly due to myocardial infarction, was the most common reason for acute medical admissions. Nearly half (48%) of the duty doctors in larger hospitals reported having 4-5 hours sleep or less on their nights on call. Most (30) were on a one in three rota; two were on a one in two rota. CONCLUSIONS--Despite impressions to the contrary contacting the duty medical team by telephone seemed fairly easy. Although most junior doctors were on a rota of one in three or better, insufficient recognition may be given to their deprivation of sleep during nights on duty. .A Bakhai A; Goodman F; Juchniewichz H; Martin A; Porter G; White C; Williams L; Hopkins A. .I 274401 .U 91003049 .S BMJ 9101; 301(6751):531-2 .M Great Britain; Health Services Research; Human; Patient Admission/*; Physician's Practice Patterns/*; Quality of Health Care/*ST; United States. .T Variations in hospital admissions and the appropriateness of care: American preoccupations? .P JOURNAL ARTICLE. .A Bunker JP. .I 274402 .U 91003050 .S BMJ 9101; 301(6751):535-40 .M Adolescence; Adult; Aged; Child; Child, Preschool; Comparative Study; Diabetes Mellitus/MO; Diabetic Neuropathies/MO/*TH; England/EP; Graft Survival; Human; Kidney Failure, Chronic/MO/*TH; Kidney Transplantation/*; Middle Age; Pancreas Transplantation; Peritoneal Dialysis, Continuous Ambulatory/*; Postoperative Complications; Retrospective Studies; Support, Non-U.S. Gov't; Survival Rate. .T Renal replacement treatment for diabetic patients in Newcastle upon Tyne and the Northern region, 1964-88. .P CLINICAL TRIAL; JOURNAL ARTICLE. .W OBJECTIVES--To review the experience of renal replacement treatment in diabetic patients treated in Newcastle upon Tyne and the Northern region from 1964 to 1988, and to compare the morbidity and mortality of diabetic patients treated with dialysis or transplantation with those of matched controls of non-diabetic patients. DESIGN--Retrospective study of clinical case notes. SETTING--Renal units of the Northern region, particularly that in Newcastle upon Tyne. PATIENTS--All 65 diabetic patients treated by renal replacement treatment in Newcastle upon Tyne from 1964 to 1987; 42 diabetic patients were matched with 42 non-diabetic patients according to age, sex, year of starting treatment, and type of treatment (dialysis or transplantation). MAIN OUTCOME MEASURES--Sex, age, renal biopsy findings, blood pressure, history of diabetic treatment, and plasma creatinine concentration at the start of renal replacement treatment. History of renal replacement treatments, suitability for transplantation, history of transplantation, cumulative survival, and cause of death during follow up. Survival of technique, cumulative survival of the first peritoneal catheter and history of peritonitis in patients treated with continuous ambulatory peritoneal dialysis; source of graft, histocompatibility antigens, duration of associated stay in hospital, and graft survival in patients receiving renal or pancreatic transplant. RESULTS--1259 Patients with chronic renal failure were accepted for renal replacement treatment in Newcastle upon Tyne, of whom 65 (5%) had diabetes. The first was accepted in 1974, and between 1974 and 1980 another 15 were treated (mean age 42 years; 4% of new patients). From 1981 to 1987, 49 diabetic patients (mean age 44; 9% of new patients) were treated. Fifty patients (77%) had insulin dependent diabetes and the remaining 15 (23%) non-insulin dependent diabetes. On average, the patients were aged 25 (range 5-57) when diabetes was first diagnosed and 44 (range 24-70) at the start of renal replacement treatment. The mean age at the start of treatment was 40 for patients with non-insulin dependent diabetes and 58 for patients with non-insulin dependent diabetes. Transplantation was performed in 33 of the diabetic patients, whose mean age was lower than that of those who did not receive a transplant (41 v 48 respectively, p less than 0.05). Comparison between the 42 diabetic patients and matched controls showed that the overall survival at five years was 46% and 77% respectively. The three year survival of the diabetic patients who did not receive a transplant was poor (41% v 79% respectively). Of patients transplanted, survival at five years was 73% in the diabetic patients and 90% in the controls. However, there was no significant difference in the five year graft survival (64% v 46% respectively). CONCLUSIONS--Diabetes adversely affects morbidity and mortality in patients having renal replacement treatment, but renal transplantation seems to be the best option for treating diabetic patients with end stage renal failure. .A Catalano C; Goodship TH; Tapson JS; Venning MK; Taylor RM; Proud G; Tunbridge WM; Elliot RW; Ward MK; Alberti KG; et al. .I 274403 .U 91003051 .S BMJ 9101; 301(6751):540-4 .M Adult; Aged; Coronary Disease/CO; Diabetes Mellitus, Insulin-Dependent/MO; Diabetes Mellitus, Non-Insulin-Dependent/MO; Diabetic Angiopathies/CO; Diabetic Neuropathies/MO/*TH; Female; Graft Survival; Human; Kidney Failure, Chronic/CO/MO/*TH; Kidney Transplantation/*/UT; Male; Middle Age; Outcome and Process Assessment (Health Care)/*SN; Peritoneal Dialysis, Continuous Ambulatory/*/UT; Retrospective Studies; Scotland/EP; Survival Rate. .T Outcome of renal replacement treatment in patients with diabetes mellitus. .P CLINICAL TRIAL; JOURNAL ARTICLE. .W OBJECTIVE--To compare the outcome of renal replacement treatment in patients with diabetes mellitus and in non-diabetic patients with end stage renal failure. DESIGN--Retrospective comparison of cases and matched controls. SETTING--Renal unit, Western Infirmary, Glasgow, providing both dialysis and renal transplantation. PATIENTS--82 Diabetic patients starting renal replacement treatment between 1979 and 1988, compared with 82 matched non-diabetic controls with renal failure and 39 different matched controls undergoing renal transplantation. MAIN OUTCOME MEASURES--Patient characteristics, history of smoking, prevalence of left ventricular hypertrophy and myocardial ischaemia at start of renal replacement treatment; survival of patients with renal replacement treatment and of patients and allografts with renal transplantation. RESULTS--The overall survival of the diabetic patients during the treatment was 83%, 59%, and 50% at one, three, and five years. Survival was significantly poorer in the diabetic patients than the controls (p less than 0.001). Particularly adverse features for outcome at the start of treatment were increasing age (p less than 0.01) and current cigarette smoking (relative risk (95% confidence interval) 2.28 (0.93 to 4.84), p less than 0.05). Deaths were mainly from cardiac and vascular causes. The incidence of peritonitis in patients on continuous ambulatory peritoneal dialysis was the same in diabetic patients and controls (49% in each group remained free of peritonitis after one year), and the survival of renal allografts was not significantly worse in diabetic patients (p less than 0.5). CONCLUSIONS--Renal replacement treatment may give good results in diabetic patients, although the outlook remains less favourable than for non-diabetic patients because of coexistent, progressive vascular disease, which is more severe in older patients. .A McMillan MA; Briggs JD; Junor BJ. .I 274404 .U 91003052 .S BMJ 9101; 301(6751):545-7 .M Bladder/IN; Bulbourethral Glands/IN; Emergencies; Female; Genitalia, Male/IN; Human; Male; Urethra/IN; Urinary Tract/*IN; Wounds and Injuries/TH. .T ABC of major trauma. Trauma of the lower urinary tract. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .A Deane A. .I 274405 .U 91003053 .S BMJ 9101; 301(6751):551 .M Child; Drug Information Services/*; Great Britain; Human; Risk Factors; Vaccination/*. .T Vaccinations and professional confusion [letter] .P LETTER. .A Elliman D. .I 274406 .U 91003054 .S BMJ 9101; 301(6751):551-2 .M Adult; Birth Weight/*; Female; Human; Hypertension/*ET; Infant, Newborn; Placenta/*AH; Pregnancy; Risk Factors. .T Fetal and placental size and risk of hypertension in adult life [letter; comment] .P COMMENT; LETTER. .I 274407 .U 91003056 .S BMJ 9101; 301(6751):555 .M Acquired Immunodeficiency Syndrome/*PA/US; Biopsy, Needle/IS; Brain/*PA; Echoencephalography; Human. .T Cerebral mass lesions in patients with AIDS [letter] .P LETTER. .A Hately W; Borgstein RL; Hamlyn PJ. .I 274408 .U 91003057 .S BMJ 9101; 301(6751):555 .M Headache/*ET; Human; Nomenclature; Subarachnoid Hemorrhage/*CO. .T Warning leak in subarachnoid haemorrhage [letter; comment] .P COMMENT; LETTER. .I 274409 .U 91003058 .S BMJ 9101; 301(6751):555-6 .M Female; Glucocorticoids, Topical/TU; Human; Skin Diseases/*TH; Vulva/SU; Vulvar Diseases/*TH. .T Treatment for lichen sclerosus [letter] .P LETTER. .A Neill S. .I 274410 .U 91003059 .S BMJ 9101; 301(6751):556 .M Costs and Cost Analysis/MT; England; Human; Medical Audit/*MT; Otorhinolaryngologic Diseases/SU; Surgery, Operative/*EC. .T Caseload or workload? [letter; comment] .P COMMENT; LETTER. .A George SL; Brazier JE. .I 274411 .U 91003060 .S BMJ 9101; 301(6751):556 .M Electroconvulsive Therapy/*; Human; Nerve Tissue/TR; Parkinson Disease/*TH. .T Cell implantation in Parkinson's disease [letter; comment] .P COMMENT; LETTER. .A Madeley P; Boyd JL; Biggins CA; Mindham RH; Spokes EG. .I 274412 .U 91003061 .S BMJ 9101; 301(6751):556 .M Bacterial Infections/*CO; Female; Human; Urinary Incontinence/*ET/PX; Urinary Tract Infections/*CO. .T Psychiatric aspects of urinary incontinence [letter; comment] .P COMMENT; LETTER. .A Maskell R. .I 274413 .U 91003062 .S BMJ 9101; 301(6751):556-7 .M Anesthesiology/*/ED; Child; Education, Medical, Continuing; Great Britain; Human; Pediatrics/*/ED; Societies, Medical/*. .T Perioperative deaths among children [letter; comment] .P COMMENT; LETTER. .A Glover WJ. .I 274414 .U 91003064 .S BMJ 9101; 301(6751):557 .M Alanine Aminotransferase/BL; Aspartate Aminotransferase/BL; Human; Liver Diseases/BL; Liver Function Tests/*MT. .T Liver function tests [letter; comment] .P COMMENT; LETTER. .A Cramb R; Florkowski CM. .I 274415 .U 91003065 .S BMJ 9101; 301(6751):557 .M England; Hospital Units; Human; Peptic Ulcer Hemorrhage/*MO. .T Mortality in patients with bleeding peptic ulcer [letter; comment] .P COMMENT; LETTER. .A Clements D; Stamatakis J; Foster D; Wilkins WE; Morris JS. .I 274416 .U 91003208 .S Br J Urol 9101; 66(3):225-31 .M Female; Fetal Diseases/*/US; Human; Pregnancy; Ultrasonography, Prenatal; Urologic Diseases/*EM/US. .T Fetal uropathy. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .A Thomas DF. .I 274417 .U 91003209 .S Br J Urol 9101; 66(3):232-9 .M Bladder Calculi/*CH; Human; Spectrometry, Gamma; Spectrometry, X-Ray Emission; Support, Non-U.S. Gov't; Trace Elements/AN. .T Nuclear techniques for the analysis of urinary calculi. .P JOURNAL ARTICLE. .W Sections of urinary calculi were prepared and point-by-point analyses along a line-scan were carried out using the techniques of proton-induced X-ray emission (PIXE) and nuclear reaction analysis (NRA). Correlations between several pairs of elements (including trace elements) were noted and it was also clear that the composition of a stone varied markedly at different stages of development. .A Saint A; Dyson NA. .I 274418 .U 91003210 .S Br J Urol 9101; 66(3):240-4 .M Calcium Oxalate/*CH; Citrates/*PD; Crystallization; Mucins/*PD; Pentosan Sulfuric Polyester/*PD; Support, Non-U.S. Gov't. .T Study of factors affecting calcium oxalate crystalline aggregation. .P JOURNAL ARTICLE. .W A study was made of the effects of citrate, pentosan polysulphate (a glycosaminoglycan) and mucin (a mucoprotein) upon crystalline growth and aggregation of calcium oxalate in synthetic urine. It was found that citrate inhibited aggregation. Pentosan polysulphate had no perceptible effect on aggregation but favoured the formation of calcium oxalate dihydrate crystals. Mucin enhanced the formation of large characteristic aggregates and also led to the formation of calcium oxalate dihydrate crystals. Particles of mucin in a solution served as a substrate on which several crystals of calcium oxalate dihydrate were formed by heterogeneous nucleation; the subsequent growth of these crystals resulted in the formation of large agglomerates. .A Grases F; Costa-Bauza A. .I 274419 .U 91003211 .S Br J Urol 9101; 66(3):245-7 .M Adult; Aged; Aged, 80 and over; Anesthesia, Local; Cystoscopy/*; Female; Human; Kidney Calculi/*TH; Lithotripsy/*; Male; Methods; Middle Age; Stents/*; Ureter. .T Flexible cystoscopy as an adjunct to extracorporeal shockwave lithotripsy. .P JOURNAL ARTICLE. .W Ancillary procedures associated with extracorporeal shockwave lithotripsy (ESWL) include placement and subsequent removal of double pigtail ureteric stents. A simple new technique has been developed for the insertion of these stents. Using the flexible cystoscope, the procedure is performed on an out-patient basis under local anaesthesia. Placement of the stents was successful in 30/34 patients and removal was successful in 14/14 patients. .A Mark SD; Gray JM; Wright WL. .I 274420 .U 91003212 .S Br J Urol 9101; 66(3):248-53 .M Aged; Carcinoma, Renal Cell/*SU; Female; Hemodialysis; Human; Kidney/AB; Kidney Neoplasms/*SU; Male; Middle Age; Nephrectomy/*/MT; Postoperative Complications/TH. .T Renal carcinoma in a solitary kidney. .P JOURNAL ARTICLE. .W We studied the clinical and pathological features of 26 patients with renal carcinoma of a solitary kidney, including 6 treated at this hospital. Four patients had a contracted kidney and 22 had previously undergone nephrectomy. Partial nephrectomy was performed in 16 patients, enucleation of the tumour in 5 and radical nephrectomy in 5 because of the size of the tumour. Ex vivo surgery was carried out in 4 patients. The duration of ischaemia ranged from 15 to 365 min but was longer in those who underwent ex vivo surgery (149 to 365 min). Of the 21 patients who underwent partial nephrectomy or enucleation, the serum creatinine level increased (greater than or equal to 2.0 mg/dl) post-operatively in 16 patients, of whom 9 required temporary haemodialysis. No recurrence has been noted in those who underwent partial nephrectomy, but 1 patient who underwent enucleation of the tumour developed a solitary pancreatic metastasis 2 years 6 months after surgery and was treated by a partial pancreatectomy. Kidney-preserving surgical procedures are considered to improve the quality of life, but careful follow-up is necessary. .A Gohji K; Kamidono S; Yamanaka N. .I 274421 .U 91003213 .S Br J Urol 9101; 66(3):254-6 .M Adult; Endoscopy; Female; Human; Male; Retrospective Studies; Stents/*; Ureteral Calculi/*TH. .T Use of the double pigtail stent in stone retrieval following unsuccessful ureteroscopy. .P JOURNAL ARTICLE. .W Insertion of a double pigtail stent is known to cause ureteric dilatation. We analysed the effect of an indwelling double pigtail stent on the success rate of calculus extraction by second ureteroscopy when the initial ureteroscopy fails. Over a 12-month period, a first ureteroscopy failed in 42 patients; 30 were then treated by ureteroscopy combined with a ureteric stent and 12 were treated without a ureteric stent. The group with an indwelling stent had a successful second ureteroscopy or spontaneously passed the calculus in 24 cases (84%) compared with 5 unstented cases (45%). Ureterolithotomy was necessary in 2 patients with a stent and 3 with no stent. It was concluded that following failed ureteroscopic manipulation of calculi, insertion of a double pigtail stent was associated with a higher subsequent success rate for removal of stone by ureteroscopy and a consequent lower rate of ureterolithotomy. .A Jones BJ; Ryan PC; Lyons O; Grainger R; McDermott TE; Butler MR. .I 274422 .U 91003215 .S Br J Urol 9101; 66(3):265-73 .M Bladder/IM/PA; Cystitis/*DI/ME/PA; Cystoscopy; Fluorescent Antibody Technique; IgM/AN; Periodic Acid-Schiff Reaction; Support, Non-U.S. Gov't. .T Immunofluorescent and histochemical staining confirm the identification of the many diseases called interstitial cystitis. .P JOURNAL ARTICLE. .W Interstitial cystitis comprises a complex of diseases typified by symptoms of pelvic pain. Functional complaints do not aid the clinician in determining loss of anatomical capacity. Histochemical staining with PAS-colloidal iron/Van Geison's counterstain offers improved diagnostic ability for the pathologist and correlates well with immunofluorescent findings. Four distinct diseases can be identified through immunofluorescent staining, indicating that each is the result of different responses of the urothelium and endothelium to injury. Loss of bladder capacity associated with these diseases can be expected with age, but immunofluorescent staining for IgM within the capillaries of the interstitium is a more sensitive predictor. .A Gillespie L; Said J; Sostrin S; Kleiwer K. .I 274423 .U 91003216 .S Br J Urol 9101; 66(3):274-8 .M Adult; Aged; Bladder/*PA; Cell Count; Cystitis/*CO/PA; Female; Human; Mast Cells/*; Middle Age; Urination Disorders/*ET. .T Do women with idiopathic sensory urgency have early interstitial cystitis? .P JOURNAL ARTICLE. .W Interstitial cystitis is rarely considered as a cause of urinary symptoms in referrals to gynaecology clinics. Recent concepts in the diagnosis of this condition mean that it is emerging as a much more common entity, with both early and late forms of the disease being described. Mast cell density in the detrusor muscle has been reported to be useful as a disease marker to substantiate the diagnosis of interstitial cystitis where no classical diagnostic features exist. We assessed mast cell counts in bladder biopsies from 27 women with idiopathic sensory urgency and 10 control patients about to undergo a colposuspension procedure for pure genuine stress incontinence; 30% of the study group had a clear increase in the detrusor muscle mast cell population (detrusor mastocytosis). No control patient showed such an increase. Early interstitial cystitis should be considered as a possible cause of lower urinary tract symptoms in patients with apparently idiopathic sensory urgency. .A Frazer MI; Haylen BT; Sissons M. .I 274424 .U 91003217 .S Br J Urol 9101; 66(3):279-80 .M Aged; Catheters, Indwelling; Human; Indicator Dilution Techniques; Male; Middle Age; Support, Non-U.S. Gov't; Urinary Catheterization/*ST; Urine/*. .T Assessment of residual urine in men following catheterisation [see comments] .P JOURNAL ARTICLE. .W There is a certain volume of urine left within the bladder which cannot be drained by a catheter. A dilutional method was used to calculate this residual volume in 15 men; 10 had acute retention secondary to benign prostatic hyperplasia and 5 had permanent indwelling catheters for neurogenic urinary incontinence. The mean catheterised residual volume was 98.53 ml for patients with acute retention and 14.48 ml for patients with long-term catheters. The explanation for higher post-catheterisation volumes in the acute retention group is probably multifactorial; bladder sacculation and diverticula, detrusor tone and reflux may all play a role. .A Purkiss SF. .I 274425 .U 91003218 .S Br J Urol 9101; 66(3):281-5 .M Antibodies, Monoclonal/*DU; Bladder Neoplasms/*PA; Carcinoma, Transitional Cell/*PA; Cell Division; Female; Human; Male; Middle Age; Neoplasm Staging; Prognosis. .T Cell cycling in bladder carcinoma determined by monoclonal antibody Ki67. .P JOURNAL ARTICLE. .W Current methods of predicting prognosis in transitional cell carcinoma of the bladder fail to provide consistently reliable information about future tumour behaviour. The monoclonal antibody Ki67 recognises an antigen present in actively dividing cells and Ki67 reactivity has been shown to correlate with conventional prognostic indicators in several tumours. In this study, Ki67 antibody was used to determine the proportions of cells undergoing active division in 26 transitional cell carcinomas of the bladder. The proportion of cells stained in muscle invasive tumours (12.3 +/- 5.4%) was significantly greater than in superficial tumours (4.3 +/- 1.9%) and poorly differentiated tumours showed significantly greater proportions of cells staining compared with well or moderately well differentiated tumours. These results show that Ki67 reactivity correlates with high tumour stage and poor differentiation. Ki67 staining provides an easy method of determining tumour cell turnover that might provide additional prognostic information. .A Mellon K; Neal DE; Robinson MC; Marsh C; Wright C. .I 274426 .U 91003219 .S Br J Urol 9101; 66(3):286-7 .M Administration, Intravesical; Adult; Age Factors; Antineoplastic Agents, Combined/*AD/TU; Bladder Neoplasms/*PC; BCG Vaccine/*AD/TU; Carcinoma, Transitional Cell/*PC; Human. .T Superficial bladder cancer in patients under 40 years of age. Efficacy of topical prophylaxis. .P JOURNAL ARTICLE. .W In patients under the age of 40 years with primary superficial bladder cancer the efficacy of adjuvant topical treatment was the same as in elderly patients (recurrences 23%, progression rate 8%). Patients should therefore be treated on the basis of stage and grade of the tumour regardless of their age. .A Flamm J. .I 274427 .U 91003221 .S Br J Urol 9101; 66(3):294-6 .M Adult; Case Report; Human; Male; Middle Age; Postoperative Complications/ET; Prostatectomy; Urethral Stricture/*CN/ET. .T Cobb's collar--a forgotten entity. .P JOURNAL ARTICLE. .W Cobb's collar or Moormann's ring is a stricture of the bulbar urethra which is largely unrecognised but has considerable relevance urologically as the site of congenital or post-instrumental strictures. The history, anatomy, embryology and surgical importance are reported. .A Cranston D; Davies AH; Smith JC. .I 274428 .U 91003222 .S Br J Urol 9101; 66(3):297-302 .M Adult; Aged; Bladder/*PP; Human; Middle Age; Quadriplegia/*CO/PP; Reflex, Abnormal; Stents/*; Urination Disorders/ET/*TH. .T Permanent external striated sphincter stents in patients with spinal injuries. .P JOURNAL ARTICLE. .W Nine patients with complete quadriplegia underwent external striated sphincter stenting with the Wallstent in place of an external striated sphincterotomy. Although suprapubic catheters were placed to provide an outlet should problems develop with the stent, they were successfully removed within 6 weeks in all but 1 patient. Complete bladder emptying with reduced voiding pressures was achieved, together with a significant reduction in the duration of hyper-reflexic contractions. Epithelialisation of the stent was almost complete within 3 months and intermittent catheterisation or endoscopy (and resection) is possible through the stent. Although this is a preliminary report of this new technique, it is hoped that sphincter stenting will provide a rapid, safe and effective method of treating high pressure hyper-reflexia and detrusor sphincter dyssynergia in quadriplegic patients. .A Shaw PJ; Milroy EJ; Timoney AG; el Din A; Mitchell N. .I 274429 .U 91003223 .S Br J Urol 9101; 66(3):303-5 .M Bladder/PP; Bladder Diseases/PP/*SU; Bladder Neck Obstruction/ET/PP; Human; Male; Prostatectomy/*; Prostatic Diseases/CO/SU; Urodynamics/*. .T Symptoms versus flow rates versus urodynamics in the selection of patients for prostatectomy. .P JOURNAL ARTICLE. .W Many prostatectomies are performed on the basis of symptoms alone; 39% of patients referred by their family doctors and 23% of patients who were on waiting lists for prostatectomy of other hospitals, but who had not undergone any urodynamic investigations, were found to be unobstructed on urodynamic criteria. A screening peak urinary flow rate of 12 ml/s or less was associated with urodynamic evidence of obstruction in 95% of cases; 35% of patients with symptoms of outflow obstruction and a flow rate greater than 12 ml/s were also found to be obstructed. One year post-operatively, 84% of patients who were selected for surgery on combined symptomatic and urodynamic criteria were pleased symptomatically with their result. The failure of detrusor instability to resolve following prostatectomy was associated with symptomatic failure of treatment. Residual obstruction was demonstrated in 5 patients who had undergone prostatectomy and were asymptomatic at this time. This study illustrates that objective measures are necessary in the assessment of patients prior to prostatectomy in order to select only patients who are obstructed. The importance of a screening flow rate is emphasised. All patients who underwent surgery had cystometric evidence of obstruction but the symptomatic results of surgery were no better than the results in patients who had been assessed according to non-urodynamic selection criteria. We have thus failed to identify a need for routine cystometry in the pre-operative assessment of these patients. Cystometry does, however, have a role in assessing patients with pre-operative flow rates greater than 12 ml/s and in those who remain symptomatic following prostatectomy. .A McLoughlin J; Gill KP; Abel PD; Williams G. .I 274430 .U 91003224 .S Br J Urol 9101; 66(3):306-11 .M Adenocarcinoma/*PA; Adult; Aged; Aged, 80 and over; Follow-Up Studies; Human; Male; Middle Age; Precancerous Conditions/*PA; Prognosis; Prostatic Neoplasms/*PA; Retrospective Studies. .T Pathological classification and follow-up of prostatic lesions initially diagnosed as "suspicious of malignancy". .P JOURNAL ARTICLE. .W Sections from a series of prostatic specimens (n = 44) in which the initial diagnosis implied a suspicion of malignancy were reviewed and the patients followed up (group 1). The aim was to categorise the morphological appearances according to current criteria and to determine the natural history of any pre-malignant lesions within this group. A "control" series of patients (n = 40) in whom the primary diagnosis was benign were also reviewed and their course followed (group 2). The heterogeneity of the abnormalities in group 1 was striking. Of the 44 cases, pre-malignant lesions were seen in 8, microinvasive adenocarcinoma in 11 and lesions not now considered pre-malignant in the remaining 25. None of the 8 patients with pre-malignant lesions developed clinical evidence of carcinoma over a follow-up period of 8 to 12 years. In contrast, 3 of the 11 diagnosed on review as having microscopic invasive adenocarcinoma developed clinically evident tumour within 5 years of surgery. Of the 25 patients whose prostatic lesions were considered benign, 2 developed carcinoma 12 and 13 years after surgery. Only 1 of the 40 patients in group 2 had a pre-malignant lesion and he did not develop tumour within 10 years. However, adenocarcinoma was diagnosed incidentally in 1 patient 3 years after surgery. It was concluded that there is a need to standardise interpretation and reporting of pre-malignant lesions and microscopic foci of adenocarcinoma in the prostate. The limited results on the course of pre-malignant lesions diagnosed incidentally in patients over 60 years of age do not indicate that follow-up would have prompted the early diagnosis of invasive disease. .A Keane PF; Ilesley IC; O'Donoghue PN; Parkinson MC. .I 274431 .U 91003225 .S Br J Urol 9101; 66(3):312-4 .M Adult; Aged; Granuloma/*DI/PA; Human; Male; Middle Age; Orchitis/*DI/PA. .T Granulomatous orchitis. Review of 15 cases. .P JOURNAL ARTICLE. .W Granulomatous orchitis is a rare lesion of the testis which can clinically simulate malignancy. The clinical, radiological and pathological features of 15 patients are presented and discussed. .A Aitchison M; Mufti GR; Farrell J; Paterson PJ; Scott R. .I 274432 .U 91003227 .S Br J Urol 9101; 66(3):318-21 .M Africa, Southern; Antibiotics/TU; Circumcision/*AE; Culture/*; Human; Male; Penis/*IN/SU; Wound Infection/DT/*ET. .T Ritual circumcision (Umkhwetha) amongst the Xhosa of the Ciskei. .P JOURNAL ARTICLE. .W The Umkhwetha is an ancient custom of ritual circumcision still practised by the Xhosa people of Southern Africa. In 45 consecutive youths who required hospital admission the mortality rate was 9%. The complication seen over the years are reviewed and their management discussed. .A Crowley IP; Kesner KM. .I 274433 .U 91003229 .S Br J Urol 9101; 66(3):323 .M Case Report; Child, Preschool; Human; Male; Polyps/*; Urethral Neoplasms/*. .T Anterior urethral polyp in a child. .P JOURNAL ARTICLE. .A Azmy AF. .I 274434 .U 91003230 .S Br J Urol 9101; 66(3):323-4 .M Aged; Case Report; Human; Lipomatosis/*PA; Male; Ureteral Neoplasms/*PA. .T Lipomatosis of the ureter. .P JOURNAL ARTICLE. .A Thorpe AC; Martin JE; Jenkins BJ. .I 274435 .U 91003231 .S Br J Urol 9101; 66(3):324-5 .M Adult; Case Report; Dysgerminoma/*PA; Epididymis/*PA; Human; Male; Testicular Neoplasms/*PA. .T Juxtatesticular seminoma. .P JOURNAL ARTICLE. .A Dichmann O; Engel U; Jensen DB; Bilde T. .I 274436 .U 91003232 .S Br J Urol 9101; 66(3):325-6 .M Aged; Aged, 80 and over; Case Report; Epididymis/*; Human; Male; Prostatic Neoplasms/*PA; Testicular Neoplasms/*SC. .T Epididymal metastasis from prostatic carcinoma. .P JOURNAL ARTICLE. .A Sneiders A; Heller JE. .I 274437 .U 91003233 .S Br J Urol 9101; 66(3):326 .M Aged; Aged, 80 and over; Case Report; Cystadenoma/*CO; Cysts/*CN; Human; Male; Pelvic Neoplasms/*CO; Urinary Retention/*ET. .T Recent change in a tailgut cyst presenting as urinary retention. .P JOURNAL ARTICLE. .A Stephenson BM; Bartlet M; Nirula R; Evans AG; Rees AM. .I 274438 .U 91003234 .S Br J Urol 9101; 66(3):327 .M Aged; Aged, 80 and over; Case Report; Female; Human; Kidney Calculi/*TH; Proteus Infections/DT; Trimethoprim/*TU; Urinary Tract Infections/DT. .T Disappearing staghorns [see comments] .P JOURNAL ARTICLE. .A Griffith-Jones MD. .I 274439 .U 91003235 .S Br J Urol 9101; 66(3):328 .M Foreign-Body Migration/TH; Human; Nephrostomy, Percutaneous/*; Stents/*; Ureter/*. .T Minimally invasive removal of retained ureteric stents. .P JOURNAL ARTICLE. .A White PG; Evans C. .I 274440 .U 91003236 .S Br J Urol 9101; 66(3):329 .M Bladder/*SU; Cystoscopy/*; Human; Suture Techniques/*; Urinary Incontinence, Stress/SU; Video Recording/*. .T The endoscopic video camera as an aid to the Stamey procedure. .P JOURNAL ARTICLE. .A Harrison SC; Abrams PH. .I 274441 .U 91003237 .S Br J Urol 9101; 66(3):330-1 .M Bladder Neoplasms/*RT; Human. .T Re: The fate of G3pT1 bladder cancer [letter; comment] .P COMMENT; LETTER. .A Harland SJ. .I 274442 .U 91003239 .S Br J Surg 9101; 77(9):1000-3 .M Adolescence; Adult; Comparative Study; Female; Human; Male; Middle Age; Pancreatic Neoplasms/*PA/RA/SU/US; Retrospective Studies; Support, Non-U.S. Gov't; Tomography, X-Ray Computed. .T Papillary cystic neoplasm of the pancreas: radiological and pathological characteristics in 11 cases. .P JOURNAL ARTICLE. .W Clinical charts, radiological features, macroscopic and microscopic findings, and clinical follow-up data were retrospectively reviewed in 11 patients with papillary cystic neoplasm of the pancreas (PCNP). The patients were nine women and two men, aged from 13 to 51 years with a mean age of 25 years. The greatest diameter of the PCNPs ranged from 2.5 cm to 14.0 cm with a mean size of 7.5 cm. Six tumours were located in the tail of the pancreas, two in the body and three in the head. Most patients complained of abdominal pain or a mass. Ultrasonographic and/or computed tomography findings showed five solid, four mixed (solid and cystic) and two cystic types of tumour. Angiographically, PCNP was either a hypovascular or mild hypervascular mass with a displacement of the surrounding vessels. No vascular encasement was seen. Macroscopically all 11 tumours consisted of a well defined solid mass with degenerative change of various widths, including haemorrhage, necrosis or dystrophic calcification, and were represented by three radiological types of PCNP. The 11 patients with PCNP survived for from 3 to 253 months after curative resection without any signs of local recurrence or remote metastasis. PCNP usually affects the distal portion of the pancreas of young women. Despite its huge size, PCNP should be explored with aggressive surgical intent because of the inherently good prognosis. .A Yamaguchi K; Hirakata R; Kitamura K. .I 274443 .U 91003240 .S Br J Surg 9101; 77(9):1004-6 .M Adolescence; Adult; Aged; Aged, 80 and over; Comparative Study; Duodenal Ulcer/CO/*SU; Emergencies; Female; Gastrectomy; Human; Male; Middle Age; Peptic Ulcer Hemorrhage/*SU; Postoperative Complications/ET; Pylorus/SU; Recurrence; Vagotomy. .T Choice of emergency operative procedure for bleeding duodenal ulcer [see comments] .P JOURNAL ARTICLE. .W In a consecutive series of 201 emergency operations in patients with bleeding duodenal ulcer the size of the ulcer was the only factor that showed a significant correlation with the procedure chosen. Vagotomy, pyloroplasty and underrunning of the bleeding point was performed in 101 cases with ten deaths (10 per cent), partial (Billroth II) gastrectomy in 81 cases with ten deaths (12 per cent), and vagotomy and antrectomy in 16 cases with one death (6 per cent). A patient was more likely to be treated by partial gastrectomy if a giant ulcer with an internal diameter of greater than or equal to 2 cm was found. The results suggest that while vagotomy and pyloroplasty, combined with a direct attack on the bleeding point or excision of an anterior ulcer is an acceptable standard emergency operation for bleeding duodenal ulcer, gastric resection proved to be a satisfactory alternative procedure and should be considered in the technically difficult case with a very large ulcer. A giant ulcer was present in 37 per cent of cases coming to surgery. .A Hunt PS; McIntyre RL. .I 274444 .U 91003241 .S Br J Surg 9101; 77(9):1006 .M Adult; Aged; Duodenal Ulcer/CO; Female; Human; Male; Middle Age; Peptic Ulcer Perforation/*SU; Peritoneoscopy/*; Postoperative Complications/PC; Stomach Ulcer/CO. .T Laparoscopic treatment of perforated peptic ulcer. .P JOURNAL ARTICLE. .A Mouret P; Francois Y; Vignal J; Barth X; Lombard-Platet R. .I 274445 .U 91003242 .S Br J Surg 9101; 77(9):1007-9 .M Adult; Chronic Disease; Comparative Study; Diarrhea/ET; Dumping Syndrome/ET; Duodenal Ulcer/*SU; Female; Gastric Acid/SE; Gastric Emptying/PH; Human; Male; Middle Age; Myocardial Infarction/ET; Postoperative Complications/ET; Prospective Studies; Pylorus/SU; Recurrence; Vagotomy, Truncal. .T Anterior lesser curve seromyotomy and posterior truncal vagotomy versus truncal vagotomy and pyloroplasty in the treatment of chronic duodenal ulcer. .P CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL. .W In a prospective randomized controlled clinical trial, anterior lesser curve seromyotomy with posterior truncal vagotomy (AMPT, n = 77) has been compared with truncal vagotomy and pyloroplasty (TVP, n = 69) in 146 patients with chronic duodenal ulcer with a mean duration of symptoms of 7 years. The mean follow-up time was 4.5 years with a range of 2-7 years. One elderly patient died from a myocardial infarction in the TVP group. Acid secretory inhibition in response to insulin and pentagastrin stimuli was equal in both groups, indicating a similar degree of vagal denervation. Recurrent ulcers were more common after AMPT (five) than TVP (two) (P = 0.29, n.s.). Dumping and diarrhoea were significantly commoner (P less than 0.001) after TVP, with 31 instances as opposed to eight with AMPT. The mean operating time was increased by 6 min when AMPT was performed rather than TVP. The results of this study have shown that AMPT is associated with a lower incidence of dumping and diarrhoea and achieves better overall Visick grading. However, continued monitoring is required to assess the long-term incidence of recurrent ulceration after this procedure. .A Taylor TV; Lythgoe JP; McFarland JB; Gilmore IT; Thomas PE; Ferguson GH. .I 274446 .U 91003243 .S Br J Surg 9101; 77(9):1010-3 .M Adult; Aged; Aged, 80 and over; Antigens, Tumor-Associated, Carbohydrate/*AN; Carcinoembryonic Antigen/AN; Comparative Study; Female; Human; Lymphatic Metastasis; Male; Middle Age; Neoplasm Staging; Stomach Neoplasms/*IM/PA; Tumor Markers, Biological/*BL. .T CA72-4: a new tumour marker for gastric cancer. .P JOURNAL ARTICLE. .W To date, tumour markers for gastric cancer have proved unreliable. In this study the value of a new serum marker, CA72-4, was compared with the serum activities of carcinoembryonic antigen (CEA) and CA19-9 in a consecutive series of patients with gastric cancer. The results show that the CA72-4 assay is significantly better at separating stage I and II disease from normal controls (P less than 0.01) than CEA (n.s.) or CA19-9 (n.s.). CA72-4 also gave better differentiation between patients with positive and negative nodes (P less than 0.01) and between those who were serosa positive and negative (P less than 0.01). CEA differentiated between patients with positive and negative nodes (P less than 0.05) but CA19-9 could not. CA19-9 and CEA could not discriminate between patients who were serosa positive and negative. In this study, at a specificity of 95 per cent, the sensitivities of CEA, CA19-9 and CA72-4 were 0.25, 0.41 and 0.94 respectively. These preliminary findings indicate that CA72-4 is a reliable tumour marker of disease stage and activity in gastric cancer. Further longitudinal studies are required for full evaluation of its clinical utility. .A Byrne DJ; Browning MC; Cuschieri A. .I 274447 .U 91003244 .S Br J Surg 9101; 77(9):1013-4 .M Adult; Aged; Aged, 80 and over; Carcinoid Tumor/*SU; Female; Human; Male; Middle Age; Prognosis; Stomach Neoplasms/*SU. .T Primary gastric carcinoids: a view on management [see comments] .P JOURNAL ARTICLE. .A Davies MG; O'Dowd G; McEntee GP; Hennessy TP. .I 274448 .U 91003245 .S Br J Surg 9101; 77(9):1015-7 .M Adenocarcinoma/SU; Adipose Tissue/CH; Adult; Aged; Body Composition; Body Weight; Caloric Intake; Feces/CH; Female; Gastrectomy/*; Human; Lymphoma/SU; Male; Middle Age; Nutrition Disorders/*ET; Postoperative Complications/*ET; Proteins/AN; Stomach Neoplasms/SU. .T Failure of nutritional recovery after total gastrectomy. .P JOURNAL ARTICLE. .W Malnutrition is reported to be an inevitable consequence of total gastrectomy, although there are few data to support this contention. Six patients of median age 63 years underwent total gastrectomy for malignancy. At follow-up (median 45 months, range 25-60 months) each patient was clinically tumour-free and underwent dietary assessment, faecal fat and nitrogen measurement and routine haematological testing. Protein and fat stores, measured by neutron activation analysis and the tritiated water dilution technique, were compared with the same measurements made before operation and with predicted values. Mean (s.d.) dietary intake (2224(381) kcal day-1 and 81(15)g protein day-1) met the patients' estimated requirements. Mean(s.d.) serum albumin and faecal nitrogen values were normal but there was notable steatorrhoea (21(17) g day-1). Body composition measurements revealed profound deficiencies of body-weight (P less than 0.02), protein (P less than 0.01) and fat (P less than 0.02) before operation which were not corrected by an apparently curative total gastrectomy (P less than 0.05), although further deterioration was prevented. .A Curran FT; Hill GL. .I 274449 .U 91003247 .S Br J Surg 9101; 77(9):1020-3 .M Adenocarcinoma/*DT/PA/RT/SU; Antineoplastic Agents, Combined/*TU; Cardia; Cisplatin/AD; Combined Modality Therapy; Fluorouracil/AD; Human; Palliative Treatment; Prognosis; Stomach Neoplasms/*DT/PA/RT/SU; Support, Non-U.S. Gov't. .T Treatment of adenocarcinoma of the cardia with synchronous chemotherapy and radiotherapy. .P CLINICAL TRIAL; JOURNAL ARTICLE. .W Twenty-nine evaluable patients with adenocarcinoma of the cardia were treated with synchronously administered chemotherapy (two cycles of 5-fluouracil and cisplatin and 30-36 Gy of radiation to determine whether these tumours are responsive to such treatment. Complete regression of tumour was observed endoscopically in 19 patients, and partial regression in four. Fourteen patients had their tumours resected and in six no microscopic tumour was found in the specimen. Nine patients received additional radiotherapy to a total dose of 54-60 Gy instead of surgery. Tumour response was associated with rapid reversal of dysphagia. Only one patient required subsequent intervention for relief of dysphagia due to fibrous stricture. Enhanced survival was associated with a complete endoscopic response to initial chemotherapy and radiotherapy, and a tumour of less than 5 cm in length. The median survival of responding patients was 15 months. Synchronous chemotherapy and radiotherapy was of major palliative benefit in this series and merits further evaluation. .A Gill PG; Jamieson GG; Denham J; Devitt PG; Ahmad A; Yeoh E; Jones AM. .I 274450 .U 91003248 .S Br J Surg 9101; 77(9):1023-4 .M Adenocarcinoma/CO; Adult; Aged; Aged, 80 and over; Duodenal Neoplasms/CO; Duodenal Ulcer/*CO; Female; Human; Male; Middle Age; Prospective Studies; Pyloric Stenosis/*ET; Stomach Neoplasms/*CO/DI. .T Gastric outlet obstruction now predicts malignancy. .P JOURNAL ARTICLE. .A Johnson CD; Ellis H. .I 274451 .U 91003249 .S Br J Surg 9101; 77(9):1025-9 .M Aged; Anastomosis, Roux-en-Y/*; Eating/PH; Fasting/PH; Female; Gastrectomy/*; Gastrointestinal Motility/*PH; Human; Jejunum/*SU; Male; Manometry; Middle Age; Postoperative Care; Stomach Neoplasms/PP/*SU. .T Manometric evaluation of jejunal limb after total gastrectomy and Roux-Orr anastomosis for gastric cancer. .P JOURNAL ARTICLE. .W Total gastrectomy with Roux-Orr anastomosis is frequently performed for gastric cancer. Since intestinal motility of the Roux limb has never been evaluated after this operation, pressure activity was investigated in the Roux limb of ten patients (aged 51-77 years) who had undergone total gastrectomy and Roux-Orr reconstruction. Investigations were carried out during a 6-h fast and 3 h after a 605 kcal mixed meal. During fasting only two patients had activity fronts and these were abnormal. All ten patients displayed non-propagating bursts of contractions and three had discrete clustered contractions and high amplitude jejunal contractions. The fed state was characterized by a severely reduced motor activity pattern and other abnormalities. Total gastrectomy with Roux-Orr anastomoses provokes a relatively severe disturbance in intestinal activity. .A Bassotti G; Gulla P; Betti C; Whitehead WE; Morelli A. .I 274452 .U 91003251 .S Br J Surg 9101; 77(9):1030-5 .M Anastomosis, Surgical/*MT; Animal; Anus/SU; Colectomy/*MT; Defecation/PH; Dogs; Female; Gastrointestinal Transit/PH; Ileum/PH/*SU; Muscle, Smooth/SU; Postoperative Complications/PC; Pressure; Rectum/*SU. .T Single lumen ileum with myectomy: a possible alternative to the pelvic reservoir in restorative proctocolectomy. .P JOURNAL ARTICLE. .W An alternative procedure to construction of a pelvic ileal reservoir was assessed which avoids the need for a pouch, while providing an adequate rectal substitute and good continence. Thirty-six female adult beagles were allotted randomly to undergo total colectomy with (a) ileo-anal anastomosis alone, (b) ileo-anal anastomosis with two 15 cm myectomies, (c) ileo-anal anastomosis and myectomy with an ileo-ileal valve, or (d) ileo-anal anastomosis with a duplicated J pouch. The animals were studied before operation and at 4-weekly intervals for 20 weeks after operation. Mortality rates were similar. Ileal compliance was increased significantly by myectomy from 0.64 ml/mmHg (median, interquartile range 0.49-0.78) after ileo-anal anastomosis alone to 1.65 mmHg (1.16-1.93), P less than 0.01, an increase which was maintained. Ileal capacity was also increased both by myectomy and by the J pouch: ileo-anal anastomosis = 85 ml (75-100 ml), ileo-anal anastomosis and myectomy = 139 ml (116-156 ml), ileo-anal anastomosis and myectomy and ileo-ileal valve = 125 ml (range 85-145 ml), ileo-anal anastomosis and J pouch = 130 ml (range 75-165 ml) (P less than 0.01). Bowel function in the other three groups was markedly superior to ileo-anal anastomosis alone. Mean transit time was significantly less after ileo-anal anastomosis, 5.2 h (2.6-8.2 h) than after both ileo-anal anastomosis and myectomy, 10.5 h (9.6-13.9 h), P less than 0.05 and ileo-anal anastomosis and J pouch, 11.0 h (8.4-13.0 h), P less than 0.05, but addition of an ileo-ileal valve did not produce a further increase in transit time, 12.9 h (range 10.5-14.5 h), P = n.s.. Myectomy of single lumen ileum may be a useful alternative to a pelvic ileal reservoir in restorative proctocolectomy. .A Sagar PM; Holdsworth PJ; King RF; Salter G; Johnston D. .I 274453 .U 91003252 .S Br J Surg 9101; 77(9):1036-8 .M Abscess/CO/SU; Adult; Aged; Aged, 80 and over; Anastomosis, Surgical; Bladder Fistula/CO/SU; Diverticulosis, Colonic/CO/*SU; Female; Human; Intestinal Fistula/CO/SU; Male; Middle Age; Postoperative Complications/ET; Sigmoid/SU; Sigmoid Diseases/*SU. .T Elective resection for diverticular disease of the sigmoid colon. .P JOURNAL ARTICLE. .W From 1966 to 1987, 177 consecutive patients were operated on electively for diverticular disease of the sigmoid colon. The indications for surgery were: colovesical fistula (n = 12), suspicion of residual abscess (n = 39), two or more previous attacks of acute inflammation (n = 52), chronic symptoms (n = 72) and suspicion of carcinoma (n = 2). An abscess was found at operation in 76 patients (43 per cent) and this was extracolic with local peritonitis in 52 patients (29 per cent). An unsuspected abscess was found in 25 of the 72 patients operated on for chronic symptoms. Colonic resection with primary anastomosis was performed in 95 per cent of the 177 patients and in 94 per cent of those 52 patients with an extracolic abscess. There were no postoperative deaths and no clinical anastomotic leakages. Long-term results were very good in 85 per cent of the 177 patients and in 82 per cent of the 72 patients operated on for chronic symptoms. The results of this series suggest that a one-stage procedure can be safely performed with some technical precautions in most patients operated on electively for diverticular disease, even if an extracolic abscess is found. The good long-term results in patients operated on for chronic symptoms suggest that such symptoms should be taken into account with respect to surgical indications. .A Moreaux J; Vons C. .I 274454 .U 91003253 .S Br J Surg 9101; 77(9):1039-40 .M Adolescence; Adult; Anus/PP; Fecal Incontinence/PP/*SU; Female; Human; Male; Middle Age; Muscles/*TR; Physical Therapy; Postoperative Care; Pressure; Thigh. .T Gracilis muscle transposition for faecal incontinence. .P JOURNAL ARTICLE. .W Transposition of the gracilis muscle for faecal incontinence was performed in 13 patients. Six gained satisfactory continence, four were improved, two did not benefit from the operation and one patient died from intercurrent disease before closure of a pre-existing colostomy. Anal manometry compared with a control group showed no alteration in resting and pressure at a median of 35 mmHg (range 5-63 mmHg), whereas maximum squeeze pressure increased from a median of 38 mmHg (range 5-79 mmHg) to 59 mmHg (range 10-143 mmHg) (P = 0.041) which was, however, significantly lower than 130 mmHg (range 81-236 mmHg) in the control group. All patients who benefited from the operation had an increase in maximum squeeze pressure. The ability to retain a viscous fluid in the rectum was measured in seven patients, four of whom had gained satisfactory continence and three of whom had improved continence. They were able to retain a median volume of 200 ml (range 50-225 ml) without leakage compared with 325 ml (range 250-400 ml) in the control group. These patients could retain the maximum amount of viscous fluid for 5-8 min, whereas all control subjects could do so for more than 15 min. It is concluded that, although gracilis transposition never results in normal continence, acceptable continence may be achieved in selected patients provided careful attention is paid to the technical details of the procedure and provided that systematic postoperative exercises are performed. .A Christiansen J; Sorensen M; Rasmussen OO. .I 274455 .U 91003254 .S Br J Surg 9101; 77(9):1041-2 .M Acute Disease; Arm/*BS; Attitude of Health Personnel; Great Britain; Hemorrhage/ET; Human; Ireland; Ischemia/*DT; Leg/*BS; Streptokinase/TU; Thromboembolism/DT; Thrombolytic Therapy/AE/*UT. .T Survey of the use of thrombolysis for acute limb ischaemia in the UK and Ireland. .P JOURNAL ARTICLE. .W A total of 156 vascular surgeons from the UK and Ireland responded to a postal questionnaire on the use of thrombolysis in acute limb ischaemia. Almost half had used thrombolysis in the previous 12 months. Low dose intra-arterial streptokinase (89 per cent) was the regimen most frequently used, but 33 per cent had used intravenous streptokinase. Detailed results for 103 patients (limb salvage rate 60 per cent, amputation rate 35 per cent, mortality rate 5 per cent) were similar to those of previously published reports. Complications in most series were infrequent, but in the entire survey there were six bleeding-related deaths and one death from anaphylaxis. A total of 67 per cent of surgeons with working experience indicated that selected patients with acute arterial thromboses were most suitable for thrombolysis, particularly if there was no neurological deficit and no run-off for surgical bypass. Distal or late emboli and graft occlusions were regarded as appropriate by some surgeons. This study demonstrated that many vascular surgeons currently use thrombolysis, although sparingly and in selected cases. Patients with acute limb ischaemia should be managed by experienced vascular surgeons who are aware of the new therapeutic alternatives, an ideal supported by almost three-quarters of respondents to this survey. .A Earnshaw JJ; Shaw JF. .I 274456 .U 91003255 .S Br J Surg 9101; 77(9):1043-5 .M Adult; Blood Flow Velocity; Blood Vessels/IR; Female; Hand/*BS; Human; Intercostal Nerves/*SU; Ischemia/PP/*SU; Male; Middle Age; Raynaud's Disease/SU; Reoperation; Sympathectomy/*. .T Resympathectomy of the upper extremity. .P JOURNAL ARTICLE. .W Resympathectomy was performed in 27 patients (eight bilaterally) with ischaemic hand phenomena. An extended operative technique, resecting parts of the second and third intercostal nerves and their surrounding tissue, was used. In all 35 procedures the posterior extrapleural approach was used. Follow-up was from 3 to 12 years. Only the sympathetic ganglia had been removed during the previous surgery by the axillary approach (67 per cent of these patients had had a transient response for between 6 months and 2 years; 33 per cent had had no response at all). A direct subjective improvement was seen after 27 of the 35 reoperations (77 per cent). In 14 patients continuous wave Doppler ultrasound studies were available and showed a significant increase in peak forward frequency after operation (P less than 0.001). From these data it may be concluded that it is possible to obtain a resympathectomy effect, but reoperation should be reserved for special cases for whom survival of digits is essential. .A van Rhede van der Kloot EJ; Jorning PJ. .I 274457 .U 91003258 .S Br J Surg 9101; 77(9):1055-9 .M Adult; Aged; Anesthesia, General/*; Human; Intraoperative Period; Leg/*BS; Middle Age; Postoperative Complications/ET; Sodium Chloride/PD; Support, Non-U.S. Gov't; Surgery, Operative/*; Thrombophlebitis/ET/US; Vasodilation/DE/*PH; Veins/AH/*PP/US. .T Venous stasis and vein lumen changes during surgery [see comments] .P JOURNAL ARTICLE. .W The mechanisms underlying the development of postoperative deep vein thrombosis remain to be fully elucidated. Previous studies have suggested that peroperative venous distension may be a factor associated with venous thromboembolism. In this study we have obtained high resolution ultrasound images of gastrocnemius and posterior tibial veins in 62 patients undergoing a range of general surgical procedures. From these we determined the changes in vein diameter occurring during the operative procedures, in response to induction of anaesthesia, and after completion of surgery. Veins showed no evidence of dilatation in response to the induction of anaesthesia, but by the end of the operative procedure showed distension of 22-28 per cent. Distension was most prominent in the gastrocnemius veins, and lesser distension was observed in the posterior tibial veins. In a series of patients who received an infusion of 1 litre of saline in addition to basal requirements, distension was 57 per cent compared with 22 per cent in the corresponding control group. Intraoperative venous distension is associated with factors that lead to deep vein thrombosis and may be involved in the mechanisms which result in the commencement of deep vein thrombosis. .A Coleridge-Smith PD; Hasty JH; Scurr JH. .I 274458 .U 91003259 .S Br J Surg 9101; 77(9):1060-1 .M Anus Neoplasms/*SU; Case Report; Cicatrix/PC; Condylomata Acuminata/*SU; Human; Male; Methods; Middle Age; Postoperative Complications/PC; Skin Transplantation/IS; Surgical Instruments/*. .T Use of skin graft knife in the treatment of giant perianal condyloma acuminatum. .P JOURNAL ARTICLE. .A Notaras MJ; Murray WJ; Manek S. .I 274459 .U 91003260 .S Br J Surg 9101; 77(9):1062 .M Deglutition Disorders/TH; Gastroscopy/MT; Gastrostomy/*MT; Human; Skin/SU. .T Percutaneous gastrostomy: an alternative endoscopic approach. .P JOURNAL ARTICLE. .A Iftikhar SY; McIntyre AS. .I 274460 .U 91003261 .S Br J Surg 9101; 77(9):1063-5 .M Colonic Neoplasms/DI/PC/*TH; Colonoscopy; Diet; Human; Occult Blood; Rectal Neoplasms/DI/PC/*TH; Risk Factors. .T Cancer of the colon and rectum. .P CONSENSUS DEVELOPMENT CONFERENCE; JOURNAL ARTICLE; REVIEW. .I 274461 .U 91003262 .S Br J Surg 9101; 77(9):1071-2 .M Diffusion; Fibrin; Human; Oxygen Consumption; Skin/ME; Varicose Ulcer/*ET. .T Aetiology of venous ulceration [letter; comment] .P COMMENT; LETTER. .I 274462 .U 91003263 .S Br J Surg 9101; 77(9):1073 .M Aged; Aged, 80 and over; Cholecystectomy; Common Bile Duct Calculi/*SU; Human; Postoperative Complications/ET; Sphincterotomy, Transhepatic/*. .T Endoscopic sphincterotomy for bile duct stones in patients with intact gallbladders [letter; comment] .P COMMENT; LETTER. .A Templeton JL; Bornman PC. .I 274463 .U 91003264 .S Br J Surg 9101; 77(9):1073 .M Biliary Fistula/SU; Echinococcosis, Hepatic/*SU; Human; Postoperative Complications/SU; Sphincterotomy, Transhepatic/*. .T Endoscopic sphincterotomy in hepatic hydatid disease open to the biliary tree [letter; comment] .P COMMENT; LETTER. .A Akoglu M; Hilmioglu F; Balay AR; Sahin B; Davidson BR. .I 274464 .U 91003265 .S Br J Surg 9101; 77(9):1074 .M Cholangiography/*; Cholecystectomy/*; Common Bile Duct Calculi/RA; Human; Intraoperative Care. .T Operative cholangiography in elective cholecystectomy [letter; comment] .P COMMENT; LETTER. .A Coleman J; Paul A; Spangenberger W; Klein J; Troidl H. .I 274465 .U 91003266 .S Br J Surg 9101; 77(9):1074 .M Burns, Chemical/*TH; Case Report; Child, Preschool; Esophageal Perforation/*TH; Human; Intubation, Gastrointestinal/*; Male; Mediastinitis/CO; Pneumothorax/CO. .T T tube intubation in the management of oesophageal fistula [letter; comment] .P COMMENT; LETTER. .A Zer M; Freud E. .I 274466 .U 91003267 .S Br J Surg 9101; 77(9):1074 .M Animal; Education, Medical, Undergraduate/*; Intestine, Small/SU; Surgery/*ED; Swine. .T Use of fresh porcine bowel in surgical training [letter] .P LETTER. .A Hoffmann J; Munksdorf M; Fischer AB. .I 274467 .U 91003268 .S Br J Surg 9101; 77(9):1075 .M Colorectal Neoplasms/*DT; Fluorouracil/*TU; Human; Time Factors. .T A randomized controlled trial of oral 5-FU versus placebo in colorectal cancer: results of 10 years observation time [letter] .P CLINICAL TRIAL; LETTER; RANDOMIZED CONTROLLED TRIAL. .A Hafstrom L. .I 274468 .U 91003269 .S Br J Surg 9101; 77(9):1075 .M Cholecystectomy/*; Common Bile Duct/SU; Drainage; Human; Intubation/*AE; Postoperative Complications/*TH. .T Bile leakage after removal of T tubes from the common bile duct [letter] .P LETTER. .A Placer Galan C; Colina Alonso A. .I 274469 .U 91003271 .S Br J Surg 9101; 77(9):963 .M Endoscopy, Digestive System; Esophageal and Gastric Varices/*TH; Fibrosis; Gastrointestinal Hemorrhage/*TH; Human; Portal Vein/PA; Sclerotherapy/*AE; Splenic Vein/PA. .T Endoscopic sclerotherapy: the far and near effects [editorial] .P EDITORIAL. .A Chaudhary A; Tatke M; Aranya RC. .I 274470 .U 91003272 .S Br J Surg 9101; 77(9):964-7 .M Blood Transfusion/AE; Female; Human; Malaria/*CO/TM; Postoperative Complications/PC; Recurrence; Spleen/*SU; Splenectomy/AE; Splenic Rupture/SU; Splenomegaly/SU. .T Surgical aspects of malaria. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W The spread of drug-resistant organisms and increased international travel makes malaria a disorder of ever-increasing importance. This report reviews those aspects of malaria of surgical relevance. The importance of the spleen in host defence against malaria and other infections makes splenic preservation desirable whenever possible after rupture of the spleen. Tropical splenomegaly is caused by an abnormal immune response to malaria and is best managed medically. Careful selection of blood donors is essential to prevent transfusion malaria, and routine antimalarial prophylaxis is indicated for blood recipients in many endemic areas. The risk of postoperative malaria may justify chemoprophylaxis in certain patients. .A Gibney EJ. .I 274471 .U 91003273 .S Br J Surg 9101; 77(9):968-74 .M Duodenum/*SU; Gastric Emptying/PH; Gastrointestinal Motility/PH; Human; Marginal Ulcer/PC; Pancreatectomy/*/MT; Pancreatitis/SU; Postoperative Complications/PC. .T Pylorus preserving pancreatoduodenectomy: an overview. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Pylorus preserving pancreatoduodenectomy (PPPD) was reintroduced 12 years ago. Since that time, over 400 patients have undergone PPPD with approximately 41 per cent having chronic pancreatitis and 54 per cent having pancreatic and other periampullary malignancies. Reported 5-year survivals in this latter group have been comparable to those achieved by the classic Whipple procedure. The postoperative mortality rate in 339 reported patients has been 3.8 per cent. Postoperative morbidity, including delayed gastric emptying, has been similar to that of the classic Whipple operation. However, PPPD has been associated with fewer late problems with dumping, diarrhoea, delayed gastric emptying (8.6 per cent), and marginal ulceration (3.6 per cent). Moreover, most patients undergoing PPPD have been able to return to their preoperative and preillness weight. The additional advantage of decreased operative time makes PPPD an attractive alternative to the classic pancreatoduodenectomy. .A Grace PA; Pitt HA; Longmire WP. .I 274472 .U 91003274 .S Br J Surg 9101; 77(9):975-82 .M Choledochostomy/IS/*MT; Common Bile Duct Calculi/*SU; Endoscopy; Human; Intraoperative Care; Postoperative Complications/ET. .T Operative choledochoscopy: common bile duct exploration is incomplete without it. .P JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC. .W This paper reviews the reported experience of operative choledochoscopy. Development of choledochoscopes to the currently available rigid and flexible instruments is described. The collected results of both rigid and flexible choledochoscopy are reported. Retained stones occurred in 97 of 2712 stone-positive explorations with the rigid choledochoscope (3.6 per cent) and in 35 of 1726 stone-positive explorations with the flexible choledochoscope (2.0 per cent). Choledochoscopy should now be a mandatory part of common bile duct exploration. .A Motson RW; Wetter LA. .I 274473 .U 91003275 .S Br J Surg 9101; 77(9):983-7 .M Adolescence; Adult; Aged; Child; Child, Preschool; Cholangioma/SU; Female; Hepatoma/PA/SU; Human; Liver Cirrhosis/CO; Liver Neoplasms/CO/PA/*SU; Liver Transplantation/*; Lymph Nodes/PA; Male; Middle Age; Neoplasm Staging; Prognosis; Retrospective Studies; Support, Non-U.S. Gov't. .T Primary hepatic malignancy: the role of liver transplantation. .P JOURNAL ARTICLE. .W Between January 1982 and April 1989, 134 patients with a suspected liver neoplasm were referred to the liver unit, Queen Elizabeth Hospital, Birmingham. In 105 (78 per cent), a primary hepatic neoplasm was histologically confirmed, and 47 patients (45 per cent) proved to have primary hepatocellular carcinoma. Twenty-nine orthotopic liver transplants were performed in 28 of these patients (27 per cent). Twenty patients (71 per cent) survived 30 days or longer (median 11.5 months; range 2-87 months), of whom nine are currently alive. We retrospectively analysed our data to determine the influence of preoperative evaluation, histological type and staging on outcome. Computed tomography proved to be superior to intraoperative assessment (86 versus 58 per cent) in diagnosing tumour positive nodes. Patients with tumour negative lymphadenopathy had a better prognosis. Postoperative stage I/II had a median survival of 16 months (range 3-87 months) compared with 7.5 months (range 2-20 months) for stage III. Non-cirrhotic patients with hepatocellular carcinoma had the best prognosis; cholangiocellular carcinoma and cirrhotic patients with hepatocelluar carcinoma had the worst outcome with no survivors beyond 1 year. Because of the advanced stage of disease at the time of presentation, the value of liver transplantation in primary liver cancer is limited. For those presenting with advanced disease confined to the liver (stage I/II) in whom conventional hepatic resection is not possible, significant benefit can be achieved in selected cases. .A Ismail T; Angrisani L; Gunson BK; Hubscher SG; Buckels JA; Neuberger JM; Elias E; McMaster P. .I 274474 .U 91003276 .S Br J Surg 9101; 77(9):987-8 .M Adult; Bile Ducts, Intrahepatic/*/RA; Case Report; Cholelithiasis/RA/*TH; Female; Gallbladder Diseases/CO; Human; Lithotripsy/*. .T Management of intrahepatic calculi in Caroli's disease by extracorporeal shock wave lithotripsy. .P JOURNAL ARTICLE. .A Lointier PH; Kauffmann P; Francannet P; Pezet D; Chipponi J. .I 274475 .U 91003277 .S Br J Surg 9101; 77(9):989-91 .M Aeromonas; Anastomosis, Roux-en-Y; Animal; Bacterial Infections/PC; Biliary Atresia/*SU; Cholangitis/*PC; Dogs; Intestinal Mucosa/SU; Portoenterostomy, Hepatic/*MT; Postoperative Complications/*PC; Random Allocation; Support, Non-U.S. Gov't. .T Mucosal intussusception to avoid ascending cholangitis. .P JOURNAL ARTICLE. .W Many methods have been devised to prevent ascending cholangitis following Kasai's hepatic portoenterostomy for biliary atresia. To investigate the effectiveness of mucosal intussusception in preventing ascending cholangitis, 20 mongrel dogs were randomized to undergo Roux-en-Y cholecystjejunostomy and common bile duct ligation with or without mucosal intussusception. Aeromonas hydrophila was instilled into the gastrointestinal tract. Bacterial cultures were grown from samples taken from the gallbladders and lower jejunum, and blood chemistry and barium studies were performed. The barium studies showed satisfactory lack of reflux in all ten dogs with mucosal intussusception. Only two of them had positive cultures for Aeromonas from the gallbladder 3 days after bacterial instillation into the jejunum. All ten dogs in the control group had positive cultures for Aeromonas from the gallbladder. Our results showed that the mucosal intussusception group had a significantly lower rate of recovery of organisms from the gallbladder compared with the control group when the organisms were instilled into distal intestine (P less than 0.05). The method is worthy of clinical trial as a means of preventing or treating ascending cholangitis. .A Yeh TJ; Chin TW; Tsai WC; Wei CF. .I 274476 .U 91003278 .S Br J Surg 9101; 77(9):992-5 .M Adult; Aged; Atropine/PD; Dose-Response Relationship, Drug; Female; Human; Male; Manometry; Meperidine/AI/*PD; Middle Age; Morphine/*PD; Muscle Contraction/DE; Naloxone/PD; Oddi's Sphincter/*DE/PH; Support, Non-U.S. Gov't. .T Differing effects of pethidine and morphine on human sphincter of Oddi motility. .P JOURNAL ARTICLE. .W The aim of this study was to evaluate the effects of morphine and pethidine on human sphincter of Oddi motility. The action of these opioids on the sphincter of Oddi was evaluated by means of intraoperative manometry in 36 patients undergoing elective cholecystectomy. Both opioids were given in intravenous cumulative equipotent doses up to a maximum of 10 micrograms/kg morphine or 100 micrograms/kg pethidine. At these doses, morphine increased the mean(s.d.) frequency of contractions from 2.4(1.0) to 7.9(1.6) (P less than 0.001); this effect was reduced by naloxone (0.04 mg bolus, P less than 0.05). Pethidine inhibited the frequency of contractions from 1.5(0.8) to 0.8(0.5) (P less than 0.05); this response was blocked by atropine (0.6 mg bolus, P less than 0.01). Pretreatment with atropine or naloxone reduced the frequency of contractions significantly (P less than 0.05). The results illustrate different responses to pethidine and morphine of the sphincter of Oddi, and provide a pharmacological explanation for the suitability of pethidine over morphine as the analgesic of choice in patients experiencing biliary pain. .A Thune A; Baker RA; Saccone GT; Owen H; Toouli J. .I 274477 .U 91003279 .S Br J Surg 9101; 77(9):996-7 .M Adult; Case Report; Esophageal Diseases/*PA/SU; Female; Granuloma, Plasma Cell/*PA/SU; Human. .T Plasma cell granuloma of the distal oesophagus. .P JOURNAL ARTICLE. .A Seco JL; Claver M; Bengoechea M; Moral G; Santamaria JL. .I 274478 .U 91003280 .S Br J Surg 9101; 77(9):998-9 .M Colorectal Neoplasms/*SU; Female; Human; Intraoperative Care; Liver Neoplasms/DI/*SC/US; Male; Preoperative Care. .T Intraoperative ultrasonography and the detection of liver metastases in patients with colorectal cancer. .P JOURNAL ARTICLE. .W A total of 213 patients with carcinoma of the colon and rectum were examined to detect liver metastases. The study compared preoperative ultrasonography and inspection and palpation of the liver during surgery with intraoperative ultrasonography. Preoperative ultrasonography, inspection and palpation identified 238 metastases in 42 patients. Intraoperative ultrasonography detected 116 previously unrecognized metastatic tumours during 40 surgical procedures (P less than 0.01). High resolution intraoperative ultrasonography is safe and more accurate than preoperative imaging and surgical exploratory methods. The examination is simple to perform and success appears to be related to careful attention to detail. .A Olsen AK. .I 274479 .U 91003674 .S Can J Ophthalmol 9101; 25(5):229-33 .M Acrylic Resins/*; Aged; Aged, 80 and over; Cataract Extraction/*; Chi-Square Distribution; Comparative Study; Female; Human; Hyaluronic Acid/*; Lenses, Intraocular/*; Male; Prospective Studies. .T A prospective comparison of 4% polyacrylamide (Orcolon) and 1% sodium hyaluronate (Healon) in cataract and intraocular lens implant surgery. .P CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL. .W We performed a prospective randomized clinical trial of 4% polyacrylamide (Orcolon) and 1% sodium hyaluronate (Healon) in routine extracapsular cataract extraction with posterior chamber lens implantation or in secondary anterior chamber lens implantation. Seventy consecutive patients were enrolled. The viscoelastic agents were compared in four areas intraoperatively: ease of injection, ease of removal, clarity of field and ability to hold back ocular tissues. Healon was significantly superior to Orcolon in all four areas. Further evaluations were performed on the first day and at 2 weeks postoperatively. Measurements of intraocular pressure (IOP) by Goldmann applanation and evaluations of corneal edema, epithelial keratitis and anterior chamber cellular reaction were recorded. Multivariable statistical analysis revealed only one difference between the two groups: significantly more patients in the Orcolon group (eight cases) than in the Healon group (two cases) had an IOP of 21 mm Hg or greater on the first postoperative day. .A Laflamme MY; Swieca R. .I 274480 .U 91003675 .S Can J Ophthalmol 9101; 25(5):234-8 .M Adult; Aged; Aged, 80 and over; Cataract Extraction/*; Comparative Study; Double-Blind Method; Female; Human; Indomethacin/*PD; Male; Middle Age; Ophthalmic Solutions/PD; Prednisolone/*PD; Pupil/*DE; Support, Non-U.S. Gov't; Time Factors. .T Comparison of prednisolone acetate and indomethacin for maintaining mydriasis during cataract surgery. .P CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL. .W Preoperative topical nonsteroidal anti-inflammatory drugs such as flurbiprofen and indomethacin have been found to maintain mydriasis during cataract surgery. Steroidal anti-inflammatory drugs are commonly used to treat postoperative inflammation, but their effect on the maintenance of intraoperative mydriasis is unknown. Forty-six patients admitted for elective cataract surgery were randomly assigned to one of three treatment groups and received 1% prednisolone acetate, 1% indomethacin or artificial tears four times before surgery, in addition to standardized preoperative dilating drops and intraoperative epinephrine. Pupillary diameter was measured and the time interval noted five times during the surgery. During surgery the indomethacin group lost significantly less mydriasis than the control group. The mydriasis losses of the prednisolone acetate group were between those of the indomethacin and control groups, but these differences did not reach significance. We conclude that prednisolone acetate is less effective than indomethacin for maintaining mydriasis during cataract surgery. .A Dube P; Boisjoly HM; Bazin R; Chamberland G; Laughrea PA; Dube I. .I 274481 .U 91003676 .S Can J Ophthalmol 9101; 25(5):239-42 .M Aged; Analysis of Variance; Cataract Extraction/*; Double-Blind Method; Eye Color; Female; Flurbiprofen/*PD; Human; Intraoperative Care; Male; Preoperative Care; Prostaglandin Antagonists/*PD; Pupil/*DE. .T Effect of flurbiprofen on the maintenance of pupillary dilation during cataract surgery. .P CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL. .W A randomized, double-blind clinical trial was performed to evaluate the effect of flurbiprofen sodium (0.03%), a potent prostaglandin inhibitor, on the maintenance of pupillary dilation during elective extracapsular cataract extraction. Intraoperative pupillary measurements were taken before incision, after lens extraction and following cortex aspiration. The treatment group demonstrated statistically significant maintenance of pupillary area at each stage and in total (p = 0.003). The results indicate that the inhibition of prostaglandin synthesis by flurbiprofen aids significantly in the maintenance of intraoperative pupillary dilation. .A Heinrichs DA; Leith AB. .I 274482 .U 91003677 .S Can J Ophthalmol 9101; 25(5):243-8 .M Adolescence; Adult; Aged; Aged, 80 and over; Canada/EP; Child; Child, Preschool; Comparative Study; Corneal Diseases/EP/PA/*SU; Female; Graft Survival; Human; Keratoplasty, Penetrating/*/SN; Male; Middle Age; Reoperation. .T Changing indications for penetrating keratoplasty in Vancouver, 1978-87. .P JOURNAL ARTICLE. .W Indications for penetrating keratoplasty (PK) were assessed by clinicopathological review of 659 corneal buttons submitted from 1978 to 1987 to the Ophthalmic Pathology Service in Vancouver. Leading indications for PK were bullous keratopathy (22.2%), keratoconus (17.1%), scarring with or without chronic inflammation (13.5%), graft failure (12.1%), scarring or active keratitis secondary to virus (9.0%) and Fuchs' dystrophy (8.3%). The principal factors responsible for graft failure were also judged by clinicopathological correlation. The authors compare their findings with those in other series. .A Damji KF; Rootman J; White VA; Dubord PJ; Richards JS. .I 274483 .U 91003678 .S Can J Ophthalmol 9101; 25(5):249-51 .M Adult; Aged; Case Report; Chloroquine/*AE/ME; Cornea/*ME; Female; Fluorescein Angiography; Fundus Oculi; Human; Hydroxychloroquine/*AE/ME; Male; Overdose/CO/DI; Pupil/DE; Retinal Diseases/*CI/DI. .T Is corneal deposition of antimalarial any indication of retinal toxicity? .P JOURNAL ARTICLE. .W Ninety-five percent of patients on chloroquine demonstrate corneal deposition of the drug with the pupil dilated; less than 10% of patients on hydroxychloroquine show any corneal changes when so examined. I describe one patient on chloroquine and two on hydroxychloroquine who demonstrated large amounts of corneal antimalarial drug, leading to the early diagnosis of definite retinopathy. Examination of the cornea with the pupil dilated may reveal the presence of retinal toxicity in some patients. .A Easterbrook M. .I 274484 .U 91003679 .S Can J Ophthalmol 9101; 25(5):252-5 .M Eyelid Diseases/*TH; Human; Ontario; Ophthalmology; Questionnaires. .T The management of chalazion: a survey of Ontario ophthalmologists. .P JOURNAL ARTICLE. .W Owing to the variability and lack of standardization of chalazion management, a survey of Ontario ophthalmologists was undertaken. The results highlight what ophthalmologists consider to be problems in chalazion management and suggest that a chalazion operation should be treated with the same respect given any other operation. .A Smythe D; Hurwitz JJ; Tayfour F. .I 274485 .U 91003680 .S Can J Ophthalmol 9101; 25(5):256-9 .M Biopsy; Case Report; Chloroquine/TU; Eyelid Diseases/DT/*PA; Female; Human; Middle Age; Sarcoidosis/DT/*PA. .T Sarcoidosis of the eyelid skin. .P JOURNAL ARTICLE. .W A 64-year-old white woman presented with nodular lesions on the arms and face, including both medial canthi and the left upper eyelid. Histopathological examination of the biopsied eyelid lesion and other facial lesions disclosed the presence of noncaseating granulomas strongly suggestive of sarcoidosis. No other evidence of ocular sarcoidosis was present. The patient had clinical, radiologic and laboratory findings consistent with a diagnosis of systemic sarcoidosis. Therapy with chloroquine phosphate led to regression of the cutaneous lesions. .A Brownstein S; Liszauer AD; Carey WD; Nicolle DA. .I 274486 .U 91003681 .S Can J Ophthalmol 9101; 25(5):260-2 .M Acanthamoeba/DE/IP; Acanthamoeba Keratitis/DT/*ET/PA/PS; Adult; Animal; Benzamidines/TU; Biopsy; Case Report; Contact Lenses, Hydrophilic/*AE; Cornea/DE/PS; Human; Male; Neomycin/TU; Polymyxin B/TU. .T Acanthamoeba keratitis with two species of Acanthamoeba. .P JOURNAL ARTICLE. .W We describe a case of Acanthamoeba keratitis related to soft contact lens wear. The patient presented with a 3-week history of severe uniocular pain, radial stromal infiltrates and subepithelial infiltrates with no epithelial defect. Acanthamoeba was cultured from the corneal biopsy specimen, contact lens and lens case. The corneal biopsy culture grew both A. castellani and A. polyphaga as well as Escherichia coli. The patient was treated with topical dibromopropamidine isethionate (Brolene) drops, neomycin and polymyxin B drops and fortified gentamicin drops. Gradual clinical improvement ensued. .A Beattie AM; Slomovic AR; Rootman DS; Hunter WS. .I 274487 .U 91003705 .S Can Med Assoc J 9101; 143(6):459-60 .M Asthma/PC/*TH; Chronic Disease; Emergencies; Human; Physicians, Family; Prognosis. .T Long-term management of asthma [letter; comment] .P COMMENT; LETTER. .A Dean MM. .I 274488 .U 91003706 .S Can Med Assoc J 9101; 143(6):460-1 .M Antihypertensive Agents/*TU; Eating/*; Food Habits/*; Human; Hypertension/DH/*DT. .T Hypertension and eating habits [letter] .P LETTER. .A Watters WW. .I 274489 .U 91003707 .S Can Med Assoc J 9101; 143(6):461, 464-5 .M Adolescence; Child; Head Injuries/MO/RA/*TH; Human; Injury Severity Score/*; Multiple Trauma/CO. .T Management of children with head trauma [letter; comment] .P COMMENT; LETTER. .I 274490 .U 91003708 .S Can Med Assoc J 9101; 143(6):466 .M Great Britain; History of Medicine, 19th Cent.; History of Medicine, 20th Cent.; Human; Incisor/*/IN; Military Dentistry/HI; Military Personnel/*; Oral Health; Tooth Loss/*. .T Traumatic exodontia [letter; comment] .P COMMENT; HISTORICAL ARTICLE; LETTER. .A Sperber GH. .I 274491 .U 91003709 .S Can Med Assoc J 9101; 143(6):466-7 .M Abortion, Induced/*; Abortion, Legal/*; Canada; Female; Human; Patient Advocacy; Pregnancy; Women's Rights. .T Abortion: a right or a treatment? [letter] .P LETTER. .A Ney PG. .I 274492 .U 91003710 .S Can Med Assoc J 9101; 143(6):467-8 .M Drug Industry/*; Drugs/*; Human; Interprofessional Relations/*; Physicians/*. .T A sample argument [letter] [see comments] .P LETTER. .A Rapp MS. .I 274493 .U 91003711 .S Can Med Assoc J 9101; 143(6):468 .M Health Behavior/*; Human; Preventive Medicine/*; Wit and Humor/*. .T Leave me alone [letter] .P LETTER. .A Esdaile DS. .I 274494 .U 91003712 .S Can Med Assoc J 9101; 143(6):473-4 .M Canada; Human; Insurance, Health; Outcome and Process Assessment (Health Care); Practice Management, Medical/*; Quality Assurance, Health Care/*. .T Guidelines are essential for quality assurance in practice [editorial] .P EDITORIAL. .A Scott GW. .I 274495 .U 91003716 .S Can Med Assoc J 9101; 143(6):493-500 .M Acquired Immunodeficiency Syndrome/*ET/PC; Adult; Chicago; Female; Human; HIV Infections/*ET/PC; Male; Middle Age; Occupational Diseases/*ET/PC; Occupational Exposure; Ohio; Ontario; Physicians/*; Professional Practice; Regression Analysis; Risk Factors; Social Environment; Support, Non-U.S. Gov't. .T Physicians' perception of personal risk of HIV infection and AIDS through occupational exposure. .P JOURNAL ARTICLE. .W Physicians' response to acquired immune deficiency syndrome (AIDS) is poorly understood and often attributed to fear of human immunodeficiency virus (HIV) infection through occupational exposure. We surveyed 268 physicians from three geographic regions in North American with different specialties and responsibilities for HIV-positive patients. An important difference was found between the published risk and the physicians' perceived risk of infection after a single occupational exposure. Almost half of the respondents stated that they feared contracting AIDS more than other diseases. The physicians who perceived themselves to be at high physical risk were more likely than the others to report that AIDS had changed the way they interact with their patients (r = 0.26, p less than 0.001). No relation was found between the perception of physical risk and the number of HIV-infected patients (r = -0.07, p = 0.15). However, the perception of social risk showed a small inverse correlation (r = -0.15, p less than 0.02), in which the physicians with more HIV-infected patients reported less concern about negative social consequences. The physicians who perceived themselves to be at high personal risk were more likely than the others to report that surgeons have the right to refuse patients who do not wish to undergo HIV antibody testing (r = -0.16, p less than 0.01 for physical risk; r = -0.29, p less than 0.001 for social risk). Multiple regression analyses indicated that physicians' perception of physical risk was not related to age or sex but was modestly related to income source. The perception of social risk was related to sex and income source. Physicians' perception of personal risk is a crucial, yet often unacknowledged, component of the fight against AIDS. Our findings suggest that lack of attention to this issue is seriously compromising initiatives designed to facilitate physician participation in AIDS care. .A Taylor KM; Eakin JM; Skinner HA; Kelner M; Shapiro M. .I 274496 .U 91003718 .S Can Med Assoc J 9101; 143(6):509-12 .M Apnea/*ET; Calcium/BL; Female; Human; Hypercalcemia/BL/*CO/GE; Infant; Infant, Newborn; Male; Sleep Apnea Syndromes/ET. .T Hypercalcemia in infants presenting with apnea. .P JOURNAL ARTICLE. .W To our knowledge apnea in infants has not been associated with hypercalcemia. We describe seven hypercalcemic infants aged 2 days to 3 months who had presented with apnea; six of the seven were otherwise healthy. The apneic attacks were brief, and normal breathing was restored spontaneously or after tactile stimulation. The attacks stopped and the apnea monitoring was discontinued when the children were 1 month to 2 years of age. The only abnormal finding common to all of the patients was hypercalcemia. Idiopathic infantile hypercalcemia was diagnosed in six of the patients and familial benign hypercalcemia in one. Our findings suggest that determination of the plasma calcium level be included in the investigation of apnea in infancy. .A Kooh SW; Binet A. .I 274497 .U 91003719 .S Can Med Assoc J 9101; 143(6):513-6 .M Adult; Case Report; Female; Human; Intelligence; Middle Age; Phenylalanine/BL; Phenylketonuria/BL/*DI/GE; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Undiagnosed phenylketonuria in adult women: a hidden public health problem. .P JOURNAL ARTICLE; REVIEW; REVIEW OF REPORTED CASES. .A Hanley WB; Clarke JT; Schoonheyt WE. .I 274498 .U 91003720 .S Can Med Assoc J 9101; 143(6):519-21 .M Animal; Cattle; Colitis, Ulcerative/MI; Endotoxins/*/AN; Escherichia coli/CL/*IP; Escherichia coli Infections; Food Microbiology/*; Human; Manitoba; Meat/*; Pilot Projects; Serotyping. .T Verotoxin-producing Escherichia coli in ground beef in Manitoba. .P JOURNAL ARTICLE. .I 274499 .U 91003721 .S Can Med Assoc J 9101; 143(6):523 .M Atherosclerosis/PA/*PP; Human; Remission, Spontaneous. .T Regression of atherosclerosis. .P JOURNAL ARTICLE. .A Moore S. .I 274500 .U 91003722 .S Can Med Assoc J 9101; 143(6):537-9 .M Delivery of Health Care; Emergency Service, Hospital/*/OG; Ethnic Groups/*; Hospitals, Community/OG; Human; Indians, North American/*; Quebec; Transportation of Patients. .T Oka standoff a health care nightmare for native doctor. .P JOURNAL ARTICLE. .A Sutherland R. .I 274501 .U 91003723 .S Can Med Assoc J 9101; 143(6):545-6 .M Cost Control; Health Care Rationing/*/EC/LJ; Human; Insurance, Health; Medicaid; Oregon; United States. .T Oregon tackles the health care rationing issue. .P JOURNAL ARTICLE. .A Silversides A. .I 274502 .U 91003724 .S Can Med Assoc J 9101; 143(6):546, 549 .M Attitude of Health Personnel/*; Canada; Child; Down's Syndrome/PX/*TH; Human; Infant; Pediatrics; Physicians/*; Surgery; Technology, Medical. .T Medical advances, positive attitudes brighten future of Down's children. .P JOURNAL ARTICLE. .A Michaels E. .I 274503 .U 91003725 .S Can Med Assoc J 9101; 143(6):547 .M Child; Down's Syndrome/*CO/TH; Human; Infant; Physicians, Family/*; Professional-Family Relations. .T Family physicians should be aware of Down's-related health problems. .P JOURNAL ARTICLE. .I 274504 .U 91003726 .S Can Med Assoc J 9101; 143(6):555-8 .M Canada; Government/*; Human; Income; Military Medicine; Physicians/*; Private Practice; Public Health Administration/*/EC. .T Public service careers heaven for some MDs, hell for others. .P JOURNAL ARTICLE. .A Cohen L. .I 274505 .U 91003727 .S Can Med Assoc J 9101; 143(7):603-6 .M Animal; Animal Testing Alternatives; Animal Welfare/*; Research. .T The animal rights war [letter] [see comments] .P LETTER. .I 274506 .U 91003728 .S Can Med Assoc J 9101; 143(7):607-9 .M Adult; Female; Human; Hyperlipoproteinemia/BL/*DI/TH; Lipoproteins, HDL Cholesterol/BL; Lipoproteins, LDL Cholesterol/BL; Male; Triglycerides/BL. .T Detecting and treating dyslipoproteinemias [letter] [published erratum appears in Can Med Assoc J 1990 Nov 15;143(10):999] .P LETTER. .I 274507 .U 91003729 .S Can Med Assoc J 9101; 143(7):609-10 .M Adolescence; Adult; Aged; Canada/EP; Human; Risk Factors; Suicide/*PC/SN. .T Preventing suicide [letter] .P LETTER. .I 274508 .U 91003730 .S Can Med Assoc J 9101; 143(7):611 .M Acquired Immunodeficiency Syndrome/DT; Azathioprine/*/TU; Human; Male; Nomenclature/*; Prescriptions, Drug; Zidovudine/*/TU. .T Azathioprine or azidothymidine? [letter] [see comments] .P LETTER. .A Landis SJ. .I 274509 .U 91003732 .S Can Med Assoc J 9101; 143(7):613 .M Computer Systems/*; Databases, Bibliographic; Software/*. .T ISI Sci-Mate Software System not available [letter; comment] .P COMMENT; LETTER. .A Roberts J. .I 274510 .U 91003733 .S Can Med Assoc J 9101; 143(7):613-4 .M Abortion, Induced/*; Canada; Ethics, Medical/*; Female; Hippocratic Oath/*; Human; Pregnancy; Societies, Medical. .T CMA's code of ethics [letter] .P LETTER. .A Brown RH. .I 274511 .U 91003734 .S Can Med Assoc J 9101; 143(7):619-22 .M Abstracting and Indexing/*; Publishing/*; Research; Review Literature/*; Writing. .T Structured abstracts of original research and review articles. .P JOURNAL ARTICLE. .A Squires BP. .I 274512 .U 91003735 .S Can Med Assoc J 9101; 143(7):625-7 .M Acquired Immunodeficiency Syndrome/*EP; Canada/EP; Ethics, Medical/*; Human; HIV Seroprevalence/*; Jurisprudence/*; Population Surveillance. .T Guidelines on ethical and legal considerations in anonymous unlinked HIV seroprevalence research. Federal Centre for AIDS Working Group on anonymous unlinked HIV seroprevalence [see comments] .P GUIDELINE; JOURNAL ARTICLE. .I 274513 .U 91003736 .S Can Med Assoc J 9101; 143(7):629-32 .M Canada; Communication; Feedback; Government; Health Policy; Human; Interprofessional Relations; Policy Making; Practice Management, Medical/*/ST; Professional Review Organizations/OG; Quality Assurance, Health Care/*. .T Guidelines for medical practice: 2. A possible strategy. .P JOURNAL ARTICLE. .W The recognition that much current medical practice is based on incomplete scientific evidence has led to calls for the generation of guidelines for optimal patterns of practice. These guidelines must be developed from a synthesis of existing scientific data ideally obtained from randomized clinical trials. However, at present we may have to rely on less satisfactory data and the views of experts in the field. The primary purpose of these initiatives must be to improve patient care. The Ontario Medical Association has made recommendations on how such guidelines should be produced, and in a recent survey a substantial majority of family physicians supported them. There is general agreement that the coordinating body should be independent of government and other interested parties. In addition, the medical profession must have the primary role, and a number of medical organizations should also be represented. We propose a possible structure for a group charged with developing guidelines for medical practice at a provincial level and on an experimental basis. Recommendations are made on its membership, function and relationship with other organizations. The identification and diffusion of justifiable, scientific practice patterns will help reduce waste of scarce resources, maintain the role of the profession as guardian of the quality of care and ultimately benefit the patient. .A Peachey DK; Linton AL. .I 274514 .U 91003737 .S Can Med Assoc J 9101; 143(7):633-9 .M Aged; Depression/*TH; Human; Meta-Analysis; Prognosis. .T The prognosis of depression in the elderly. .P JOURNAL ARTICLE; REVIEW; REVIEW, MULTICASE. .W Controversy prompted a systematic and critical review of original research articles to determine the prognosis of depression in the elderly. A search of three computer databases for articles published from January 1980 to May 1989 and of the bibliographies of articles located revealed 10 reports, involving 990 subjects, that met the following inclusion criteria: original research, published in English or French since 1950, sample of at least 25 patients, inclusion of only patients over 60 years, mean follow-up period of 1 year or more and description of the patients' mental state during follow-up. The methods and study designs were then assessed with the use of the criteria for prognostic studies established by McMaster University Health Sciences Centre, Hamilton, Ont. All of the studies had serious, multiple flaws. Nevertheless, when the results were combined it appeared that at least 60% of the patients remained well or had relapses with recovery (mean follow-up 31.9 months); up to 25% remained continuously ill. Physical illness, cognitive impairment and severe depressive symptoms were frequently related to poor prognosis; most of the social factors studied were not related to prognosis. Future studies must pay attention to methods and design, particularly the composition of study populations, the assessment of outcomes and the control of extraneous prognostic factors. .A Cole MG. .I 274515 .U 91003738 .S Can Med Assoc J 9101; 143(7):641-6 .M Bacterial Infections/*CO/PA; Deglutition Disorders/CO; Diarrhea/CO; Duodenal Diseases/CO/PA; Esophagitis/CO/PA; Female; Gastritis/CO/PA; Gastrointestinal Diseases/*CO/PA/PP; Human; HIV Infections/*CO/PA/PP; HIV Seropositivity/*; Intestinal Absorption/*PH; Male; Opportunistic Infections/CO; Proctitis/CO/PA; Xylose/PK. .T Gastrointestinal function and structure in HIV-positive patients. .P JOURNAL ARTICLE. .W We examined 19 patients (17 men) with human immunodeficiency virus (HIV) infection and gastrointestinal symptoms to determine whether those symptoms were due to either a gastrointestinal tract infection or a defect in mucosal absorption because of an enteropathy. The erythrocyte folate and serum vitamin B12 levels were within normal limits in all of the patients. The serum ferritin level was elevated in 12. The xylose absorption test results were abnormal in 8 of the 13 patients able to complete the study. None of the duodenal aspirates yielded a pathogen. Light microscopy revealed nonspecific lymphocytic inflammation without infection in the stomach (in seven patients), the esophagus (in five), the duodenum (in two) and the rectum (in two). However, biopsy specimens were positive for Candida albicans in the esophagus (four patients), cytomegalovirus in the esophagus (one) and the rectum (two), Helicobacter pylori in the antrum (two), Treponema infection in the rectum (two) and Mycobacterium avium-intracellulare in the small intestine (one). Only three patients had a normal series of biopsy specimens. All of the patients had similar ultrastructural changes at the epithelial-stromal junction of the antral glands and in the intestinal crypts. We conclude that abnormal biochemical and endoscopic findings are common in HIV-positive patients with gastrointestinal symptoms. Defects in carbohydrate absorption and ultrastructural changes may be responsible for some aspects of HIV enteropathy. .A Sutherland LR; Church DL; Gill MJ; Kelly JK; Hwang WS; Bryant HE. .I 274516 .U 91003739 .S Can Med Assoc J 9101; 143(7):647-8 .M Air Pollutants/*AN; Carbon Monoxide/*AN; Carbon Monoxide Poisoning/ET; Environmental Exposure/*; Environmental Monitoring/IS; Human; Manitoba; Transportation/*; Ventilation. .T Carbon monoxide levels in indoor tractor-pull events--Manitoba. .P JOURNAL ARTICLE. .I 274517 .U 91003741 .S Can Med Assoc J 9101; 143(7):655-6 .M Acquired Immunodeficiency Syndrome/*; Attitude to Health/*; Books/*; Child; Child, Preschool; Health Education/*; Human; HIV Infections/*; Interpersonal Relations. .T Tolerance for HIV patients goal of MD's book for children. .P JOURNAL ARTICLE. .A Johnston C. .I 274518 .U 91003742 .S Can Med Assoc J 9101; 143(7):660, 662 .M Acquired Immunodeficiency Syndrome/*/PX; Attitude of Health Personnel/*; Communication; Female; Human; HIV Infections/*/PX; Male; Physician-Patient Relations/*. .T Use discretion in treating HIV patients, FPs told. .P JOURNAL ARTICLE. .A Trent B. .I 274519 .U 91003743 .S Can Med Assoc J 9101; 143(7):665-6 .M Canada; Costs and Cost Analysis; Human; Malpractice/*EC/LJ. .T Damage awards to patients up 48% in 1989, CMPA reports. .P JOURNAL ARTICLE. .A Goldman B. .I 274520 .U 91003744 .S Can Med Assoc J 9101; 143(7):668 .M Computer Systems/*; Emergencies; Equipment and Supplies, Hospital/*; Heart Arrest/*TH; Human. .T The Crashcart Companion. .P JOURNAL ARTICLE. .A Goldman B. .I 274521 .U 91003745 .S Can Med Assoc J 9101; 143(7):669-70 .M Human; Medicine/*; Technology, Medical; Wit and Humor/*. .T Searching for the lemming gene. .P JOURNAL ARTICLE. .A Taylor PJ. .I 274522 .U 91003746 .S Can Med Assoc J 9101; 143(8):705-7 .M Interprofessional Relations/*; Job Satisfaction/*; Nurses/*; Physicians/*. .T Here's why nurses are quitting [letter; comment] .P COMMENT; LETTER. .I 274523 .U 91003747 .S Can Med Assoc J 9101; 143(8):707-9 .M Attitude to Health/*EH; Canada; Female; Home Childbirth/*; Human; Pregnancy; Questionnaires. .T Interest in alternative birthplaces among women in Ottawa-Carleton [letter; comment] .P COMMENT; LETTER. .I 274524 .U 91003748 .S Can Med Assoc J 9101; 143(8):709 .M Embolism/*ET; Female; Human; Laser Surgery/*AE; Uterus/*SU. .T Embolism during intrauterine laser surgery [letter] [see comments] .P LETTER. .A Weber F; Wallace B. .I 274525 .U 91003749 .S Can Med Assoc J 9101; 143(8):709-10 .M Ascorbic Acid/*UR; Human; Longevity/*. .T My quest for eternal youth [letter] .P LETTER. .A Vogel MJ. .I 274526 .U 91003750 .S Can Med Assoc J 9101; 143(8):711 .M Hip Dislocation, Congenital/*EC; Human; Infant, Newborn; Mass Screening/*EC. .T Screening for congenital dislocation of the hip: an economic appraisal [letter] .P LETTER. .A Marzouk MS. .I 274527 .U 91003751 .S Can Med Assoc J 9101; 143(8):713-6 .M Acquired Immunodeficiency Syndrome/*TM; Adolescence; Canada; Child; Female; Health Surveys; Human; Male; Sex Behavior/*; Sexually Transmitted Diseases/*TM. .T Implications of the Canada youth and AIDS study for health care providers [editorial] .P EDITORIAL. .A Bowie WR; Warren WK; Fisher WA; MacDonald NE; Doherty JA; Wells GA. .I 274528 .U 91003752 .S Can Med Assoc J 9101; 143(8):717-8 .M Adolescence; Canada; Health Promotion/*MT; Human; Physician's Role; Sexually Transmitted Diseases/*PC. .T Prevention of sexually transmitted diseases: whose responsibility? What message? [editorial] .P EDITORIAL. .A Hankins CA. .I 274529 .U 91003753 .S Can Med Assoc J 9101; 143(8):721-3 .M Canada; Chemistry, Clinical/IS; Cholesterol/*BL; Human; Quality Control/*. .T Out-of-laboratory measurement of the blood cholesterol level. Canadian Society of Clinical Chemists Task Force on Out-of-Laboratory Blood Cholesterol Measurement. .P JOURNAL ARTICLE. .I 274530 .U 91003755 .S Can Med Assoc J 9101; 143(8):733-7 .M Aging/*ME; Female; Ferritin/BL; Follow-Up Studies; Gestational Age; Human; Infant Food/*; Infant, Low Birth Weight/*; Infant, Newborn; Iron/AD/*ME; Male; Nutritional Status; Support, Non-U.S. Gov't. .T Iron status of very-low-birth-weight infants during the first 15 months of infancy. .P JOURNAL ARTICLE. .W The adequacy of iron stores in infants of very low birth weight (defined as less than 1500 g) in Canada is unknown. We monitored the iron status of 81 such infants at 3, 6, 9, 12 and 15 months of age. All of the infants were fed formula fortified with iron (13 mg/L) for at least 6 months, starting at 2 months of age. The plasma ferritin level decreased after the formula was no longer used. Although 90% of the infants were given cereal fortified with iron (30 mg of iron per 100 g) by 9 months of age, the plasma ferritin level continued to decrease. The level was less than 10 micrograms/L in 54% of the infants at 12 months of age and in 74% at 15 months; this indicated depleted iron stores. Because of delayed development very-low-birth-weight infants eat small amounts of cereal and therefore require iron-fortified formula throughout infancy. .A Friel JK; Andrews WL; Matthew JD; Long DR; Cornel AM; Cox M; Skinner CT. .I 274531 .U 91003756 .S Can Med Assoc J 9101; 143(8):740-5 .M Adult; Ambulatory Care Facilities/*UT; Attitude to Health/*; Consumer Satisfaction/*; Family Practice; Female; Human; Male; Ontario; Questionnaires; Support, Non-U.S. Gov't. .T Walk-in clinics: implications for family practice [see comments] .P JOURNAL ARTICLE. .W To understand better the reasons for the growth in popularity of walk-in clinics in Canada we surveyed 321 patients with a regular physician in Toronto who attended a walk-in clinic in the same city over a 16-day period in February 1988. They were asked their reason for attending the clinic, their perception of the urgency of their problem, their choices as alternatives to walk-in clinics and their satisfaction and concerns with the type of care received at the clinic. The three most common reasons for attending the clinic were convenient location (in 33% of the cases), inability to see their regular physician soon enough (in 16%) and no appointment needed (in 13%). Most (80%) of the patients felt that they needed medical attention within 24 hours after the onset of their problem. Most (83%) of the respondents would have sought medical attention at another walk-in clinic, from their regular physician or at an emergency department had the clinic been closed. Only 36% and 18% of the patients respectively responded that their regular physician worked evenings or weekends. Most of the visits to the clinic were outside regular weekday business hours. The level of satisfaction with the service received at the clinic was high. The extended hours and no-appointment philosophy of walk-in clinics, coupled with family physicians' reluctance to work evenings and weekends, have made such clinics an attractive option for patients with primary care problems that they believe require prompt attention. .A Rizos J; Anglin P; Grava-Gubins I; Lazar C. .I 274532 .U 91003757 .S Can Med Assoc J 9101; 143(8):747-9 .M Aged; Case Report; Chloroquine/TU; Female; Ferrous Compounds/*AE; Human; Porphyria/*CI/DT; Porphyrins/UR. .T Porphyria cutanea tarda due to ferrous gluconate. .P JOURNAL ARTICLE. .A Ginsburg AD; Margesson LJ; Feleki K. .I 274533 .U 91003758 .S Can Med Assoc J 9101; 143(8):751-3 .M Canada/EH; Disease Outbreaks/*PC; Erythromycin/TU; Human; Infant; Pertussis Vaccine/AD; Vaccination/*; Whooping Cough/DT/*EP/PC. .T Management of people exposed to pertussis and control of pertussis outbreaks [see comments] .P JOURNAL ARTICLE. .I 274534 .U 91003759 .S Can Med Assoc J 9101; 143(8):755 .M Animal; Atherosclerosis/*ET; Cornea/BS; Human; Models, Cardiovascular; Neovascularization/*PP; Rabbits; Rats. .T Neovascularization and the atherosclerotic plaque. .P JOURNAL ARTICLE. .A Brem S. .I 274535 .U 91003760 .S Can Med Assoc J 9101; 143(8):762-5, 768-9 .M Blood Banks/EC/*OG; Canada; Human; Red Cross. .T Canada's blood collection system should be reorganized, critics say [see comments] .P JOURNAL ARTICLE. .A Morgan PP; Cohen L. .I 274536 .U 91003761 .S Can Med Assoc J 9101; 143(8):770-3 .M Canada; Human; Military Medicine/*OG; Physician's Role; War. .T Military MDs used to peace prepare for war [see comments] .P JOURNAL ARTICLE. .A Jones D. .I 274537 .U 91003762 .S Can Med Assoc J 9101; 143(8):781, 783 .M Canada; Education, Medical/*TD; Physicians, Women/*. .T Women close in on 50% share of places in Canada's medical schools. .P JOURNAL ARTICLE. .A Sullivan P. .I 274538 .U 91003763 .S Can Med Assoc J 9101; 143(8):788-9 .M Critical Care; Human; Intensive Care Units/*; Internship and Residency/*; Male. .T End of shift. .P JOURNAL ARTICLE. .A Patterson R. .I 274539 .U 91003764 .S Can Med Assoc J 9101; 143(8):790-1 .M Cerebral Ischemia, Transient/*DI; Human; Male; Medical History Taking; Middle Age. .T With TIAs, MDs cannot rely on patients to provide a meaningful history. .P JOURNAL ARTICLE. .A Kalsner J; Kalsner S. .I 274540 .U 91003839 .S Cancer 9101; 66(7):1449-52 .M Aged; Female; Human; Liver Neoplasms/SC; Lymphatic Metastasis; Male; Middle Age; Neoplasm Staging; Proglumide/*TU; Receptors, Cholecystokinin/*DE; Stomach Neoplasms/DT/*MO/PA; Survival Rate. .T The effect of the gastrin receptor antagonist proglumide on survival in gastric carcinoma. .P CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL. .W Gastric cancer remains a disease with a very poor prognosis, and there is no safe and effective form of therapy for advanced disease. Evidence is now abundant to show that gastrin stimulates the growth of both gastric and colorectal cancer cells in vitro and in vivo, and that blockade of gastrin receptors can prolong survival in xenografted nude mice. We have thus performed a randomized, controlled study of the gastrin/cholecystokinin receptor antagonist proglumide as therapy in 110 patients with gastric carcinoma. Proglumide had no overall effect on survival (Mantel-Cox statistic = 0.5, P = 0.48). The 95% confidence interval for the proglumide treated group was 260 to 474 days compared to 230 to 372 days for the control group. No significant difference was seen with proglumide, which has a relatively low affinity with the gastrin receptor and also has partial agonist activity. Drugs that are far more specific and potent gastrin receptor antagonists are becoming available, which may have a greater effect on survival, and further clinical trials of such compounds are clearly indicated to determine the efficacy of hormonal control of gastrointestinal malignancy. .A Harrison JD; Jones JA; Morris DL. .I 274541 .U 91003840 .S Cancer 9101; 66(7):1453-60 .M Adult; Aged; Antineoplastic Agents, Combined/AE/*TU; Bleomycins/AD; Carcinoma, Squamous Cell/*DT; Cisplatin/AD; Combined Modality Therapy; Drug Administration Schedule; Female; Fluorouracil/AD; Follow-Up Studies; Head and Neck Neoplasms/*DT; Human; Hydroxyurea/AD; Male; Middle Age; Mitomycins/AD; Nasopharyngeal Neoplasms/*DT; Neoplasm Staging; Remission Induction; Survival Rate. .T Induction chemotherapy with a new regimen alternating cisplatin, fluorouracil with mitomycin, hydroxyurea and bleomycin in carcinomas of nasopharynx or other sites of the head and neck region. .P JOURNAL ARTICLE. .W Sixty-six patients with locally advanced (Stages III and IV) carcinoma of the head and neck were treated with three cycles of induction chemotherapy, consisting of cisplatin, fluorouracil (FU) infusion, bleomycin, mitomycin, and hydroxyurea, followed by radiotherapy and/or surgery. There were 48 men and 18 women with a median age of 55 years (range, 18 to 75 years) and Karnofsky performance status of 80 (range, 40 to 90). Primary site was nasopharynx (28 patients), followed by larynx (12) and others (26). Forty-one (62%) patients were presented with Stage IV disease. The response rate to induction chemotherapy was 27% complete response, 50% partial response, 20% stable disease, and 3% progressive disease. There was no significant difference in response rate between patients with cancer of nasopharynx or other sites (P greater than 0.1). Survival was 61% at 24 months. Patients with cancer of nasopharynx had a better survival than those with other primaries (P = 0.033). Toxicities from chemotherapy included alopecia (73%), nausea/vomiting (66%), leukopenia (54%), stomatitis (36%), anemia (32%), thrombocytopenia (16%), and diarrhea (9%). Grade IV toxicity was not observed. Induction chemotherapy with this new regimen resulted in a high response rate but may not be superior to cisplatin and FU alone. It can be safely combined with radiotherapy as a potentially curative therapy in squamous cell carcinoma of the head and neck. Chemotherapy followed by radiation therapy may yield survival similar to radical surgery in laryngeal and other head and neck cancers. .A Fountzilas G; Daniilidis J; Sridhar KS; Kalogera-Fountzila A; Zaramboukas T; Sombolos K; Destouni-Salem E; Vritsios A; Tourkantonis A. .I 274542 .U 91003841 .S Cancer 9101; 66(7):1461-7 .M Adult; Aged; Antineoplastic Agents, Combined/TU; Breast Neoplasms/DI/MO/*TH; Combined Modality Therapy; Female; Follow-Up Studies; Human; Incidence; Lymphatic Metastasis/*DI; Mastectomy; Middle Age; Neoplasms, Unknown Primary/DI/*TH; Radiation Injuries/EP; Radiotherapy Dosage; Support, U.S. Gov't, P.H.S.; Survival Rate. .T Treatment of patients with isolated axillary nodal metastases from an occult primary carcinoma consistent with breast origin. .P JOURNAL ARTICLE. .W The records of 42 patients who had axillary metastases compatible with a clinically occult breast primary were reviewed. Forty patients had mammography performed as part of their evaluations. Mastectomy yielded the primary tumor in one of 13 patients; biopsy yielded positive results in one of five. Among the 29 patients who did not undergo mastectomy, 16 received breast irradiation, and 13 were simply observed for signs of the primary tumor. For the patients who did not undergo mastectomy, the 5-year actuarial risk for appearance of a primary was 17% in the irradiated group versus 57% in the nonirradiated group (P = 0.06). Patterns of failure are correlated with stage and local and systemic therapy. The results affirm our belief that patients with axillary metastases histologically consistent with breast tumor should be treated identically to patients with similar nodal stages and proven breast primaries. .A Ellerbroek N; Holmes F; Singletary E; Evans H; Oswald M; McNeese M. .I 274543 .U 91003842 .S Cancer 9101; 66(7):1468-71 .M Adolescence; Antineoplastic Agents, Combined/AE/*TU; Child; Child, Preschool; Combined Modality Therapy; Female; Heart Neoplasms/TH; Heart Transplantation/*; Human; Infant; Liver Neoplasms/TH; Liver Transplantation/*; Lung Neoplasms/SC/TH; Male; Neoplasms/*DT/MO/SU; Peritoneal Neoplasms/SC/TH; Survival Rate. .T Cancer chemotherapy after solid organ transplantation. .P JOURNAL ARTICLE. .W To assess how well chemotherapy is tolerated after solid organ transplantation, we reviewed our experience at the Children's Hospital of Pittsburgh with five patients aged 1 to 12 years. Four patients had a liver transplant, indications for which were hepatoblastoma in two patients, hepatic failure secondary to Wilms' tumor chemoradiotherapy in one patient, and familial intrahepatic cholestasis in one patient. A fifth patient received a cardiac transplant for unresectable angiosarcoma of the right atrium. After transplant, chemotherapy was given for the treatment of the primary malignancy in four of the patients. The patient with familial intrahepatic cholestasis received chemotherapy for secondary lymphoproliferative disease that had not responded to the cessation of immunosuppression. All patients other than this patient were on immunosuppression with prednisone (0.5 to 2 mg/kg daily) and cyclosporine (to maintain serum levels at 800 to 1000 ng/ml radioimmunoassay) throughout the duration of chemotherapy. Courses of chemotherapy included one or more of the following agents: Adriamycin (Adr, 20 mg/m2 daily, three patients), Cyclophosphamide (Ctx, 1 gm/m2, one patient), cisplatin (CDDP, 90 mg/m2, one patient), Vincristine (Vcr, greater than 0.75 to 1.5 mg/m2, three patients), Actinomycin D (Act-D, 7.5 micrograms/kg, one patient), Ifosfamide (I, 1800 mg/m2, one patient) and Etoposide (VP-16, 100 mg/m2, one patient). All patients received greater than or equal to 3 courses (range, 3 to 9; mean, 5) of chemotherapy every 3 to 4 weeks. Dose reductions were made because of neutropenia in three patients but none were greater than 50%. Severe rejection was seen in one patient who had, however, manifested evidence of rejection prior to his first postoperative course of chemotherapy. No nephro or cardiac toxicity was seen. This preliminary experience suggests that chemotherapy is well tolerated after solid organ transplantation. .A Horn M; Phebus C; Blatt J. .I 274544 .U 91003843 .S Cancer 9101; 66(7):1472-4 .M Aged; Antineoplastic Agents, Combined/*TU; Autopsy; Carmustine/AD; Case Report; Cyclophosphamide/AD; Female; Human; Melphalan/AD; Multiple Myeloma/*DT/PA; Prednisone/AD; Remission Induction; Vincristine/AD. .T Autopsy-documented cure of multiple myeloma 14 years after M2 chemotherapy. .P JOURNAL ARTICLE. .W Multiple myeloma was diagnosed in a 65-year-old woman in 1974 who thereafter received five-drug M2 chemotherapy. All protein abnormalities subsequently returned to normal and serial bone marrow studies documented complete bone marrow remission. Destructive bone lesions persisted radiographically, but did not progress. In 1987, a localized sigmoid adenocarcinoma was resected. In 1988, the patient presented with multiple brain metastases associated with a primary pulmonary adenocarcinoma that proved rapidly fatal. At autopsy, no evidence of multiple myeloma was found. This report describes the first tissue-documented cure of multiple myeloma 14 years after diagnosis and initiation of M2 chemotherapy. The possible association of multiple myeloma with other malignancies is also discussed. .A van Hoeven KH; Reed LJ; Factor SM. .I 274545 .U 91003844 .S Cancer 9101; 66(7):1475-9 .M Adult; Ameloblastoma/*DT/SC; Antineoplastic Agents, Combined/*TU; Case Report; Cisplatin/AD; Cyclophosphamide/AD; Doxorubicin/AD; Female; Human; Lung Neoplasms/*DT/SC; Mandibular Neoplasms/PA. .T Pulmonary metastases from ameloblastoma of the mandible treated with cisplatin, adriamycin, and cyclophosphamide. .P JOURNAL ARTICLE. .W A case of delayed pulmonary metastases from an ameloblastoma of the mandible, which occurred 20 years after surgical resection of the primary tumor but with no recurrence at the primary site, is reported. Combination chemotherapy using cisplatin, adriamycin, and cyclophosphamide has produced a very good clinical and radiologically documented response in this case. .A Ramadas K; Jose CC; Subhashini J; Chandi SM; Viswanathan FR. .I 274546 .U 91003845 .S Cancer 9101; 66(7):1480-7 .M Adult; Aged; Aged, 80 and over; Biopsy, Needle/EC/*MT; Breast Neoplasms/*DI; Carcinoma in Situ/PA; Carcinoma, Ductal/PA; Evaluation Studies; Female; Human; Mammography/*MT; Middle Age; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; Support, Non-U.S. Gov't. .T Prospective evaluation of radiologically directed fine-needle aspiration biopsy of nonpalpable breast lesions. .P JOURNAL ARTICLE. .W The application of fine-needle aspiration biopsy (FNAB) to the diagnosis of nonpalpable breast lesions was evaluated with a new method which uses standard needle localization under mammographic guidance to assure accurate sampling by FNAB. This method was prospectively applied to 100 mammographically detected breast lesions in 100 women (mean age, 53 years). All 100 patients underwent surgical excision of these nonpalpable lesions after cytologic aspiration. Sufficient aspirated material was obtained for cytologic diagnosis from 91 patients (91%). The histologic and cytologic interpretations were then compared. Twenty malignancies were ultimately diagnosed by histology (12 invasive ductal carcinoma, six ductal carcinoma in situ, and two lobular carcinoma in situ), of which 17 had been cytologically diagnosed. There were no false-positive diagnoses of malignancy by FNAB. False-negative readings (3.3%) included two cases of lobular carcinoma in situ and one case of ductal carcinoma in situ. This technique thus demonstrated a sensitivity of 85%, specificity of 100%, and overall diagnostic accuracy of 96.7% for the nonsurgical detection of malignancy in nonpalpable breast lesions. These results suggest that the established safety, reliability, and cost-effectiveness of FNAB can be maintained in this clinical setting. This procedure may obviate the need for open surgical biopsy in those patients with an unequivocal diagnosis of malignancy. It can also be done using standard techniques and equipment available in many community hospitals. .A Masood S; Frykberg ER; McLellan GL; Scalapino MC; Mitchum DG; Bullard JB. .I 274547 .U 91003846 .S Cancer 9101; 66(7):1488-92 .M Adult; Case Report; Cervix Neoplasms/PA/*RT; Female; Follow-Up Studies; Human; Lumbosacral Plexus/*RE; Neoplasm Staging; Peripheral Nerve Diseases/ET; Radiation Injuries/*ET; Radiotherapy Dosage. .T Sacral plexus injury after radiotherapy for carcinoma of cervix. .P JOURNAL ARTICLE. .W A 42-year-old woman developed lower extremity weakness and sensory loss 1 year after external and intracavitary radiotherapy for Stage IB carcinoma of cervix. She has been followed for 5 years posttreatment, and the neurologic abnormalities have persisted, but no evidence of recurrent carcinoma has been found. We believe this to be a rare case of sacral plexus radiculopathy developing as a late complication after radiotherapy. Suggestions are made for improving the radiotherapy technique to prevent this complication in future cases. .A Stryker JA; Sommerville K; Perez R; Velkley DE. .I 274548 .U 91003847 .S Cancer 9101; 66(7):1493-8 .M Antibodies, Monoclonal; Antigens, Neoplasm/*AN; Antigens, Surface/*AN; Carcinoma, Squamous Cell/*IM/SC; Human; Immunoenzyme Techniques; Laryngeal Neoplasms/*IM; Support, Non-U.S. Gov't. .T Relationship of 4F2 antigen with local growth and metastatic potential of squamous cell carcinoma of the larynx. .P JOURNAL ARTICLE. .W The 4F2 antigen is a cell-membrane glycoprotein which arises early in the G0-G1 phases of the cell cycle. This molecule is present in all established human cell lines and most malignant human cells. The authors used an indirect immunophosphatase method to study 50 squamous cell carcinomas of the larynx and ten lymph-node metastases, corresponding to six primary tumors, for 4F2 expression. The tumors showed several patterns of 4F2 staining which were correlated with different behaviors and prognoses of the neoplasms. Three different patterns (no staining, peripheral staining, and diffuse 4F2 expression) are described as are their relationships with metastatic behavior of the carcinomas. Tumors with metastases were found only in the third group (P = 0.0001). These results led to the following conclusions: (1) the 4F2 antigen is present in squamous cell carcinomas; (2) its distribution reflects the tumor-spreading pattern; and (3) it correlates with differentiation and metastatic behavior. .A Esteban F; Ruiz-Cabello F; Concha A; Perez Ayala M; Delgado M; Garrido F. .I 274549 .U 91003848 .S Cancer 9101; 66(7):1499-504 .M Aged; Carcinoma, Bronchogenic/*IM; Cells, Cultured; Female; Human; Interferons/PD; Interleukin-2/PD; Killer Cells, Lymphokine-Activated/DE/*IM; Killer Cells, Natural/DE/*IM; Lung Neoplasms/*IM; Male; Middle Age; Support, Non-U.S. Gov't. .T In vitro natural killer and lymphokine-activated killer activity in patients with bronchogenic carcinoma. .P JOURNAL ARTICLE. .W The authors examined peripheral blood mononuclear cells from 45 patients with bronchogenic carcinoma to determine natural killer (NK) and lymphokine-activated killer (LAK) activity after in vitro incubation with media alone or media plus interferon gamma (IFN, 200 U/ml) and/or interleukin-2 (IL-2, 100 U/ml). Our results show that lymphocytes from patients with bronchogenic carcinoma can acquire LAK activity, but the level of activity acquired was significantly lower compared with lymphocytes from 25 control subjects when IL-2 cultures were supplemented with 10% autologous human serum (AHS) (15.6% +/- 2.1% specific release versus 26.0% +/- 2.9% specific release, P = 0.004). The LAK activity, defined as cytotoxicity of an NK-resistant cell line, of the patients' lymphocytes was augmented when cells were cultured with both IL-2 and IFN compared with IL-2 alone (P = 0.0001, paired t-test). Control subjects were unchanged (P = 0.09). There was no significant difference between groups of patients with different histologic types of tumor or different stages of disease. The NK activity, defined as killing of NK-sensitive K-562 target cells, of the patients' lymphocytes was not significantly different from that of the controls' lymphocytes (42.8% +/- 3.0% specific release versus 49.3% +/- 3.3% specific release, P = 0.16). These studies indicate the feasibility of IL-2 and IFN therapy in patients with bronchogenic carcinoma. .A Dunlap NE; Lane VG; Cloud GA; Tilden AB. .I 274550 .U 91003849 .S Cancer 9101; 66(7):1505-12 .M Aged; Aged, 80 and over; Antigens, Neoplasm/*AN/BL; Carcinoma, Squamous Cell/*IM; Esophageal Neoplasms/*IM; Female; Human; Immunoenzyme Techniques; Lung Neoplasms/*IM; Male; Middle Age. .T Tumor-antigen 4. Its immunohistochemical distribution and tissue and serum concentrations in squamous cell carcinoma of the lung and esophagus. .P JOURNAL ARTICLE. .W The immunohistochemical distribution and concentrations of tumor-antigen 4 (TA-4) in tissues and serum were determined in patients with benign and malignant diseases, including 27 patients with squamous cell carcinoma (SCC; 15 in the lung and 12 in the esophagus). Tumor-antigen 4 immunoreactivity was present in the cytoplasm of many SCC tissues, especially in the hyperparakeratotic region, and in the cytoplasm of differentiated squamous cells of the intermediate layer of normal epithelia of various organs, but not in those of other types of lung cancers or benign pulmonary diseases. Consistent with the results of immunostaining, the TA-4 concentrations in SCC tissues of the lung, esophagus, and normal squamous epithelia were much higher than in those of lung cancer other than SCC, benign pulmonary diseases, normal lung, and submandibular gland tissues. The TA-4 concentration in SCC tissue tended to increase with increasing grades of differentiation. Serum TA-4 was elevated in 15 of 27 patients with SCC but in no patients with other types of lung cancer or benign diseases. These results indicate that TA-4 is an antigen related to the differentiation of squamous cells and that tumor cells of SCC can release a large amount of TA-4 into circulation whereas normal squamous epithelia cannot. .A Mino-Miyagawa N; Kimura Y; Hamamoto K. .I 274551 .U 91003850 .S Cancer 9101; 66(7):1513-6 .M Adult; Aged; Carcinoma, Renal Cell/DT; Female; Human; Interleukin-2/*AE/TU; Kidney Neoplasms/DT; Male; Melanoma/DT; Middle Age; Myocardial Infarction/*CI/PA; Myocarditis/*CI/PA; Myocardium/PA; Necrosis/CI; Organ Weight. .T Myocarditis or acute myocardial infarction associated with interleukin-2 therapy for cancer. .P JOURNAL ARTICLE. .W The hearts of eight patients aged 22 to 67 years (mean, 41 years) who died during or within 4 days of interleukin-2 (IL-2) based immunotherapy for treatment of renal cell carcinoma or melanoma were studied at necropsy. Death resulted from combined cardiorespiratory failure in two patients, sepsis in four patients, acute myocardial infarction in one patient, and myocarditis in one patient. Transmural left ventricular necrosis was present in one of the two patients with significant atherosclerotic coronary artery narrowing. Noninfectious myocarditis was present in five patients: the inflammatory infiltrate was lymphocytic in four and composed of a mixture of eosinophils and lymphocytes in one. Although treatment-related deaths associated with high-dose IL-2 therapy are uncommon (1.5% in 652 consecutive patients), the potential for significant myocardial ischemia or myocarditis exists, and careful monitoring for arrhythmias or myocardial failure is warranted. .A Kragel AH; Travis WD; Steis RG; Rosenberg SA; Roberts WC. .I 274552 .U 91003851 .S Cancer 9101; 66(7):1517-23 .M Adult; Aged; Antibodies, Viral/AN; Colorectal Neoplasms/IM/PA/*TH; Female; Human; Immunotherapy, Active/AE/*MT; Liver Neoplasms/SC; Lung Neoplasms/SC; Lymphatic Metastasis; Male; Middle Age; Neoplasm Staging; Newcastle Disease Virus/IM; Skin Tests; Support, Non-U.S. Gov't. .T Postoperative active specific immunization in colorectal cancer patients with virus-modified autologous tumor-cell vaccine. First clinical results with tumor-cell vaccines modified with live but avirulent Newcastle disease virus [published erratum appears in Cancer 1991 Apr 15;67(8):2124] .P JOURNAL ARTICLE. .W Sixteen patients with colorectal carcinoma Dukes' Stage B2, C, or D were treated with an autologous virus-modified tumor-cell vaccine after potential curative tumor resection (R0-Resection). An inoculum of 1 X 10(7) cells incubated with 32 hemagglutination units of nonirradiated Newcastle disease virus (NDV) was given intracutaneously up to four times at 10-day intervals. The delayed-type hypersensitivity (DTH) skin reaction was measured. The vaccination was well tolerated. In 11 of 16 patients an increasing reactivity against the vaccine was observed during the vaccination procedure. A challenge test using autologous tumor cells without NDV after the vaccination cycle revealed a specific antitumor sensibilization in 12 patients. The DTH response was not due to bacterial contamination or sensibility to the virus. Histologic examination of the vaccination site showed a dense infiltration of predominantly helper T-lymphocytes. We conclude that in most of the patients treated active, specific immunization led to a specific antitumor sensitivity. .A Bohle W; Schlag P; Liebrich W; Hohenberger P; Manasterski M; Moller P; Schirrmacher V. .I 274553 .U 91003852 .S Cancer 9101; 66(7):1524-8 .M Adult; Antigens, CD/AN; Base Sequence; Case Report; Diagnosis, Differential; DNA, Viral/AN; Female; Hodgkin's Disease/*DI; Human; HTLV-I/IP; HTLV-I Antibodies/AN; Immunoenzyme Techniques; Leukemia-Lymphoma, T-Cell, Acute, HTLV-I-Associated/*DI/GE/IM; Molecular Sequence Data; Polymerase Chain Reaction. .T Acute T-cell leukemia/lymphoma mimicking Hodgkin's disease with secondary HTLV I seroconversion. .P JOURNAL ARTICLE. .W The authors observed a pleiomorphic lymphoma mimicking Hodgkin's lymphoma in a French Guyana black woman lacking antibodies for human T-cell lymphoma/leukemia virus type I (HTLV I). After two courses of chemotherapy with either mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or doxorubicin, bleomycin, vincaleukoblastine, and dacarbazine (ABVD), a typical acute T-cell leukemia/lymphoma developed with HTLV I seroconversion. Specific HTLV I DNA sequences were detected using the polymerase chain reaction (PCR) on a lymph node biopsy obtained before chemotherapy. The mechanisms of the seroconversion are discussed. .A Picard F; Dreyfus F; Le Guern M; Tulliez M; d'Auriol L; Neron S; Galibert F; Saragosti S; Varet B. .I 274554 .U 91003853 .S Cancer 9101; 66(7):1529-33 .M Adenocarcinoma/*IM/SC; Antigens, Tumor-Associated, Carbohydrate/*BL; Human; Immunohistochemistry; Lymphatic Metastasis; Neoplasm Invasiveness; Portal System/*IM; Radioimmunoassay; Stomach Neoplasms/*IM. .T Immunohistochemical studies on the main entrance-route of CA19-9 into the peripheral venous blood of gastric cancer patients. Correlation with CA19-9 levels in peripheral and portal blood. .P JOURNAL ARTICLE. .W The correlation between CA19-9 levels of portal and peripheral venous blood, and immunohistochemical variables of cancer lesions was examined in 53 gastric cancer patients and eight patients with benign diseases. Immunohistochemically, CA19-9 was found in 33 (62.5%) of 53 primary lesions. The antigen was found in the cancer cells of invasive lymphatics and node metastases of every CA19-9 localized cancer, although the cancer cells in veins showed little or no CA19-9. There was little or no antigen in the cancer cells in veins, lymphatics, or metastases of 20 CA19-9 nonlocalized primary lesions. Patients with CA19-9 nonlocalized cancer or with benign diseases showed no elevation of the antigen levels in peripheral or portal blood. CA19-9 levels of portal blood (mean, 76.4 U/ml; positive rate, 33.3%) were not different from those of peripheral blood (mean, 91.5 U/ml; positive rate, 33.3%). Additionally, the antigen levels of the blood in patients with lymphatic invasion or node metastases were significantly higher than those in patients without the invasion or the metastases, and every patient without the invasion showed no elevation of the antigen. These results suggest that production of the antigen in cancer cells may be a premise of CA19-9 elevation in peripheral blood and that CA19-9 may be drained by the thoracic duct of the lymphatic system via node metastases or invasive lymphatics, but not by the hematogenous portal system. .A Tabuchi Y; Deguchi H; Imanishi K; Saitoh Y. .I 274555 .U 91003855 .S Cancer 9101; 66(7):1539-43 .M Aged; Biogenic Polyamines/*AN; Colonic Polyps/DI/*ME; Colorectal Neoplasms/DI/*ME; Female; Human; Intestinal Mucosa/ME; Male; Mass Screening/MT; Middle Age; Ornithine Decarboxylase/*ME; Precancerous Conditions/DI/*ME; Putrescine/AN; Spermidine/AN; Spermine/AN; Support, U.S. Gov't, P.H.S.; Tumor Markers, Biological/*AN. .T Colonic polyamine content and ornithine decarboxylase activity as markers for adenomas. .P JOURNAL ARTICLE. .W Polyamine content (putrescine, spermidine, and spermine) or ornithine decarboxylase (ODC) activity was measured in normal-appearing colonic mucosa from patients undergoing colonoscopy. Comparisons were made between those with and those without adenomatous polyps. Colonic mucosal polyamine content was measured in 44 persons. Mean putrescine content was 1.25 +/- 0.26 (SE) nmol/mg protein in 22 patients with adenomatous polyps compared with 0.53 +/- 0.12 nmol/mg protein in patients without polyps (P less than 0.02). Tissue content of spermidine and spermine did not differ between these two groups. Ornithine decarboxylase activity was measured in tissue from 45 patients. Mean ODC activity was 2.84 +/- 0.73 pmol/hr/mg protein in 23 persons with adenomatous polyps compared with 1.15 +/- 0.18 pmol/hr/mg protein in persons without polyps (P less than 0.05). Mucosal putrescine and ODC activity are elevated in patients with adenomatous polyps compared with patients without polyps. These biochemical markers may prove helpful in improving surveillance methods for colorectal cancer and premalignant adenomatous polyps. .A McGarrity TJ; Peiffer LP; Bartholomew MJ; Pegg AE. .I 274556 .U 91003856 .S Cancer 9101; 66(7):1544-51 .M Antigens, Surface/AN; Case Report; Cell Differentiation; Cell Division; Erythroid Progenitor Cells/*CY/DE/ME; Erythropoietin/ME/PD; Growth Substances/PD; Human; Karyotyping; Leukemia, Myeloid, Philadelphia-Positive/BL; Male; Middle Age; Receptors, Endogenous Substances/AN; Tumor Cells, Cultured/*CY/DE. .T Establishment of an erythroid cell line (JK-1) that spontaneously differentiates to red cells. .P JOURNAL ARTICLE. .W The authors established a new hemopoietic cell line (JK-1) from a patient with chronic myelogenous leukemia in erythroid crisis. This JK-1 line predominantly consists of immature cells, but a small number of mature erythroblasts and red cells can be consistently seen without any specific differentiation inducer. The JK-1 cells grow in suspension culture supplemented with human plasma and carry double Philadelphia chromosomes. Hemoglobin staining with benzidine was positive for about 20% of cells and the type of the hemoglobin was for the most part HbF. Surface-marker analysis revealed JK-1 cells positive for glycophorin A, EP-1, and HAE9. The proportion of mature cells was elevated by the addition of delta-aminolevulinic acid. Erythropoietin (EPO) enhanced the growth of JK-1 cells either in the suspension or in methylcellulose semisolid culture. The total number of EPO receptors was 940 per cell, of which 220 sites had an affinity higher than the other 720 sites. This is the first report of an established human erythroid cell line which spontaneously undergoes terminal differentiation. .A Okuno Y; Suzuki A; Ichiba S; Takahashi T; Nakamura K; Hitomi K; Sasaki R; Tada K; Imura H. .I 274557 .U 91003857 .S Cancer 9101; 66(7):1552-4 .M Adenocarcinoma/PA/SC; Axilla; Breast Neoplasms/PA; Colonic Neoplasms/PA; Human; Lymph Nodes/*PA; Lymphatic Metastasis/*PA; Mesentery; Necrosis; Rectal Neoplasms/PA. .T Regional differences in the intranodal distribution of tumor cells. .P JOURNAL ARTICLE. .W The intranodal distribution of tumor cells was examined in 103 mesenteric and 135 axillary nodes to determine the frequency of a circumferential type of distribution and its relationship, if any, to central necrosis. Eighteen percent of the mesenteric nodes removed at surgery from patients with colon cancer contained a circumferential rim of viable tumor cells in an area corresponding wholly or in part to the normal location of the marginal sinus. In each case this rim of tumor cells surrounded a large central area of necrosis. In contrast, only one of the 135 axillary nodes removed from patients with breast cancer demonstrated this pattern. These findings suggest that by interrupting blood and lymph vessels, the circumferential spread of tumor cells underlies development of central necrosis. Previously described structural dissimilarities between mesenteric and axillary nodes may explain the striking difference in incidence of this pattern in these nodes. .A Dumont AE; Harris MN; Vazquez M. .I 274558 .U 91003858 .S Cancer 9101; 66(7):1555-62 .M Adenoma/GE/SC; Adult; Alkaline Phosphatase/ME; Aneuploidy; Calcium/BL; Carcinoma/GE/SC; DNA, Neoplasm/*AN; Female; Flow Cytometry; Human; Lung Neoplasms/SC; Lymphatic Metastasis; Male; Middle Age; Parathyroid Neoplasms/BL/CL/*GE; Support, Non-U.S. Gov't. .T Flow cytometric DNA analysis of parathyroid tumors. Implication of aneuploidy for pathologic and biologic classification. .P JOURNAL ARTICLE. .W The previous cytometric studies on parathyroid tumors have provided conflicting data regarding the relationship between DNA content and histopathology, resulting from differences in technical methods and data analysis. This study measured nuclear DNA of parathyroid tumors by flow cytometry in fresh material and determined whether DNA aneuploidy really assists in making a pathologic diagnosis of carcinoma or not. From May 1987 through April 1989, 65 consecutive patients operated on for primary hyperparathyroidism had DNA analysis of the freshly excised parathyroid tumors. Three of the patients had metastatic lesions of parathyroid carcinoma in the lung, cervical lymph nodes, and lung and mediastinal lymph nodes, respectively. Pathologic classifications of the lesions from the other 62 patients were 54 adenomas, four carcinomas, and four hyperplasias. In all the latter patients, hyperplasia was associated with a multiple endocrine neoplasia syndrome. Unequivocal evidence of aneuploidy was found in all of the metastatic lesions and 60% of the primary lesions of the carcinomas, in 9% of the adenomas and in 50% of the hyperplasias. Therefore, parathyroid carcinomas were more apt to be aneuploid than were adenomas (P = 0.0015, both-sided testing). In each of the cases of aneuploid hyperplasia, a small aneuploid peak was found. The high incidence of aneuploidy in patients with multiple endocrine neoplasia type 1 may indicate the presence of clonal heterogeneity of hyperplastic glands and the presence of an abnormal subset of cells that have malignant potential. Cell distribution analysis did not provide any significant information beyond ploidy level. In conclusion, DNA flow cytometric analysis of DNA ploidy patterns is a valuable adjunct to the histopathologic diagnosis of parathyroid neoplasms. .A Obara T; Fujimoto Y; Kanaji Y; Okamoto T; Hirayama A; Ito Y; Kodama T. .I 274559 .U 91003859 .S Cancer 9101; 66(7):1563-7 .M Adenoma/DI; Biopsy/MT; Carcinoma in Situ/DI; Colonic Neoplasms/*DI/PA/SC; Colonic Polyps/DI; Cytodiagnosis/MT; Epithelium/PA; Human; Predictive Value of Tests; Reproducibility of Results; Retrospective Studies. .T Brush cytology in the diagnosis of colonic neoplasms. .P JOURNAL ARTICLE. .W During a three-year period (1986-1988), 234 colonic brush specimens were received in the authors' laboratory. Nine samples (4%) were deemed unsatisfactory for evaluation because of inadequate cellularity and/or poor fixation. In 11 cases concomitant or follow-up histologic specimens were not available. The remaining 214 specimens included 82 malignant neoplasms, 88 neoplastic polyps (adenomas), and 44 nonneoplastic lesions. Sixty-seven (82%) of malignant neoplasms were correctly diagnosed by brush cytology. Three cases of adenoma with severe dysplasia or in situ carcinoma were diagnosed as adenocarcinoma by cytology. No false-positive diagnoses were made of nonneoplastic lesions. Brush cytology was found to be a more sensitive technique in the diagnosis of colon cancer than endoscopic biopsy (82% and 74% sensitivity, respectively). The combination of the two techniques increased the sensitivity to 90% and improved the overall accuracy of the test. Seventy-one (82%) of the colonic adenomas were correctly diagnosed by cytology. Brush cytology is a convenient, safe, and accurate technique which should be used concurrently with endoscopic biopsy or polypectomy. .A Ehya H; O'Hara BJ. .I 274560 .U 91003860 .S Cancer 9101; 66(7):1568-77 .M Adolescence; Adult; Child; Child, Preschool; Combined Modality Therapy; Female; Follow-Up Studies; Human; Infant; Kidney Neoplasms/*PA/TH; Male; Neoplasm Staging; Nephrectomy; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Wilms' Tumor/*PA/TH. .T Pathologic delineation of the papillonodular type of cystic partially differentiated nephroblastoma. A review of 11 cases. .P JOURNAL ARTICLE. .W Eleven cases of a previously unrecognized papillonodular variant of cystic partially differentiated nephroblastoma (CPDN) are described. This type of CPDN has all the features of the conventional type of CPDN; however, in addition, there are grossly demonstrable papillonodular projections extending from the septa into the cyst lumina. The septa do not show any expansile tumor masses. Like most cases of the conventional type, this new type of CPDN was usually diagnosed in infants. Nephrectomy (total in 10 and partial in 1) was done in these cases. Additional chemotherapy with or without radiation therapy was given in seven cases. No recurrence was noted during the period extending from 21 months to 8 years in the eight cases in which follow-up data are available. Nephrectomy with regular follow-up visits for possible recurrence may be the management of choice. Pathologists should be aware of this variant of CPDN so that overtreatment can be avoided. The revised criteria for CPDN can be summarized as follows: (1) The discrete entirely cystic tumor contains luminal papillonodules in some cases. (2) Septa and the papillonodules, when present, are the only solid portion of the tumor and contain blastemal cells admixed with their normal and aberrant derivatives. (3) The tumor without and with papillonodules is classified as a conventional and papillonodular type of CPDN, respectively. .A Joshi VV; Beckwith JB. .I 274561 .U 91003861 .S Cancer 9101; 66(7):1578-89 .M alpha 1-Antichymotrypsin/AN; alpha 1-Antitrypsin/AN; Adolescence; Adult; Aged; Aged, 80 and over; Castor Bean; Child; Child, Preschool; Combined Modality Therapy; Desmin/AN; Female; Human; Immunohistochemistry; Lectins/AN; Male; Middle Age; Recurrence; Sarcoma/MO/*PA/TH; Soft Tissue Neoplasms/MO/*PA/TH; Support, Non-U.S. Gov't; Survival Rate. .T Soft tissue sarcoma with additional anaplastic components. A clinicopathologic and immunohistochemical study of 27 cases. .P JOURNAL ARTICLE. .W This clinicopathologic study concerns 27 cases of "dedifferentiated" soft tissue sarcoma (DSTS), including 14 liposarcomas, six leiomyosarcomas, five chondrosarcomas, and two rhabdomyosarcomas. In addition, the authors conducted an immunohistochemical survey of 23 cases and an electron microscopic examination of three. The findings were compared with observations of 32 cases of de novo malignant fibrous histiocytoma (MFH). All tumors contained additional distinct anaplastic portions indistinguishable from MFH under conventional light microscopy, ultrastructurally, and in cases of immunoreactivity for alpha-1-antichymotrypsin and alpha-1-antitrypsin and on lectin histochemical findings for ricinus communis agglutinin and concanavalin agglutinin. The desmin reactivity present in anaplastic portions of 14 DSTS and in eight de novo MFH is taken to mean that myofibroblasts are present in these tumors. The anaplastic components of DSTS are presumed to represent the proliferation of another clone of undifferentiated mesenchymal cells that fail to differentiate along any specific lineage other than fibroblast-like cells, histiocyte-like cells, and myofibroblasts. Nineteen patients died of tumor and four are alive and well 1.6, 1.7, 2.1, and 5.2 years after the initial treatment, respectively. .A Hashimoto H; Daimaru Y; Tsuneyoshi M; Enjoji M. .I 274562 .U 91003862 .S Cancer 9101; 66(7):1590-5 .M Administration, Oral; Cancer Care Facilities; Female; Follow-Up Studies; Human; India; Male; Morphine/*AD/AE; Neoplasms/*CO; Pain Measurement; Pain, Intractable/*DT/ET/PP; Palliative Treatment/*; Prospective Studies. .T Continuing care for cancer pain relief with oral morphine solution. One-year experience in a regional cancer center. .P JOURNAL ARTICLE. .W This report is a prospective study of 223 patients with intractable cancer pain who were offered continuing care during the year 1988 at the Pain Relief Unit, Kidwai Memorial Institute of Oncology, Bangalore, India, with a minimum follow-up of 4 months and a maximum follow-up of 16 months. A high percentage of pain relief was attained within a mean duration of 4 days, which on follow-up was maintained at a steady level in most patients (91.1%). Oral morphine could not be continued in three patients because of vomiting. The main side effects noticed were nausea and vomiting, itching, and constipation. At any time during the first 140 days, only 30% of patients had side effects and appropriate medication successfully managed these side effects. During the rest of the study period, the side effects were minimal. Oral morphine used with proper adjuncts offers the best pain palliation in most patients, with minimal side effects. .A Vijayaram S; Ramamani PV; Chandrashekhar NS; Sudharshan R; Heranjal R; Lobo B; Obedullah D; Bhargava MK. .I 274563 .U 91003863 .S Cancer 9101; 66(7):1596-600 .M Analysis of Variance; Female; Human; Male; Melanoma/*MO; Models, Statistical; Multivariate Analysis; Prognosis; Support, Non-U.S. Gov't; Survival Rate; Uveal Neoplasms/*MO. .T Clinical prognostic factors in patients with posterior uveal malignant melanoma. .P JOURNAL ARTICLE. .W The authors evaluated the prognostic value of clinically assessed variables for predicting length of survival until death from metastatic disease in 237 patient with a primary choroidal or ciliary body melanoma. Using multivariate Cox proportional hazards modeling, the authors identified the largest linear basal tumor diameter (mm), estimated by indirect ophthalmoscopy and fundus drawing, the location of the anterior margin of the tumor relative to the ocular equator and ora serrata, and the age of the patient at the time of treatment as the best combination of the clinically assessed variables for predicting survival. For each patient in this group, the authors computed a prognostic index based on the best multivariate Cox model. They showed that patients with low, intermediate, and high values of prognostic index had low, intermediate, and high melanoma-related mortality rates, respectively, during the first 5 to 8 posttreatment years. These results suggest that: (1) clinically assessed variables evaluated according to a standardized protocol are useful for predicting the survival of treated patients with posterior uveal melanoma and (2) ophthalmologists who assess potential clinical prognostic variables consistently may identify subgroups of patients with comparable mortality risk on the basis of noninvasive testing. .A Augsburger JJ; Gamel JW. .I 274564 .U 91003865 .S Cancer 9101; 66(7):1613-20 .M Adult; Aged; Attitude to Health; Breast Neoplasms/*PC; Female; Health Behavior; Human; Mammography/EC/*MT; Mass Screening/*IS; Middle Age; Risk Factors; Support, Non-U.S. Gov't. .T Mammographic screening of women with increased risk of breast cancer. .P JOURNAL ARTICLE. .W Five hundred one women from Dallas County, Texas who participated in the American Cancer Society 1987 Texas Breast Screening Project were selected because of a self-reported family history of breast cancer (cases). They were matched with 501 randomly selected women from the same county with no family history (controls). Although there was a statistically significant trend with age for an increasing proportion of women to report having undergone mammography, there was no significant difference when comparing mammographic histories of cases with controls after controlling for age (31.5% versus 35.1%, P = 0.33). Significantly more cases (79%) perceived their risk for breast cancer to be moderate or greater compared with controls (54%, P less than 0.0001), but mammographic histories were not different when controlling for perceived risk. Both cases and controls cited lack of physician referral and cost as their reasons for not having undergone mammography. Women at increased risk for breast cancer (because of their family history) are not undergoing regular mammographic screening despite their self-awareness of the increase in their risk. .A Vogel VG; Graves DS; Vernon SW; Lord JA; Winn RJ; Peters GN. .I 274565 .U 91003866 .S Cancer 9101; 66(7):1621-9 .M Adult; Age Factors; Antineoplastic Agents, Combined/TU; Breast Neoplasms/DT/*MO/SU; Clinical Protocols; Combined Modality Therapy; Cyclophosphamide/TU; Female; Follow-Up Studies; Human; Multivariate Analysis; Neoplasm Metastasis; Ovariectomy; Receptors, Estrogen/AN; Risk Factors; Support, U.S. Gov't, P.H.S.; Survival Rate. .T Survival of premenopausal women with metastatic breast cancer. Long-term follow-up of Eastern Cooperative Group and Cancer and Leukemia Group B studies. .P CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL. .W In premenopausal women with metastatic breast cancer, differences in survival curves early during follow-up can be misleading. The authors therefore analyzed long-term survival in 378 patients, entered in three randomized trials, started between 1973 and 1978. Combined data from the three trials were used to increase the power for identifying prognostic variables. Cancer and Leukemia Group B (CALGB) trial 7382 randomized patients to oophorectomy plus either cyclophosphamide or combination chemotherapy or observation. Eastern Cooperative Oncology Group (ECOG) 2174 randomized patients who had not progressed 3 months after oophorectomy to combination chemotherapy or combination chemotherapy or observation. Trial ECOG 2177 randomized estrogen receptor (ER) positive or ER-unknown patients to oophorectomy plus combination chemotherapy or immediate combination chemotherapy, and ER-negative patients were directly assigned to combination chemotherapy. Hence ER-negative patients need not have been healthy enough to be randomized to oophorectomy. With only 14% of the patients still alive, median survival on the three studies was 30, 24, and 28 months. The median survival of individual treatments changed noticeably in ECOG 2174 and ECOG 2177 with long-term follow-up. At this time there are no differences in survival between randomized regimens in any of the three trials. In a multivariate model, factors associated with significantly poorer survival were visceral-dominant disease, nodal metastases, breast metastases, age younger than 45 years, ER negativity, and not receiving chemotherapy immediately after oophorectomy. This treatment difference was thus not due to imbalances in the prognostic variables used in the model, but it may be due to imbalances of unknown prognostic factors or differences in patient selection. .A Falkson G; Gelman RS; Leone L; Falkson CI. .I 274566 .U 91003867 .S Cancer 9101; 66(7):1630-5 .M Adenocarcinoma/MO/PA; Bladder/*PA; Bladder Neoplasms/MO/*PA; Carcinoma, Squamous Cell/MO/PA; Carcinoma, Transitional Cell/MO/PA; Cystoscopy; Female; Human; Male; Prognosis; Survival Rate. .T Analysis of bladder carcinoma by subsite. Cystoscopic location may have prognostic value. .P JOURNAL ARTICLE. .W Nine hundred fourteen cases of carcinoma of the urinary bladder registered from 1977 to 1988 with the Kansas state tumor registry were evaluated by subsite for differences in grade, histology, sex, age at diagnosis, and survival. Only initial occurrences of carcinoma were included. Carcinoma of the lateral walls accounted for 37.1%; the posterior wall, 17.9%; the trigone, 12.6%; the neck, 11.1%; the ureteric orifices, 9.8%; the dome, 7.7%; and the anterior wall, 3.8%. Malignant neoplasms occurring in the neck of the bladder had a significantly poorer prognosis by survival analysis (P less than 0.05). Malignancies of the dome were found to present as higher grade lesions (P = 0.00003), and carcinoma of the ureteric orifices and lateral walls tended to be of lower grade (P = 0.02 and P = 0.05, respectively). Carcinomas of the anterior wall and dome occurred in a more elderly population (mean ages, 75.6 and 73.9 years, respectively), and carcinomas of the trigone and ureteric orifices occurred in a younger group (mean ages, 68.3 and 67.5 years, respectively). On histologic evaluation the trigone gave rise to more squamous cell carcinoma than expected (P = 0.001, 325% of expected). No distribution difference was noted among subsites with respect to sex. These data show significant differences among subsites of the urinary bladder with regard to survival, grade, histology, and age at diagnosis. .A Stephenson WT; Holmes FF; Noble MJ; Gerald KB. .I 274567 .U 91003868 .S Cancer 9101; 66(7):1636-40 .M Adult; Aged; Antineoplastic Agents, Combined/TU; Appendiceal Neoplasms/CO; Combined Modality Therapy; Female; Human; Middle Age; Ovarian Neoplasms/CO; Pseudomyxoma Peritonei/ET/PA/*TH; Reoperation. .T The management of pseudomyxoma peritonei. .P JOURNAL ARTICLE. .W The management of nine patients with pseudomyxoma peritonei was reviewed. Aggressive surgical resection of tumor is the standard of treatment, with many patients requiring multiple laparotomies. Chemotherapy, including the use of cisplatin is not effective. Long-term nutritional support provides a better quality of survival for select patients. .A Mann WJ Jr; Wagner J; Chumas J; Chalas E. .I 274568 .U 91003869 .S Cancer 9101; 66(7):1641-8 .M Adolescence; Amputation; Bone Neoplasms/*DI/ET/SU; Child; Child, Preschool; Chondrosarcoma/*DI/ET/SU; Enchondromatosis/CO; Exostoses, Multiple Hereditary/CO; Female; Femoral Neoplasms/DI; Human; Humerus/PA/RA; Male; Neoplasm Recurrence, Local; Prognosis; Tibia/PA/RA. .T Chondrosarcoma of bone in children. .P JOURNAL ARTICLE. .W Chondrosarcoma of bone rarely occurs in children. This report analyzes the clinicopathologic features in a series of 47 patients with conventional chondrosarcoma who were less than 17 years of age. Of the 47 cases, 14 were from the Mayo Clinic files, and 33 were from our consultation files. Most of the lesions occurred in the trunk and upper ends of the long bones, with the humerus being the most frequent skeletal site. Twelve of the 47 tumors were secondary. The radiographic findings were the same as those seen in adult chondrosarcoma. Pathologically, the tumors were low grade. En bloc resection is the treatment of choice because of the high incidence of local recurrence with lesser surgical margins. Prognosis in childhood chondrosarcoma is no different from that in adult chondrosarcoma. None of the patients with follow-up data had metastasis. .A Young CL; Sim FH; Unni KK; McLeod RA. .I 274569 .U 91003870 .S Cancer 9101; 66(7):1649-53 .M Adult; Aged; Antineoplastic Agents/*AE; Avoidance Learning/*; Female; Food Habits/*PX; Human; Longitudinal Studies; Male; Middle Age; Nausea/CI/*PX; Scapegoating/*; Support, Non-U.S. Gov't. .T The scapegoat effect on food aversions after chemotherapy. .P JOURNAL ARTICLE. .W The effects of consuming a novel food (halva) versus a familiar food (cookies) before gastrointestinal (GI) toxic chemotherapy on patients' preference for familiar foods consumed after chemotherapy treatment were compared. The development of aversions to the novel and familiar foods was also assessed. Patients with a history of posttreatment nausea consumed either a novel or a familiar food before chemotherapy and were asked to keep a food record through the next breakfast and to rate their preference for these foods. Patients who consumed halva before treatment were significantly more likely to increase their ratings for foods consumed after chemotherapy than patients who consumed familiar cookies. Aversions to the novel food were significantly more frequent than aversions to the familiar food. These findings provide evidence that a novel but not a familiar food consumed before chemotherapy can act as a scapegoat to prevent items in the regular diet consumed after chemotherapy from decreasing in preference. Providing patients with a novel food before chemotherapy is a useful clinical intervention to reduce the likelihood of forming aversions to familiar foods consumed after chemotherapy. .A Andresen GV; Birch LL; Johnson PA. .I 274570 .U 91003871 .S Cancer 9101; 66(7):1654-60 .M Adult; Aged; Blacks/*; Comparative Study; Female; Human; Income; Male; Middle Age; Neoplasms/*EH/MO; New York/EP; Socioeconomic Factors; Survival Rate; United States/EP. .T Cancer mortality in a higher-income black population in New York State. Comparison with rates in the United States as a whole. .P JOURNAL ARTICLE. .W In the 1980 Census the median family income among blacks in Suffolk County, New York (i.e., $19,604) was much higher than that for American blacks as a whole (i.e., $12,618) and 94.1% of that for American whites (i.e., $20,840), but the proportion below the poverty level was still higher for Suffolk County blacks than for American whites. Observed numbers of deaths from 1979 to 1985 for total cancers and most cancer sites in Suffolk County black men and women were not lower than expected on the basis of age-specific and gender-specific death rates for blacks in the US. Although numbers of deaths from cervical cancer and prostate cancer were slightly lower than expected in Suffolk County blacks versus American blacks, these numbers were still significantly greater than expected on the basis of death rates among American whites. Age-specific death rates for age groups 25 to 44 years to 55 to 64 years tended to be lower in Suffolk County for lung cancers in black men but not for breast cancer in black women. Specific cancer sites, which differ in the direction of the association between incidence and socioeconomic status, age, and gender must be considered in comparisons of cancer mortality by race and socioeconomic level. Implications of the comparisons were discussed with regard to the goal of reducing racial differences in cancer death rates. .A Polednak AP. .I 274571 .U 91003872 .S Cancer 9101; 66(7):1661 .M Aged; Breast Neoplasms/*TH; Combined Modality Therapy; Female; Human; Radiotherapy Dosage; Tamoxifen/*AE; Uterine Neoplasms/*CI/PA. .T Tamoxifen as a risk factor for endometrial cancer [letter; comment] .P COMMENT; LETTER. .A Hardell L. .I 274572 .U 91003873 .S Cancer 9101; 66(8):1663-70 .M Adult; Aged; Antibodies, Monoclonal/*DU; Breast Neoplasms/*CH/MO/PA/TH; Female; Hormones/TU; Human; Immunohistochemistry; Menopause; Middle Age; Predictive Value of Tests; Prospective Studies; Receptors, Estrogen/*AN; Receptors, Progesterone/*AN; Support, U.S. Gov't, P.H.S.; Survival Analysis. .T Immunocytochemical estrogen and progestin receptor assays in breast cancer with monoclonal antibodies. Histopathologic, demographic, and biochemical correlations and relationship to endocrine response and survival. .P JOURNAL ARTICLE. .W Breast cancer specimens from 600 women were assayed for estrogen receptors (ER) using an immunocytochemical assay (ICA) employing the monoclonal antiestrophilin antibody H222 Sp gamma. Results showed significant correlation with biochemical ER determinations as well as with tumor grade and menopausal status. In 449 cases, results of progesterone receptor assay by ICA using the monoclonal anti-PgR antibody KD 68, also correlated significantly with biochemical PgR measurements. The ERICA/PgRICA positivity was significantly more frequent in postmenopausal white women. Colloid carcinomas were most likely to be ERICA positive and PgRICA positive whereas medullary carcinomas were most often negative. In 47 patients with advanced mammary carcinoma, results of ERICA and PgRICA were more closely related to endocrine response than those of ER and PgR by dextran-coated charcoal assay (DCC). In 339 women with Stage I or Stage II breast cancer, ERICA was significantly associated with disease-free survival. Analysis by Cox's proportional hazard model, however, showed PgRICA to be the best predictor of survival and disease-free survival in 197 women at the same stages of disease. These data indicate that ICA is more predictive of prognosis than biochemical ER and PgR. The ease of ICA performance coupled with these results indicate that the method is an acceptable substitute for DCC in analyzing breast cancers for ER/PgR. .A Pertschuk LP; Kim DS; Nayer K; Feldman JG; Eisenberg KB; Carter AC; Rong ZT; Thelmo WL; Fleisher J; Greene GL. .I 274573 .U 91003874 .S Cancer 9101; 66(8):1671-7 .M Adolescence; Antineoplastic Agents, Combined/AE/*TU; Child; Child, Preschool; Cytarabine/AD/AE; Female; Human; Hydrocortisone/AD; Infant; Infusions, Intravenous; Leukemia, Lymphocytic, Acute, L1/*DT; Male; Methotrexate/AD; Pilot Projects; Remission Induction; Support, U.S. Gov't, P.H.S.; Teniposide/AD/AE; United States. .T Teniposide (VM-26) and continuous infusion cytosine arabinoside for initial induction failure in childhood acute lymphoblastic leukemia. A Pediatric Oncology Group pilot study. .P CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY. .W Twenty-six evaluable children with newly diagnosed acute lymphoblastic leukemia (ALL) who failed to achieve initial remission after receiving two to seven drugs for at least a 4-week period were given teniposide (VM-26) and continuous infusion cytosine arabinoside (Ara-C). Twenty-two received 150 mg/m2 of VM-26 on days 1 and 2 with 100 mg/2 of Ara-C as a continuous infusion on days 1 through 5; a second shortened course was given on day 14 to eight patients who had evidence of some antileukemic effect or were clinically judged able to tolerate a second course. The last four patients received three daily doses of VM-26 and a 7-day infusion of Ara-C at the same daily dosages. Twelve (48%) achieved complete remission (CR) of ALL. There was a trend toward decreasing response rates with an increasing number of drugs used in the initial induction regimen, i.e., five CR among seven patients with a prior two-drug induction attempt, six CR among 14 patients with a prior three- to four-drug induction attempt, and one CR among four patients with a prior five- to seven-drug induction attempt (P = 0.14). Ten of 17 non-T-cell patients and two of nine T-cell patients achieved remission (P = 0.10). The median time required to achieve a complete remission from the initiation of treatment was 26 days (range, 14-72 days). This period was shorter in those who required one course compared with those who required two induction courses, i.e., 25 days median vs. 44 days median. Toxicity was significant and due mainly to marrow aplasia and infection; one patient had severe prolonged VM-26-induced hypotension. Of the 12 patients entering remission, two were removed for marrow transplant and one was removed due to parental request. In the remaining nine patients, median remission duration was only 2 months (range, 1-18 months). All nine patients relapsed in the marrow. Among the entire group of 26 patients, only one patient is alive and a long-term event-free survivor (after allogeneic marrow transplant). Due to the current use of more aggressive initial induction regimens and the extremely poor prognosis in children who fail to achieve initial remission, more intensive regimens of continuation therapy or alternative therapies, such as bone marrow transplant, should be considered. .A Ochs J; Rivera GK; Pollock BH; Buchanan G; Crist W; Freeman AI. .I 274574 .U 91003875 .S Cancer 9101; 66(8):1678-84 .M Antineoplastic Agents, Combined/*TU; Breast Neoplasms/*DT/MO/SU; Combined Modality Therapy; Cyclophosphamide/AD; Data Interpretation, Statistical; Dose-Response Relationship, Drug; Female; Fluorouracil/AD; Human; Levamisole/AD; Menopause; Methotrexate/AD; Retrospective Studies; Support, U.S. Gov't, P.H.S.; Survival Analysis. .T Association of disease-free survival and percent of ideal dose in adjuvant breast chemotherapy. .P CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL. .W The relationship between percent of ideal dose and disease-free survival was examined in 256 Stage II and III patients who participated in a 2-year breast adjuvant chemotherapy trial consisting of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) given postoperatively. When analyzed analogously to previous work, the results confirmed a dose-response relationship: that is, there appeared to be an improved disease-free survival for patients receiving higher doses of adjuvant chemotherapy. The major criticism of such an analysis is its bias. This bias was addressed by considering only patients who were still receiving therapy at 6, 12, and 24 months; then, the dose-response relationship was no longer seen. Although causality cannot be inferred, the apparent differences in disease-free survival among the dose groups can be attributed to recurrences in the first 2 years among patients receiving lower doses of chemotherapy. .A Geller NL; Hakes TB; Petroni GR; Currie V; Kaufman R. .I 274575 .U 91003876 .S Cancer 9101; 66(8):1685-7 .M Doxorubicin/AD/*TU; Drug Therapy, Combination; Female; Hepatoma/*DT; Human; Liver Neoplasms/*DT; Male; Middle Age; Prospective Studies; Support, Non-U.S. Gov't; Verapamil/AD/*TU. .T Doxorubicin for unresectable hepatocellular carcinoma. A prospective study on the addition of verapamil. .P CLINICAL TRIAL; JOURNAL ARTICLE. .W A prospective study was conducted to assess the safety and efficacy of the addition of oral verapamil to intravenous Adriamycin (doxorubicin) for the management of patients with unresectable hepatocellular carcinoma (HCC). All 28 patients studied had histologically verified disease, and cirrhosis was present in 20 of the 21 patients with adequate tissue sampling. The overall median survival was 57 days. Chemotherapy was terminated in seven patients after one course of treatment. Partial response and complete response were noted in four patients (19%) and one patient (4.8%), respectively, among the 21 patients evaluated. Side effects related to the chemotherapy were present in all patients studied. Death from fulminating sepsis occurred in three of the 13 patients with leukopenia. Symptomatic myocardial dysfunction developed in one patient. The addition of verapamil apparently did not potentiate the tumoricidal effect of systemic Adriamycin on HCC but probably did increase its complications. .A Lai EC; Choi TK; Cheng CH; Mok FP; Fan ST; Tan ES; Wong J. .I 274576 .U 91003877 .S Cancer 9101; 66(8):1688-91 .M Adenocarcinoma/*DT; Adult; Aged; Antineoplastic Agents, Combined/AE/*TU; Carcinoma, Squamous Cell/*DT; Cisplatin/AD/AE; Dose-Response Relationship, Drug; Drug Evaluation; Female; Fluorouracil/AD/AE; Human; Male; Middle Age; Saline Solution, Hypertonic; Support, U.S. Gov't, P.H.S.. .T A phase I trial of cisplatin in hypertonic saline and escalating doses of 5-fluorouracil by continuous intravenous infusion in patients with advanced malignancies. .P JOURNAL ARTICLE. .W Thirty-four patients with incurable solid tumors were treated in a Phase I trial with a fixed dose of high-dose cisplatin (CDDP) administered in hypertonic saline and escalating doses of infusional 5-fluorouracil (5-FU). Five treatment levels of 5-FU, ranging from 500 to 900 mg/m2/day for 5 days, were studied. Leukopenia, thrombocytopenia, and oral mucositis were the dose-limiting toxicities encountered. Nephrotoxicity was minimal. Ototoxicity and peripheral neuropathies were rare and mild in this patient group, but most patients received only a small number of treatment cycles. Diarrhea was not dose-limiting. Two complete responses (one non-small cell lung cancer and one sweat gland carcinoma) were observed. No other major responses were noted. With the dose of CDDP set at 35 mg/m2/day for 5 consecutive days, the maximum tolerated dose (MTD) of a concurrent 5-day 5-FU infusion was found to be 900 mg/m2/day. The recommended dosages for Phase II trials are 35 mg/m2/day CDDP and 800 mg/m2/day 5-FU for 5 consecutive days. Cancers of the lung, breast, gastrointestinal tract, and genitourinary tract would be reasonable targets for Phase II studies. .A Saltz L; Kelsen D. .I 274577 .U 91003878 .S Cancer 9101; 66(8):1692-6 .M Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Combined/AE/*TU; Bleomycins/AD/AE; Carcinoma, Squamous Cell/*DT/RT/SU; Child; Cisplatin/AD/AE; Combined Modality Therapy; Female; Fluorouracil/AD/AE; Human; Lip Neoplasms/*DT/RT/SU; Male; Middle Age; Skin Neoplasms/*DT/RT/SU. .T Treatment of advanced squamous cell carcinoma of the skin with cisplatin, 5-fluorouracil, and bleomycin. .P JOURNAL ARTICLE. .W The authors treated 14 patients with advanced squamous cell carcinoma (SCC) of the skin or lip with one to four cycles of combination chemotherapy consisting of cisplatin by bolus injection, and 5-fluorouracil (5-FU) and bleomycin by continuous 5-day infusion. Objective responses were seen in 11 of the 13 evaluable patients (84%). Four patients had a complete remission (30%) and seven patients, a partial remission (54%). Local control after definitive complementary radiation and/or surgical treatment was achieved in seven patients. Toxic side effects was acceptable; they consisted of nausea and vomiting in all patients, transient skin changes, hematologic (Grade 3/4) abnormalities in four patients, and pulmonary fibrosis in one elderly patient. These results show that this chemotherapy combination could play a role in reducing the tumor mass and in facilitating definitive treatment to obtain better functional and cosmetic results in advanced SCC of the skin. .A Sadek H; Azli N; Wendling JL; Cvitkovic E; Rahal M; Mamelle G; Guillaume JC; Armand JP; Avril MF. .I 274578 .U 91003880 .S Cancer 9101; 66(8):1703-10 .M Adolescence; Antineoplastic Agents, Combined/*TU; Bone Neoplasms/*DT/PA/SU; Cisplatin/AD/AE; Combined Modality Therapy; Comparative Study; Doxorubicin/AD/AE; Female; Human; Ifosfamide/AD/AE; Infusions, Intra-Arterial; Infusions, Intravenous; Male; Methotrexate/AD/AE; Osteosarcoma/*DT/PA/SU; Support, Non-U.S. Gov't. .T Effect of intraarterial versus intravenous cisplatin in addition to systemic doxorubicin, high-dose methotrexate, and ifosfamide on histologic tumor response in osteosarcoma (study COSS-86). .P CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY. .W In osteosarcoma, intraarterial (IA) administration of systemic treatment has been advocated to improve local tumor response preparing for, or even obviating, definitive surgery. Because data from the literature did not unequivocally support the local superiority of IA infusion, a comparative study was started in 1986. Preoperative chemotherapy consisted of 45 mg/m2 of doxorubicin on days 1 and 2; 12 g/m2 of high-dose methotrexate on days 15 and 22; and 3 g/m2 of ifosfamide on days 29, 30, 50, and 51 followed on days 31 and 52 by intravenous (IV) versus IA tourniquet infusion of cisplatin (DDP). A strict randomization of patients was not feasible. A balanced distribution of risk factors was strived for by stratifying and allocating the appropriate patients centrally. The infusion time was prolonged from 1 to 5 hours in the IV group, and the DDP dose was reduced from 150 to 120 mg/m2 in both arms when intolerable ototoxicity became apparent. A multivariate analysis was performed to exclude a bias on the response rates from risk factor distribution and from modifications of DDP infusion time and dosage. The overall fraction of histologic good responders (greater than 90% necrosis) was not found to be different after IA versus IV treatment (34/50 [68%] vs. 41/59 [69%]). Intraarterial instead of IV use of DDP within an aggressive systemic treatment does not seem to improve the local tumor response. .A Winkler K; Bielack S; Delling G; Salzer-Kuntschik M; Kotz R; Greenshaw C; Jurgens H; Ritter J; Kusnierz-Glaz C; Erttmann R; et al. .I 274579 .U 91003881 .S Cancer 9101; 66(8):1711-6 .M Carcinoma, Squamous Cell/*EP/PA; Case-Control Studies; Female; Human; Hypopharyngeal Neoplasms/*EP/PA; Italy/EP; Laryngeal Neoplasms/*EP/PA; Male; Middle Age; Support, Non-U.S. Gov't. .T Topographic classification, clinical characteristics, and diagnostic delay of cancer of the larynx/hypopharynx in Torino, Italy. .P JOURNAL ARTICLE. .W The case series of a population-based case-control study of laryngeal and hypopharyngeal cancers in Torino, Italy, included 281 men with clinical and anamnestic data. Two hundred fifteen, 28, and 38 cancers originated from the endolarynx, epilarynx, and hypopharynx, respectively. Regions invaded by the tumor were divided into 26 subsites. A classification based on the number of invaded subsites was proposed, which agreed well with the T classification of the TNM system. Cancers originating from the hypopharynx invaded more subsites than cancers from the endolarynx, and among the latter, supraglottic were more invasive than glottic lesions. The number of invaded subsites was strongly associated with nodal involvement. Among symptoms at onset of disease and at diagnosis, patients with endolaryngeal lesions reported dysphonia and dyspnea more frequently, and patients with lesions from other regions had a higher prevalence of dysphagia, odynophagia, otalgia, and adenopathia. Clinical and epidemiologic results of this study suggest considering the endolarynx, epilarynx, and hypopharynx as separate anatomic entities. Diagnostic delay was not associated with tumor size and showed a negative trend with involvement of cervical lymph nodes, suggesting that stage at diagnosis is due to intrinsic differences in tumor aggressiveness. .A Merletti F; Faggiano F; Boffetta P; Lehmann W; Rombola A; Amasio E; Tabaro G; Giordano C; Terracini B. .I 274580 .U 91003882 .S Cancer 9101; 66(8):1717-20 .M Actuarial Analysis; Adenocarcinoma/MO/PA/*SU; Adult; Aged; Aged, 80 and over; Common Bile Duct Neoplasms/MO/PA/*SU; Comparative Study; Duodenum/SU; Female; Follow-Up Studies; Human; Male; Middle Age; Pancreatectomy; Pancreatic Neoplasms/MO/PA/SU; Survival Analysis; Vater's Ampulla/*. .T Long-term follow-up of 24 patients undergoing radical resection for ampullary carcinoma, 1953 to 1988. .P JOURNAL ARTICLE. .W Potentially curative radical pancreaticoduodenectomy for ampullary adenocarcinoma was performed in 24 patients over a 35-year period. The overall operative mortality was 12.5%. Actuarial survival rate at 5 years was 61% +/- 13.4 standard error of the mean (SEM) and subsequently remained unchanged. In the same time period, 21 patients underwent potentially curative radical pancreaticoduodenectomy for periampullary tumors of pancreatic origin. Similar analysis showed an overall operative mortality of 23.8% and a survival rate at 5 years of 27% +/- 12.5 SEM. The results of radical pancreaticoduodenectomy for ampullary carcinoma in the most recent years (1976 to 1988) were compared with those of former years (1953 to 1975). There were no statistically significant differences in the 5-year survival rate; however, the operative mortality decreased from 25% in the former period to 6.3% in the recent period. Survival was dependent on nodal status. The 5-year survival rate was 78% +/- 11.5 SEM in the absence of nodal metastasis versus 50% +/- 25 SEM in the presence of regional nodal metastasis. These findings support the concept that radical pancreaticoduodenectomy offers a realistic probability for cure in a selected group of patients with carcinomas of the ampulla of Vater. .A Shutze WP; Sack J; Aldrete JS. .I 274581 .U 91003883 .S Cancer 9101; 66(8):1721-5 .M Adolescence; Adult; Age Factors; Aged; Aged, 80 and over; Breast Neoplasms/EH/EP/PA/*RA; Calcinosis/EH/EP/PA/*RA; Female; Fibrocystic Disease of Breast/EH/EP/PA/*RA; Human; Mammography; Middle Age; New Mexico/EP; Precancerous Conditions/EH/EP/PA/*RA; Predictive Value of Tests; Support, U.S. Gov't, P.H.S.. .T Radiographic microcalcification and parenchymal patterns as indicators of histologic "high-risk" benign breast disease. .P JOURNAL ARTICLE. .W Breast tissue from a forensic autopsy series of 486 women (15 to 98 years of age) was studied radiographically and by histologic sampling. Prevalence of Wolfe P2/Dy parenchymal patterns decreased with age. Radiographic nonvascular microcalcification and histologic presence of marked ductal epithelial hyperplasia and lobular microcalcification increased with age. Both of these histologic parameters of increased risk for breast cancer correlated with the presence of radiographic microcalcification and Wolfe P2/Dy parenchymal pattern. The predictive value of the radiographic parameters for presence of "high-risk" proliferative fibrocystic change increased with age. .A Bartow SA; Pathak DR; Mettler FA. .I 274582 .U 91003884 .S Cancer 9101; 66(8):1726-31 .M Adult; Blotting, Southern; Carcinoma, Squamous Cell/*MI/PA; Case Report; Cyclosporins/TU; DNA Probes, HPV/DU; DNA, Viral/AN; Heart Transplantation/*; Human; Male; Oropharyngeal Neoplasms/*MI/PA; Papillomaviruses/GE/*IP; Postoperative Complications/*MI/PA; Prednisone/TU. .T Human papillomavirus type 16 associated with oral squamous carcinoma in a cardiac transplant recipient. .P JOURNAL ARTICLE. .W Human papillomavirus type 16 (HPV 16) has been associated with a variety of squamous carcinomas, particularly those involving the anogenital tract. The authors report the development of an oropharyngeal carcinoma in a 43-year-old man approximately 20 months after cardiac transplantation while he was on a maintenance regimen of cyclosporine A and prednisone. The carcinoma was resistant to treatment, and he died of complications related to metastatic disease 3 years posttransplantation. Molecular biologic studies using nonisotopic-labeled viral DNA probes were done. In situ hybridization demonstrated the presence of HPV 16 DNA in the tumor cells. DNA dot blot analysis confirmed the presence of multiple copies of HPV 16 DNA within the tumor cells and their absence from adjacent normal-appearing tissue. Southern blot analysis suggested that the HPV 16 DNA was integrated into the tumor cell genome. With increasing recognition of the carcinogenicity of HPV type 16 infection, a role for this virus in the development of squamous cell malignancies in immunosuppressed organ transplant recipients is likely to be noted with increasing frequency. .A Demetrick DJ; Inoue M; Lester WM; Kingma I; Duggan MA; Paul LC. .I 274583 .U 91003885 .S Cancer 9101; 66(8):1732-7 .M Antibodies, Monoclonal/DU; Antigens, CD/*BI/IM; Antigens, Differentiation/*BI/IM; Antigens, Neoplasm/*BI/IM; Diagnosis, Differential; Human; Immunohistochemistry; Mesenchymoma/DI/*IM/ME; Sarcoma/DI/*IM/ME; Support, Non-U.S. Gov't. .T Expression of Ki-1 antigen (CD30) in mesenchymal tumors. .P JOURNAL ARTICLE. .W Expression of CD30(Ki-1) antigen has long been considered to be restricted to activated lymphocytes and related tumors. However, expression of this antigen has also been detected in embryonal carcinomas, in nonembryonal carcinomas, in malignant melanomas, and even in some myeloid cell lines and macrophages at late stages of differentiation. In this study, using monoclonal antibody Ki-1, expression of CD30 antigen was immunohistochemically examined in frozen sections of 28 benign and 63 malignant mesenchymal tumors. The authors found CD30 expressed in two of four leiomyomas, seven of 11 leiomysarcomas, one of six rhabdomyosarcomas, two of two aggressive fibromatoses, one of three fibrosarcomas, two of four synovial sarcomas, one giant cell tumors of tendon sheaths, all five malignant fibrous histiocytomas, all three osteosarcomas, one of three Ewing's sarcomas, in a tumor cell subpopulation of two of ten malignant schwannomas, and in the Schwann cell compartment of one of two ganglioneuromas tested. Furthermore, CD30 was consistently expressed in the myoepithelial compartment of 13 fibroadenomas. However, all five lipomas, all seven liposarcomas, all three neuroblastomas, both ganglioneuroblastomas, both chondrosarcomas, and tumors of disputed origin tested were consistently CD30 negative. These findings indicate that, outside the lymphatic system, CD30 antigen is not restricted to epithelial neoplasms but may also be present in tumors of mesenchymal origin. The authors conclude that CD30 antigen, although having limited utility in the differential diagnosis of tumors of questionable histogenesis, may eventually define relevant subgroups within the main tumor categories. .A Mechtersheimer G; Moller P. .I 274584 .U 91003886 .S Cancer 9101; 66(8):1738-42 .M Adult; Aged; Antibodies, Monoclonal/DU; Antigens, Neoplasm/AN/*BI; B-Lymphocytes/*IM/ME; Female; Human; Immunophenotyping/*; Leukemia, B-Cell, Chronic/*IM/ME/PA; Male; Middle Age; Tumor Markers, Biological/AN. .T Immunophenotypes in "classical" B-cell chronic lymphocytic leukemia. Correlation with normal cellular counterpart and clinical findings. .P JOURNAL ARTICLE. .W This study evaluates the expression of a series of membrane antigens, normally expressed by B-lymphocytes of the lymphocytic mantle and marginal zone, in 90 selected cases of "classical" (mouse red blood cell-receptor+, CD20+, CD5+, surface immunoglobulin +/-) B-chronic lymphocytic leukemia (B-CLL) with the aim of contributing toward identifying the normal counterpart of B-CLL and any correlations between surface antigen pattern and certain clinical characteristics. Clustered (CD23, 25, 39, 40, 27, 1c, w75) and unclustered (NuB1, 7F7, KiB3) monoclonal antibodies (MoAb) were tested. Almost all cases showed high reactivity to CD23, 27, w75, 39, 40, and NuB1: expression of CD1c was very low and that of 7F7, KiB3, and CD25 was variable. The reactivity of 7F7 and KiB3 was strictly correlated, and they correlated individually with CD25. Results show that the most frequent B-CLL phenotype (CD19+, 5+, 23+, 27+, 39+, NuB1+, KiB3 +/-, 7F7 +/-, and CD25 +/-) corresponds to one or more cellular subsets in the mantle zone. No correlation was found between MoAb expression, surface immunoglobulin (SIg) class or type, clinical stage, disease activity, or age at diagnosis. The only difference (statistically borderline) was the expression of 7F7 and KiB3 (in young versus old patients). This suggests that modulations in the expression of surface antigens do not affect the clinical behavior of the disease. .A Baldini L; Cro L; Cortelezzi A; Calori R; Nobili L; Maiolo AT; Polli EE. .I 274585 .U 91003887 .S Cancer 9101; 66(8):1743-7 .M Chromosomes, Human, Pair 18/*; Female; Gene Rearrangement/*; Gene Rearrangement, T-Lymphocyte/*; Genes, Immunoglobulin/*; Hong Kong/EP; Human; Immunoglobulin Joining Region/GE; Immunophenotyping; Lymphoma/EP/*GE/IM; Male; Middle Age. .T Rearrangement of immunoglobulin, T-cell receptor, and bcl-2 genes in malignant lymphomas in Hong Kong. .P JOURNAL ARTICLE. .W The pattern of malignant lymphomas in the Hong Kong Chinese population is characterized by a low incidence of Hodgkin's disease and follicular lymphomas. The authors studied the immunoglobulin (Ig), T-cell receptor (TCR), and bcl-2 gene rearrangement in 62 cases of malignant lymphoma in this population by Southern blot hybridization. Two cases of Hodgkin's disease showed no rearrangement of the Ig and TCR genes. All 42 cases of B-cell lymphoma had Ig heavy chain (JH) rearrangement with or without additional rearrangement of the light chains (C kappa and C lambda). One case of diffuse B-cell lymphoma had additional T-cell receptor beta-chain (C beta) rearrangement. Sixteen of 18 cases of T-cell lymphoma had C beta rearrangement, and one case of T-lymphoblastic lymphoma had additional JH rearrangement. Two of eight (25%) cases of follicular lymphoma but only one of the 34 (2.9%) cases of diffuse B-cell lymphoma had bcl-2 rearrangement that was detected by pFL-1 probe. None of the 62 cases showed bcl-2 rearrangement using the pFL-2 probe. In conclusion, the Ig and TCR gene rearrangement pattern of the lymphomas found in Hong Kong correlates well with the T-cell and B-cell lineage, which is similar to reports in the white population. However, the incidence of bcl-2 gene rearrangement in follicular B-cell lymphoma is lower than that reported in the US but comparable with that in Japan. .A Liang R; Chan V; Chan TK; Chiu E; Todd D. .I 274586 .U 91003888 .S Cancer 9101; 66(8):1748-54 .M Adolescence; Cerebrospinal Fluid/*CY; Child; Child, Preschool; Female; Human; Infant; Leukemia, Lymphocytic, Acute, L1/DI/*PA; Leukocyte Count; Leukocytes/*PA; Male; Prognosis; Recurrence. .T Significance of blasts in low-cell-count cerebrospinal fluid specimens from children with acute lymphoblastic leukemia. .P JOURNAL ARTICLE. .W The purpose of this study was to determine whether the presence of more than 5% blasts in a differential count of cytocentrifuged cerebrospinal fluid (CSF) with less than 6 leukocytes/microliter was predictive of central nervous system (CNS) relapse in children with acute lymphoblastic leukemia (ALL). A double concentrate method of cytocentrifuge preparation was used to analyze 4543 consecutive CSF specimens from 349 children with ALL between January 1, 1982, and September 30, 1988. One hundred nine CSF specimens from 58 evaluable children had less than 6 leukocytes/microliter and more than 5% blasts on cytocentrifuge differential count (low-cell-count specimen with blasts [LCB]). During the study period, 25 of 332 evaluable children (7.5%) had CNS leukemic recurrence. In 22 of 25 (88%), the CNS relapse was preceded by at least one abnormal low-cell-count CSF specimen. One of 34 patients with a single LCB at diagnosis (3%) had subsequent CNS relapse compared with five of eight patients (62.5%) with a single LCB during remission (P = 0.0002). Of 16 children with two or more LCB during remission, nine (56%) had CNS relapse defined by standard criteria, whereas six additional patients in this group were declared to be in CNS relapse on the basis of their repetitive LCB. Whether diagnosing CNS recurrence earlier in its course based on a modification of the definition of CNS leukemia will change the frequency of subsequent adverse events or make possible decreased intensity of CNS retreatment remains to be determined. .A Odom LF; Wilson H; Cullen J; Bank J; Blake M; Jamieson B. .I 274587 .U 91003889 .S Cancer 9101; 66(8):1755-8 .M Adult; Child; Enzyme Tests/*; Human; Immunophenotyping; Leukemia, Lymphocytic, Acute/BL/*DI/PA; Prognosis; Prospective Studies; Remission Induction; Support, Non-U.S. Gov't; Tumor Markers, Biological/BL; 5'-Nucleotidase/BL/*ME. .T Prognostic implication of ecto-5'-nucleotidase activity in acute lymphoblastic leukemia. .P CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY. .W Ecto-5'-nucleotidase (5'-N) activity was determined in 191 patients (71 children and 120 adults) with acute leukemia. Elevated values for 5'-N were registered in common acute lymphoblastic leukemia (ALL), but blast cells of T-cell ALL (T-ALL) and common ALL antigen-negative non-T-ALL had low enzyme activity comparable with the values of acute non-lymphocytic leukemia. Dependence of remission duration on 5'-N activity was analyzed in 74 adults with ALL, treated similarly in a prospective multicenter trial. The remission curves for ALL patients with 5'-N activity lower than 10 nmol/h x 10(6) cells were substantially and significantly better than those of patients with high activity (greater than 10 nmol/h x 10(6) cells). This difference was also evident in the immunologic subclass common ALL. Statistical evaluation showed that an interaction between immunologic subtype of the blast cells and their 5'-N activity had prognostic significance for remission duration. In addition to the independent factor, initial age, this interaction was also prognostic for survival. .A Gutensohn W; Thiel E. .I 274588 .U 91003890 .S Cancer 9101; 66(8):1759-62 .M Age Factors; Aged; Human; Middle Age; Receptors, Androgen/*AN; Receptors, Estrogen/*AN; Receptors, Progesterone/*AN; Thyroid Diseases/PA; Thyroid Gland/*CH/PA; Thyroid Neoplasms/*CH/PA. .T Sex hormone receptors in human thyroid tissues. .P JOURNAL ARTICLE. .W The behavior of sex hormone receptors was studied in the cytosol of thyroid tissue samples in order to clarify the effects of sex hormones on diseases of the thyroid. Androgen receptor (AR), estrogen receptor (ER), and progesterone receptor (PgR) were assayed using the dextran-coated charcoal (DCC) method and analyzed by the method of Scatchard. Androgen receptor, ER, and PgR were negative in all of the cytosol prepared from normal thyroid tissues. However, the positive rates for the receptors in the neoplastic and nonneoplastic tissues were 22% for AR, 29% for ER, and 18% for PgR. Especially, the incidence of ER was significantly higher in neoplastic lesions than normal tissues. These data suggest that sex hormones, especially estrogen, may play a role in diseases of the thyroid. .A Miki H; Oshimo K; Inoue H; Morimoto T; Monden Y. .I 274589 .U 91003891 .S Cancer 9101; 66(8):1763-8 .M Blotting, Southern; Carcinoma, Oat Cell/CH/*CO/PA; Case Report; DNA, Viral/AN; Human; HTLV-I/GE; HTLV-I Infections/*CO/PA; Lung Neoplasms/CH/*CO/PA; Male; Middle Age; Receptors, Interleukin-2/AN; Support, Non-U.S. Gov't; Tumor Markers, Biological/AN. .T Human T-cell leukemia virus type 1 associated with small cell lung cancer. .P JOURNAL ARTICLE. .W A patient with small cell lung cancer (SCLC) whose serum contained high levels of soluble interleukin-2 receptors is reported. Soluble interleukin-2 receptors in the supernatant of cultured SCLC cells obtained from the patient's pleural effusion while he had malignant pleuritis, increased almost linearly from the time of cell seeding. The expression of interleukin-2 receptors (Tac) on the SCLC cells were demonstrated by an immunofluorescence study. However, other lymphocytic markers, including OKT 11, OKT 4, OKT 8, B 1, and B 4, were not found on the cells with the exception of the natural killer cell marker, NKH-1. Southern blot analysis indicated the rearrangement of the T-cell receptor of the cancer cells. Moreover, monoclonal integration of human T-cell leukemia virus type 1 (HTLV-1) provirus in DNA from the cancer cells was also demonstrated. These observations suggest that some SCLC in HTLV 1 endemic areas are associated with HTLV-1. .A Matsuzaki H; Asou N; Kawaguchi Y; Hata H; Yoshinaga T; Kinuwaki E; Ishii T; Yamaguchi K; Takatsuki K. .I 274590 .U 91003892 .S Cancer 9101; 66(8):1769-74 .M Human; Lewis Blood-Group System/*IM; Phenotype; Precancerous Conditions/*BL/PA; Stomach Neoplasms/*BL/PA; Support, Non-U.S. Gov't. .T Lewis system alterations in gastric carcinogenesis. .P JOURNAL ARTICLE. .W Alterations in the expression of type 1 blood group-related antigens (Lewis a and b) were examined immunohistochemically in 371 consecutives gastric biopsy and 80 surgical specimens from patients of gastric carcinoma. The ABH and Lewis phenotype and secretor status of the patients were correlated with histologic findings. An anomalous expression of Lewis a antigen was found in 88 of 249 gastric biopsy specimens of Lewis (a-b+) phenotype patients. The prevalence of this anomaly increased with the evolution of the premalignant process, in agreement with the commonly accepted model of gastric carcinogenesis. Thus, anomalous Lewis a antigen appeared in 66.6% of gastric dysplasia cases, in 64.6% of intestinal metaplasia, in 15.4% of atrophic gastritis, and in 7.4% of superficial gastritis. No alterations were found in subjects with normal gastric mucosa. Forty-seven of the 49 Lewis (a-b+) phenotype gastric carcinoma patients showed antigenic alterations in tumor cells (anomalous Lewis a antigen in 36 and loss of Lewis antigens in 11). In 26 of these gastric specimens an anomalous Lewis a antigen was present in areas of intestinal metaplasia and/or dysplasia away from the area of neoplastic transformation. The expression of Lewis a antigen in Lewis (a-b+) phenotype patients is a frequent phenomenon in gastric neoplastic cells and could result from the blocked synthesis of Lewis b antigen with accumulation of its precursors. These findings suggest that, during gastric carcinogenesis, antigenic alterations may precede neoplastic transformation. An anomalous Lewis a antigen could constitute a significant index of severity of the histologic lesion and contribute to identifying high-risk individuals. .A Torrado J; Blasco E; Gutierrez-Hoyos A; Cosme A; Lojendio M; Arenas JI. .I 274591 .U 91003893 .S Cancer 9101; 66(8):1775-80 .M Adenocarcinoma/CH/*GE/PA; Comparative Study; DNA, Neoplasm/*AN; Female; Human; Lymphatic Metastasis; Male; Middle Age; Stomach Neoplasms/CH/*GE/PA; Support, Non-U.S. Gov't. .T Comparison of DNA content in gastric cancer cells between primary lesions and lymph node metastases. .P JOURNAL ARTICLE. .W Cytophotomtric DNA contents of tumor cells in primary lesions and the corresponding metastatic lymph nodes were compared in 61 cases of gastric cancer to determine whether the DNA content remains stable during lymph node metastasis. The DNA distribution patterns were grouped into three types, according to the proportion of aneuploid cell population. Changes in DNA patterns between primary and metastatic lesions were evident in 36 of 61 patients (59.0%); in the remaining 25 (41.0%), the same DNA distribution patterns were noted for both lesions. In 33 of these 36, DNA pattern in the primary carcinoma was transformed into a more narrowly scattered one in the metastatic lesion of the lymph node. Mean and modal values and the frequency of cells over tetraploid (4c) or hexaploid (6c) were significantly higher in the primary lesion compared with findings in the metastatic lesions. This reduction in DNA content in the metastatic lesions was a more frequent occurrence in differentiated (18 of 23) than in undifferentiated adenocarcinoma (15 of 35) (P less than 0.01). Therefore, in primary lesions with a widely scattered DNA ploidy, the tumor cells with a smaller DNA ploidy frequently metastasized to lymph nodes, particularly in cases of a differentiated carcinoma. Such observations may be pertinent in future designing of treatment protocols. .A Baba H; Korenaga D; Okamura T; Sugimachi K. .I 274592 .U 91003894 .S Cancer 9101; 66(8):1781-8 .M Aged; Antineoplastic Agents, Combined/*TU; Bleomycins/AD; Case Report; Cyclophosphamide/AD; Doxorubicin/AD; Etoposide/AD; Female; Human; Immunohistochemistry; Leucovorin/AD; Lymphoma, Large-Cell/DI/DT/*PA; Male; Methotrexate/AD; Middle Age; Prednisone/AD; Procarbazine/AD; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Vincristine/AD. .T Angiotropic (intravascular) large cell lymphoma. A clinicopathologic study of seven cases with unique clinical presentations. .P JOURNAL ARTICLE. .W The authors recently reported the antigenic phenotypes of three cases of so-called "malignant angioendotheliomatosis" and suggested that angiotropic large cell lymphoma (ALCL) is a more appropriate designation for this disease. The authors now report an additional seven cases of ALCL with unique clinical presentations. One patient presented with prostate enlargement, the second with lytic bone lesions and thickened nasal sinus mucosa, the third had diffuse myalgia, the fourth had dyspnea and pulmonary infiltrates, the fifth had gangrene of the lower extremities, total-body skin involvement, and pancytopenia, the sixth had a lesion of the foreskin mimicking squamous cell carcinoma, and the seventh had a mediastinal mass. In all cases histologic features were characteristic of ALCL with, in two cases, extravascular spread into soft tissue. Immunohistologic studies showed a B-cell phenotype in five cases and a T-cell phenotype in one case. Two patients received combination chemotherapy using established treatment protocol for large cell lymphoma, and remain in complete clinical remission and two patients are responding clinically to combination chemotherapy. Two patients died shortly after receiving combination chemotherapy. One patient has only recently been diagnosed as having ALCL and no long-term follow-up is available. These data indicate that, although ALCL affects predominantly the central nervous system and skin, unusual clinical presentations may occur, and patients with ALCL may respond to combination chemotherapy for large cell lymphoma. .A Stroup RM; Sheibani K; Moncada A; Purdy LJ; Battifora H. .I 274593 .U 91003895 .S Cancer 9101; 66(8):1789-95 .M Actuarial Analysis; Adult; Aged; Carcinoma/*GE/MO/PA/RT; Carcinoma, Squamous Cell/*GE/MO/PA/RT; DNA, Neoplasm/*AN; Female; Flow Cytometry; Human; Male; Middle Age; Nasopharyngeal Neoplasms/*GE/MO/PA/RT; Prognosis; Retrospective Studies; Support, Non-U.S. Gov't; Survival Analysis. .T A clinical and flow cytometric analysis of patients with nasopharyngeal cancer. .P JOURNAL ARTICLE. .W Abnormal cellular DNA content, a hallmark of malignancy, is known to be an important prognostic factor in many human solid tumors; however, no data have been published on whether cellular DNA content carries prognostic significance for patients with nasopharyngeal cancer (NPC). Archival, formalin-fixed, paraffin-embedded pathology specimens representing pretreatment tissue biopsies from 55 patients (41 men and 14 women) with NPC were analyzed for cellular DNA content in a retrospective fashion from 1968 to 1988. Individual tumors were classified as either lymphoepithelioma, squamous cell, or anaplastic carcinoma, and were staged according to International Union Against Cancer (UICC) criteria. All patients were treated with curative intent using a 4 to 6 MeV linear accelerator to total doses ranging from 50 to 60 Gy in 4 to 6 weeks. The overall 5-year actuarial survival for all 55 patients was 44.4% (men, 41%; women, 52%). Survival by T stage was as follows: T1, 65%; T2, 51%; T3, 36%; and T4, 27%. Similarly, the 5-year survival rate declined as the bulk of nodal metastases increased: N0, 62%; N2, 50%; N3, 37%; and N1, 25%. Patients who had anaplastic carcinoma had a 5-year survival of 73%, those with lymphoepithelioma had a 60% survival, and those with squamous cell cancer (SCC) had a 30% survival. There was a statistically significant difference in 5-year survival between patients with SCC and those with nonkeratinizing histologies (P less than 0.05). In addition, there was a significant association between patients older than 40 years of age with SCC and patients younger than 40 years of age with nonkeratinizing malignancies (P less than 0.01). Of the 55 tumors successfully analyzed, 22 (40%) were diploid and 33 (60%) were aneuploid. The mean coefficient of variation (CV) of all 55 samples was 6.17%. There was no significant difference in 5-year survival between patients with diploid and those with aneuploid tumors (48% versus 42%). Furthermore, there was no statistically significant survival difference between aneuploid and diploid tumors within any one histologic subgroup. There was also no significant survival difference related to the DNA index. The results indicate that the extent of local tumor spread is still the most important prognostic factor for patients treated with radiotherapy for NPC. The data support the conclusion that patients with lymphoepithelioma and anaplastic carcinomas have a superior survival to patients with squamous cell carcinoma.(ABSTRACT TRUNCATED AT 400 WORDS) .A Costello F; Mason BR; Collins RJ; Kearsley JH. .I 274594 .U 91003896 .S Cancer 9101; 66(8):1796-801 .M Aged; Carcinoma, Mucinous/*PA/UL; Case Report; Female; Human; Microscopy, Electron; Submandibular Gland Neoplasms/*PA/UL. .T Mucinous adenocarcinoma of the submandibular gland. .P JOURNAL ARTICLE. .W A rare tumor not easily classifiable among published histologic categories for salivary gland tumors is reported. The neoplasm developed within the submandibular gland of a 78-year-old woman with invasion of the mandible and metastasis to regional lymph nodes. Histopathologically, cuboidal cells possessing clear cytoplasm and displaced round nuclei proliferated and exhibited an adenomatous pattern. Many cystic spaces surrounded by tumor cell strands were seen, mucus substance filled in the cystic spaces, and the tumor cells seemed mucus-secreting, but neither epidermoid cells nor papillary appearance could be observed. Electromicroscopically, numerous mucous droplets of low electron density were prominent in the cytoplasm, and the tumor cells had sparse irregular microvilli on the luminal surface. Mucin histochemistry, including paradoxical concanavalin A staining, revealed that the tumor cells contained neutral and acid mucins, and these were identified as class II and III mucosubstances. No other neoplastic lesion, except recurrent metastatic neck nodes, has been detected 6 years after the first examination, and it seems that the tumor is a rare primary mucinous adenocarcinoma of the submandibular gland. .A Osaki T; Hirota J; Ohno A; Tatemoto Y. .I 274595 .U 91003898 .S Cancer 9101; 66(8):1810-6 .M Antineoplastic Agents, Combined/TU; Breast Neoplasms/CH/*GE/PA/TH; Combined Modality Therapy; Drug Therapy, Combination; DNA, Neoplasm/*AN; Female; Flow Cytometry; Human; Lymphatic Metastasis; Mastectomy, Modified Radical; Menopause; Ploidies/*; Prognosis; Receptors, Estrogen/*AN; Receptors, Progesterone/*AN; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tamoxifen/TU. .T The use of flow cytometry for the prognosis of stage II adjuvant treated breast cancer patients. .P JOURNAL ARTICLE. .W Characterization of breast cancer cells by histology, flow cytometry, and steroid receptors was performed on 197 Stage II breast node positive cancer patients given adjuvant chemotherapy, plus tamoxifen for patients with positive hormone receptors. Histologic and steroid receptor assays were performed using standard techniques; flow cytometric analysis was performed from paraffin-embedded blocks obtained from the primary tumor. Quality control studies on reproducibility, tissue heterogeneity, and analysis procedures have been included. Of the 197 patients studied, aneuploidy was found in 102 (52%); the median %S value was 8% with a range of 0.4% to 38%. Our results demonstrated that number of positive nodes, receptor status, and grade were of prognostic value. Cell cycle kinetic data were not of independent prognostic value in this series. However, ploidy could differentiate in prognosis in the receptor-negative subgroup. Patients with receptor-negative tumors had a significantly better overall survival if the tumor was diploid in nature. Cell kinetics was not significantly prognostic for either receptor subgroup, although patients with higher %S tended to have better relapse-free and overall survival. This is in disagreement with other studies and may demonstrate that treatment has confounded our results and diminished the ability of flow cytometry data to help predict outcome. .A Kute TE; Muss HB; Cooper MR; Case LD; Buss D; Stanley V; Gregory B; Galleshaw J; Booher K. .I 274596 .U 91003899 .S Cancer 9101; 66(8):1817-27 .M Adenocarcinoma/*DI/PA; Antibodies, Monoclonal/*DU/IM; Biopsy, Needle; Carcinoma/*DI/PA; Carcinoma, Squamous Cell/*DI/PA; Comparative Study; Diagnosis, Differential; Female; Fluorescent Antibody Technique; Human; Immunohistochemistry; Intermediate Filaments/IM; Lung Neoplasms/*DI/PA; Male; Smoking/PA; Support, Non-U.S. Gov't. .T Immunocytochemical characterization of lung tumors in fine-needle aspiration. The use of cytokeratin monoclonal antibodies for the differential diagnosis of squamous cell carcinoma and adenocarcinoma. .P JOURNAL ARTICLE. .W In the current study, immunocytochemical typing of intermediate filaments was used for a differential diagnosis of human lung tumors from transthoracic fine-needle aspiration biopsies (TFNAB). The authors have compared the cytologic diagnosis of 53 lung cancer cases with the immunofluorescence patterns obtained using a panel of monoclonal antibodies, five of which (KG 8.13, KM 4.62, Ks B.17, KS 8.12, KK 8.60) react with specific cytokeratin polypeptides and one with vimentin (VIM 13.2). Only in six of 23 samples cytologically diagnosed as squamous cell carcinoma did the immunocytochemical typing of cytokeratins (ICTC) confirm the cytologic diagnosis. In seven cases some of the tumor cells stained positively with antibody Ks B.17 specific for simple epithelial keratin (No: 18), suggesting the presence of some cells of glandular origin. In ten additional cases the ICTC was in conflict with the cytologic diagnosis of squamous cell carcinoma (i.e., antibodies Ks 8.12 and KK 8.60 were negative, and antibody Ks B.17, positive) supporting a diagnosis of adenocarcinoma. In 14 of 18 cases cytologically diagnosed as adenocarcinoma, the ICTC confirmed the diagnosis whereas in four cases additional presence of some squamous cells was noticed. The ICTC labeling of cases cytologically diagnosed as undifferentiated and large cell carcinomas was similar to that of the group of adenocarcinomas. Thus, the application of cytokeratin typing for TFNAB samples seems to provide a vital complementation to routine cytologic study, especially for cases cytologically diagnosed as squamous carcinoma. .A Bruderman I; Cohen R; Leitner O; Ronah R; Guber A; Griffel B; Geiger B. .I 274597 .U 91003900 .S Cancer 9101; 66(8):1828-32 .M Adenocarcinoma/MO/*PA; Comparative Study; Human; Japan; Lymphatic Metastasis; Neoplasm Staging/*MT; Stomach Neoplasms/MO/*PA; Support, Non-U.S. Gov't; United States. .T Comparison of the conventional method of lymph node staging with a comprehensive fat-clearing method for gastric adenocarcinoma. .P JOURNAL ARTICLE. .W Discrepant results in long-term survival between United States and Japanese patients with resectable gastric adenocarcinoma may result from more accurate staging in the Japanese series. The authors compared a comprehensive fat-clearing method with the conventional pathology method of lymph node sampling in 11 patients undergoing curative gastrectomy and extended lymphadenectomy at their institution. Comprehensive fat-clearing doubled total lymph node counts (P less than 0.01), identified smaller lymph nodes (P less than 0.001), and identified more histologically involved nodes of significantly smaller size (P less than 0.001). Comprehensive fat-clearing pathologically upstaged 29% of the authors' eligible specimens. Accurate pathologic staging is necessary when comparing Japanese and United States survival data for resectable gastric adenocarcinomas. .A Candela FC; Urmacher C; Brennan MF. .I 274598 .U 91003901 .S Cancer 9101; 66(8):1833-5 .M Adrenal Gland Neoplasms/*BL/DI; Adult; Aged; Diagnosis, Differential; Female; Human; Male; Middle Age; Neuropeptide Y/*BL; Pheochromocytoma/*BL/DI; Phosphopyruvate Hydratase/*BL; Tumor Markers, Biological/BL. .T Neuropeptide Y and neuron-specific enolase levels in benign and malignant pheochromocytomas. .P JOURNAL ARTICLE. .W Neuron-specific enolase (NSE) is the isoform of enolase, a glycolytic enzyme found in the neuroendocrine system. Neuropeptide Y (NPY) is a peptide recently discovered in the peripheral and central nervous systems. Serum NSE and plasma NPY levels have been reported to be increased in some patients with pheochromocytoma. The authors evaluated whether the measurement of these molecules could help to discriminate between benign and malignant forms of pheochromocytoma. The NSE levels were normal in all patients with benign pheochromocytoma (n = 13) and elevated in one half of those with malignant pheochromocytoma (n = 13). Plasma NPY levels were on the average significantly higher in the malignant (177.1 +/- 38.9 pmol/l, n = 16) than in the benign forms of the disease (15.7 +/- 389 pmol/l, n = 24). However, there was no difference in the percentage of patients with elevated NPY levels. These results show that determination of serum NSE may be useful for distinguishing between malignant and benign pheochromocytoma; the measurement of plasma NPY is not useful for differentiating the two kinds of tumors. .A Grouzmann E; Gicquel C; Plouin PF; Schlumberger M; Comoy E; Bohuon C. .I 274599 .U 91003902 .S Cancer 9101; 66(8):1836-42 .M Aged; Bladder Neck Obstruction/ET; Bladder Neoplasms/CO/*PA/TH/UL; Case Report; Combined Modality Therapy; Histiocytoma/CO/*PA/TH/UL; Human; Male; Microscopy, Electron. .T Myxoid malignant fibrous histiocytoma of the bladder. .P JOURNAL ARTICLE. .W Although the most common soft tissue sarcoma of adulthood, malignant fibrous histiocytoma (MFH) is an extremely rare tumor of the urinary bladder. Only three well-documented cases have been reported in the world literature. The patient presented in this report represents the first case of the myxoid variant to develop in the urinary bladder. Whereas all previous patients with MFH of the bladder had intermittent hematuria, this patient's chief complaint was bladder outlet obstruction due to extension of the tumor into the prostate. He was managed with radical cystoprostatectomy, postoperative radiation therapy to the tumor bed, and adjuvant chemotherapy using doxorubicin. The patient tolerated the therapy well and was disease-free at the 3-year follow-up visit. The histogenesis, clinical features, pathologic characteristics, and treatment considerations of this rare bladder tumor are discussed in detail. .A Oesterling JE; Epstein JI; Brendler CB. .I 274600 .U 91003903 .S Cancer 9101; 66(8):1843-9 .M Adenocarcinoma/GE/PA/SC; Carcinoma/GE/PA/SC; Diagnosis, Differential; DNA, Neoplasm/*AN; Female; Flow Cytometry; Human; Likelihood Functions; Neoplasms, Multiple Primary/DI/*GE/PA; Ovarian Neoplasms/*GE/PA/SC; Ploidies/*; Uterine Neoplasms/*GE/PA/SC. .T Flow cytometric DNA-ploidy analysis of synchronously occurring multiple malignant tumors of the female genital tract. .P JOURNAL ARTICLE. .W In this study the authors applied flow cytometric DNA-ploidy analysis to multiple female genital tract malignant tumors in 43 patients, most of whom (n = 37) had bilateral ovarian cancer. An algorithm was developed for calculation of the likelihood ratio of the probabilities that measured DNA index differences between multiple tumor localizations within the same patient could be attributed to measurement variation or to true biologic DNA content differences. The results of this statistical analysis show that in 72% of the cases (31 of 43) this probability ratio exceeded 1. Because the probability that two independent tumors will have a near-identical aneuploid DNA content is very low, this finding supports a metastatic process rather than the occurrence of multiple primary tumors in these patients. Thus, flow cytometric DNA-ploidy analysis can be helpful in the identification of metastatic disease in patients with multiple female genital tract malignant tumors. .A Smit VT; Fleuren GJ; van Houwelingen JC; Zegveld ST; Kuipers-Dijkshoorn NJ; Cornelisse CJ. .I 274601 .U 91003904 .S Cancer 9101; 66(8):1850-5 .M Adolescence; Adult; Aged; Aged, 80 and over; Child; Female; Hong Kong; Human; Lymphoma, Non-Hodgkin's/*MO/PA; Male; Middle Age; Neoplasm Staging; Support, Non-U.S. Gov't; Survival Analysis. .T Histologic subtypes and survival of Chinese patients with non-Hodgkin's lymphomas. .P JOURNAL ARTICLE. .W The histologic subtypes and survival of 840 Chinese patients with non-Hodgkin's lymphoma (NHL) were reviewed. All cases were classified according to the Rappaport and Kiel systems and the Working Formulation (WF). A low incidence of nodular/follicular lymphomas (12%) was observed. The most common histologic subtypes were diffuse histiocytic, diffuse centroblastic, and diffuse large cell lymphomas, according to Rappaport, Kiel, and the WF, respectively. A high proportion (24%) of the cases were unclassifiable, according to Kiel, because of the precise terms of the classification. The "favorable"-prognosis NHL, according to Rappaport, or the low-grade NHL, according to Kiel and the WF, had a more indolent clinical course. However, except for the nodular mixed (Rappaport) or follicular mixed (WF) lymphomas which appeared to behave like the more aggressive NHL, a plateau was not seen in the survival curves of our patients with other kinds of favorable-prognosis or low-grade NHL, indicating the lack of curative potential of these tumors. The lymphoplasmacytoid lymphoma, according to Kiel, also appeared to have a more aggressive clinical course. A plateau was seen in most of the other survival curves of patients with the more aggressive tumors, indicating the prospect of cure. However, the prognosis of the very aggressive tumors such as the diffuse lymphoblastic and diffuse small noncleaved cell lymphomas, according to the WF, remains very poor with a median survival of less than 10 months. .A Liang R; Loke SL; Ho FC; Chiu E; Chan TK; Todd D. .I 274602 .U 91003905 .S Cancer 9101; 66(8):1856-60 .M Agammaglobulinemia/ET; Antineoplastic Agents, Combined/*TU; Case Report; Child; Cyclophosphamide/AD; Dexamethasone/TU; Doxorubicin/AD; Drug Therapy, Combination; DNA, Viral/AN; Epstein-Barr Virus/GE; Human; Lymphoma, B-Cell/CO/*DI/DT/MI; Male; Meningeal Neoplasms/CO/*DI/DT/MI; Methotrexate/AD; Vincristine/AD. .T Primary leptomeningeal B-cell lymphoma in a 8-year-old child. .P JOURNAL ARTICLE. .W A case of primary leptomeningeal B-cell lymphoma in an 8-year-old, previously healthy child is described. The child was found to have hypogammaglobulinemia, and the Epstein-Barr virus genome was identified in cultured tumor cells despite blood serology being negative for the virus. The patient was treated with cyclophosphamide, doxorubicin, vincristine, and dexamethasone, plus intrathecal methotrexate, and initially improved. Before the initiation of craniospinal radiation, the patient developed progressive disease, deteriorated, and died 9 months after the onset of symptoms. .A Hayani A; Venger BH; Rouah E; Laurent JP; Mahoney DH; McClain KL. .I 274603 .U 91004180 .S Cathet Cardiovasc Diagn 9101; 20(4):227-37 .M Adult; Aged; Aged, 80 and over; Angioplasty, Transluminal, Percutaneous Coronary/*MT; Combined Modality Therapy; Comparative Study; Coronary Disease/*TH; Coronary Vessels/RA; Double-Blind Method; Female; Follow-Up Studies; Human; Male; Methylprednisolone/AD; Middle Age; Myocardial Infarction/*TH; Recurrence; Support, Non-U.S. Gov't. .T Multi-Hospital Eastern Atlantic Restenosis Trial: design, recruitment, and feasibility. M-HEART Investigators. .P CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL. .W A randomized control trial was set up to examine factors that influence restenosis and determine the effects of corticosteroids on restenosis following successful PTCA. The rationale for the study agent chosen, design, recruitment, and feasibility, as well as initial patient demographic data and initial results are presented. .A Hill JA; Macdonald RG; Jugo R; Hirshfeld JW Jr; Goldberg S; Savage MP; Vetrovec G; Cowley M; Bass TA; Margolis JR; et al. .I 274604 .U 91004181 .S Cathet Cardiovasc Diagn 9101; 20(4):238-40 .M Adult; Angioplasty, Transluminal, Percutaneous Coronary/*IS; Case Report; Combined Modality Therapy; Coronary Artery Bypass; Coronary Disease/*TH; Coronary Vessels/*RA; Equipment Failure; Follow-Up Studies; Foreign Bodies/*RA; Human; Male; Postoperative Complications/TH; Recurrence; Reoperation. .T Fractured and retained guide-wire fragment during coronary angioplasty--unforeseen late sequelae. .P JOURNAL ARTICLE. .W During a difficult coronary angioplasty, the tip of the guide wire became inadvertently wedged in a distal vessel, fractured, and retained in situ. Because of the otherwise successful nature of the angioplasty and the patient's great risk for cardiac surgery, it was elected to leave the wire fragment in place. Recurrence of symptoms led to recatheterization, which in addition to restenosis of the original angioplasty site showed diffuse narrowing of the arterial segment that contained the retained wire fragment. This occurred despite systemic anticoagulation with Coumadin in the interval between procedures. Thus retained guide wire fragments in patent coronary arteries may cause arterial narrowing despite systemic anticoagulation. .A Doorey AJ; Stillabower M. .I 274605 .U 91004182 .S Cathet Cardiovasc Diagn 9101; 20(4):241-3 .M Adult; Angina, Unstable/RA; Case Report; Chest Pain/RA; Coronary Vessel Anomalies/GE/*RA; Coronary Vessels/*RA; Diagnosis, Differential; Human; Karyotyping; Klinefelter's Syndrome/GE/*RA; Male; Periostitis/RA. .T Klinefelter's syndrome with anomalous origin of left main coronary artery [see comments] .P JOURNAL ARTICLE. .W Klinefelter's syndrome is a rare entity. Even rarer is an anomalous origin of the Left Main Coronary Artery. For both conditions to occur in the same patient is hence exceedingly rare. Reported here is a never previously reported case of a coronary congenital anomaly in a patient with Klinefelter's syndrome together with the proper angiographic approach. .A Albazzaz SJ. .I 274606 .U 91004183 .S Cathet Cardiovasc Diagn 9101; 20(4):244-6 .M Adult; Angioplasty, Transluminal, Percutaneous Coronary/*IS; Aortography; Case Report; Coronary Disease/*TH; Equipment Failure; Femoral Artery/*RA; Heart Catheterization/*IS; Human; Iliac Artery/*RA; Male; Recurrence. .T Entrapment of a folded-over introducer sheath in the iliofemoral artery: an unusual complication of PTCA guiding catheter exchange [see comments] .P JOURNAL ARTICLE. .W An arterial introducer sheath became folded over in the iliac artery during PTCA. This probably resulted from withdrawal of a doubled over Judkins left coronary guiding catheter through the introducer sheath. Nonsurgical, atraumatic removal was accomplished after the acute bend of the introducer sheath had been withdrawn to the site of arterial entrance. .A Marsa RJ; Smith DC; Park JS; Jang GD. .I 274607 .U 91004184 .S Cathet Cardiovasc Diagn 9101; 20(4):247-50 .M Angioplasty, Transluminal, Percutaneous Coronary/*IS; Case Report; Coronary Vessels/*/RA; Emergencies/*; Equipment Failure; Foreign Bodies/*TH; Human; Male; Middle Age; Myocardial Infarction/RA/*TH. .T An alternative method for transcatheter retrieval of intracoronary angioplasty equipment fragments. .P JOURNAL ARTICLE. .A Mintz GS; Bemis CE; Unwala AA; Hadjimiltiades S; Kimbiris D. .I 274608 .U 91004185 .S Cathet Cardiovasc Diagn 9101; 20(4):251-3 .M Angiography; Angioplasty, Transluminal/*MT; Arterial Occlusive Diseases/RA/*TH; Case Report; Human; Intermittent Claudication/TH; Ischemia/RA/*TH; Leg/*BS; Male; Middle Age; Support, Non-U.S. Gov't. .T Retrograde recanalization of an occluded posterior tibial artery by using a posterior tibial cutdown: two case reports. .P JOURNAL ARTICLE. .W Recanalization of two occluded posterior tibial arteries was successfully achieved by utilizing a retrograde approach via a posterior tibial artery cutdown at the level of the ankle. Both cases were previously unsuccessfully attempted by using an antegrade approach. Thus, the choice of access vessel (arterial entry site) becomes a crucial determinant of angioplasty success. .A Iyer SS; Dorros G; Zaitoun R; Lewin RF. .I 274609 .U 91004186 .S Cathet Cardiovasc Diagn 9101; 20(4):254-6 .M Angioplasty, Transluminal/*IS; Atherosclerosis/RA/*TH; Case Report; Combined Modality Therapy; Endarterectomy/*IS; Human; Hypertension, Renovascular/TH; Male; Middle Age; Recurrence; Renal Artery/RA; Renal Artery Obstruction/RA/*TH. .T Percutaneous high-speed rotational atherectomy (Rotablator) of a restenosed ostial renal artery: a case report. .P JOURNAL ARTICLE. .A Zaitoun R; Dorros G; Iyer SS; Lewin RF. .I 274610 .U 91004187 .S Cathet Cardiovasc Diagn 9101; 20(4):257-60 .M Angina Pectoris/TH; Angioplasty, Transluminal, Percutaneous Coronary/*IS; Case Report; Coronary Disease/RA/*TH; Coronary Vessels/RA; Heart Catheterization/*IS; Human; Male; Middle Age. .T Use of the Arani Guiding Catheter with a twist. .P JOURNAL ARTICLE. .A Rizzo TF; Silverstein DK. .I 274611 .U 91004188 .S Cathet Cardiovasc Diagn 9101; 20(4):261-6 .M Angiography/*IS; Angioplasty, Transluminal, Percutaneous Coronary/*IS; Coronary Disease/RA/*TH; Coronary Vessels/RA; Heart Catheterization/*IS; Human. .T Angioplasty of small-diameter coronary arteries using an angiographic catheter and probe. .P JOURNAL ARTICLE. .A Webb JG; Myler RK; Stertzer SH; Guermonprez JL; Jais JM; Maouad J. .I 274612 .U 91004189 .S Cathet Cardiovasc Diagn 9101; 20(4):267-70 .M Animal; Blood Coagulation/*DE; Embolization, Therapeutic/*IS; Heparin/*AD; Polyethylene Terephthalate/*; Steel/*; Vascular Patency/DE; Whole Blood Coagulation Time. .T Systemic heparinization does not prevent clot formation in coil embolization. .P JOURNAL ARTICLE. .W Therapeutic transcatheter closure with Gianturco-type steel coils has been applied to a variety of vascular communications in children with congenital heart disease. Vessel closure depends upon successful thrombus formation around the coil. Since systemic anticoagulation with heparin is commonly used during catheterization and cardiac surgery, we studied the effect of systemic heparinization on the efficiency of vessel occlusion by coil embolization in lambs. Catheters inserted in femoral arteries were used to arteriographically locate and size 36 systemic arteries in 9 lambs weighing 4.2 to 7.4 kg. Twenty-four vessels were embolized prior to heparinization with 400 u/kg heparin, IV. Effective anticoagulation was demonstrated by post-heparin activated clotting time (ACT) values greater than 300 sec. Seven vessels (29%) were not successfully coil-embolized because of inadequate coil position or distant embolization of the coil; 17 (71%) of these vessels were shown to be successfully occluded by arteriography 6 to 77 min later. After a period of systemic heparinization ranging from 71 to 159 min, 9/17 arteries remained occluded, 7/17 could not be examined arteriographically due to early demise of the animal, and only 1/17 showed recanalization. A second group of 12 vessels were embolized after heparinization. Eight (75%) were successfully occluded, and 4 (25%) were not successfully coil-embolized because of inadequate coil position or coil embolization to distant arteries. We conclude that systemic heparinization had no measurable effect on occlusion rates in coil-embolized systemic arteries in the lamb. These data support the use of systemic heparinization, when indicated, during or following therapeutic coil embolization in children. .A Johnson WH Jr; Peterson RK; Howland DF; Lock JE. .I 274613 .U 91004190 .S Cathet Cardiovasc Diagn 9101; 20(4):271-5 .M Aortic Valve/*PP; Aortic Valve Stenosis/DI/*PP; Blood Pressure/*PH; Heart Catheterization/*; Human; Support, U.S. Gov't, Non-P.H.S.. .T Simplified method for estimating true aortic valve mean gradient from simultaneous left ventricular and peripheral arterial pressure recordings. .P JOURNAL ARTICLE. .W Estimation of the aortic valve gradient by simultaneous recording of left ventricular and peripheral arterial pressures is subject to error due to delay and modulation of the arterial pressure contour as it propagates from the ascending aorta. This error can be corrected by averaging the mean gradients derived from unaltered and temporally aligned simultaneous left ventricular-peripheral arterial pressure tracings. In 26 patients with aortic stenosis and simultaneous recordings of ascending aortic and femoral arterial pressure we compared this method with a simplified approach in which the peripheral arterial pressure is partially aligned by advancing it against the left ventricular pressure by 50% of the time delay of the simultaneously recorded upstrokes. Gradients measured this way predicted the true aortic valve gradients (left ventricular-ascending aortic) with a mean difference of +1.1 mm Hg (range = +10 to -5 mm Hg). We recommend use of this simplified method of correction because it predicts true aortic valve gradient equally well as the averaging technique (r = 0.977 vs. 0.979) and requires half the time and effort. .A Folland ED; Parisi AF; Comei C. .I 274614 .U 91004191 .S Cathet Cardiovasc Diagn 9101; 20(4):276-8 .M Adult; Aged; Aged, 80 and over; Angioplasty, Transluminal, Percutaneous Coronary/*IS; Coronary Disease/*TH; Heart Catheterization/*IS; Human; Middle Age; Myocardial Reperfusion/*IS. .T Experience with the use of coronary autoperfusion catheter during complicated angioplasty. .P JOURNAL ARTICLE. .W Between February and July of 1989, 22 patients underwent the use of the Stack autoperfusion catheter following acute occlusion or obstructive dissection during coronary angioplasty; in 20 cases conventional balloon was used in an attempt to correct the angiographic appearance followed by the use of Stack catheter when results were sub-optimal. Only 1 patient (4.5%) required surgical revascularization. Although our study is not prospective or randomized, our observations suggest a significant impact in decreasing the need for emergency surgical revascularization after complicated coronary angioplasty with the use of this approach. .A Saenz CB; Schwartz KM; Slysh SJ; Palanca K; Curry RC Jr. .I 274615 .U 91004192 .S Cathet Cardiovasc Diagn 9101; 20(4):287 .M Comparative Study; Contrast Media/*; Coronary Vessels/*RA; Diatrizoate/*AE; Diatrizoate Meglumine/*AE; Drug Combinations; Human; Iopamidol/*AE; Risk Factors; Ventricular Fibrillation/*CI. .T Ventricular fibrillation during coronary arteriography [letter; comment] .P COMMENT; LETTER. .A Hirshfeld JW Jr. .I 274616 .U 91004193 .S Cathet Cardiovasc Diagn 9101; 21(1):1-6 .M Angioplasty, Transluminal, Percutaneous Coronary/*AE; Comparative Study; Coronary Arteriosclerosis/*ET/RA; Coronary Vessels/IN/RA; Female; Follow-Up Studies; Human; Male; Middle Age; Prospective Studies; Recurrence; Time Factors. .T Does percutaneous transluminal coronary angioplasty accelerate atherosclerotic lesions? .P JOURNAL ARTICLE. .W Recent reports have suggested that angioplasty may cause or accelerate coronary arterial stenoses secondary to traumatic injury. Ninety-four coronary angiograms performed in a 1 yr period were reviewed in patients who had successful coronary angioplasty 6 to 30 mo (mean 10.7) prior to restudy. Restenosis was found in 43 of 140 dilated lesions (31%) and in 41 of 94 patients (44%). Thirty-three (35%) patients had new or progressive lesions outside the angioplasty site. New or progressive lesions occurred with similar frequency in the arteries that did not have angioplasty (23/155 = 15%) as in the arteries that did (13/127 = 10%; chi-square n.s.). In the arteries which underwent angioplasty, new or progressive lesions occurred as commonly proximal to the PTCA site (7/14, 50%) as distal (6/13, 46%). New or progressive lesions occurred in 29% of patients with concomitant restenosis, and 40% of those without restenosis (chi-square n.s.). No clinical, angiographic, or procedural factors distinguished patients with new and progressive lesions in target vessels from those without these lesions in target vessels. Patients with progressive lesions anywhere in the coronary tree were more likely to have had a shorter duration of anginal symptoms before angioplasty and a family history of coronary disease when compared with patients without progressive atherosclerosis. In conclusion, new and progressive lesions outside the angioplasty site occur after the procedure but appear unrelated to the restenosis process or traumatic injury by angioplasty instrumentation. .A Nguyen KP; Shaw RE; Myler RK; Webb JG; Stertzer SH. .I 274617 .U 91004194 .S Cathet Cardiovasc Diagn 9101; 21(1):10-2 .M Acute Disease; Case Report; Diagnosis, Differential; Electrocardiography; Female; Heart Catheterization; Human; Middle Age; Myocardial Infarction/*DI; Myocarditis/*DI/PA; Myocardium/PA. .T Myocarditis simulating acute transmural myocardial infarction. .P JOURNAL ARTICLE. .W A patient with cardiogenic shock had typical electrocardiographic findings of acute anterior transmural myocardial infarction. Cardiac catheterization revealed normal coronary arteries and severe biventricular failure. Postmortem examination confirmed normal coronary arteries; acute myocarditis, but no evidence for infarction, was found. Electrocardiographic changes of myocarditis may be indistinguishable from acute transmural infarction. In suspected cases, cardiac catheterization should be considered prior to thrombolytic therapy. .A Chakko S; Woska D; de Marchena E; Morales AR; Castellanos A. .I 274618 .U 91004195 .S Cathet Cardiovasc Diagn 9101; 21(1):13-4 .M Aged; Aorta, Thoracic; Brachiocephalic Veins/*IN; Case Report; Catheterization, Swan-Ganz/*AE; Cineangiography; Human; Jugular Veins/*; Male. .T Misplacement of a Swan-Ganz catheter after insertion through the left internal jugular vein. .P JOURNAL ARTICLE. .W We report a case of perforation of the left brachiocephalic vein after insertion through the left internal jugular vein. Entrapment of air in the balloon occurred, possibly due to high surrounding tissue pressure at its base, preventing deflation. We emphasize the potential hazards of catheterization via the left internal jugular vein. .A Unger P; Stoupel E; Berkenboom G. .I 274619 .U 91004196 .S Cathet Cardiovasc Diagn 9101; 21(1):15-7 .M Aged; Angioplasty, Transluminal/IS/*MT; Case Report; Catheterization/IS; Female; Femoral Artery/*; Human; Intermittent Claudication/*TH; Male; Middle Age. .T Use of a guiding catheter for contralateral femoral artery angioplasty. .P JOURNAL ARTICLE. .W We describe a unique method employing a transseptal sheath as a "guiding catheter" that allows contralateral retrograde femoral artery access to perform balloon angioplasty of proximal superficial femoral artery lesions. This technique simplifies arterial access, provides support for crossing lesions, and allows angiographic visualization of target lesions during the procedure. .A White CJ; Nguyen M; Ramee SR. .I 274620 .U 91004197 .S Cathet Cardiovasc Diagn 9101; 21(1):18-22 .M Adult; Balloon Dilatation/*; Case Report; Echocardiography; Female; Human; Implants, Artificial; Mitral Valve/SU; Mitral Valve Insufficiency/*SU; Mitral Valve Stenosis/*TH/US. .T Percutaneous valvuloplasty in a patient with mitral stenosis following surgical annuloplasty. .P JOURNAL ARTICLE. .W A case is described in which a patient with a Carpentier-Edwards annuloplasty ring developed mitral stenosis and was treated with percutaneous mitral valvuloplasty. Possible mechanisms for the development of mitral stenosis are briefly discussed. .A Saenz CB; Nocero MA; Weaver CJ. .I 274621 .U 91004198 .S Cathet Cardiovasc Diagn 9101; 21(1):23-5 .M Aged; Angiography; Angioplasty, Transluminal, Percutaneous Coronary/*; Case Report; Coronary Arteriosclerosis/*SU/TH; Coronary Vessels/RA/*SU; Emergencies; Human; Male; Myocardial Infarction/TH; Recurrence; Shock, Cardiogenic/*SU/TH; Vascular Patency. .T Salvage from cardiogenic shock by atherectomy after failed emergency coronary artery angioplasty. .P JOURNAL ARTICLE. .W In this case report of a patient undergoing angioplasty for cardiogenic shock during acute myocardial infarction, recurrent occlusion resulted in recurrence of shock. Atherectomy reestablished lasting patency and reversed the patient's hemodynamic collapse. Atherectomy deserves further investigation as a means to salvage vessel patency during unsuccessful coronary angioplasty. .A Smucker ML; Sarnat WS; Kil D; Scherb DE; Howard PF. .I 274622 .U 91004199 .S Cathet Cardiovasc Diagn 9101; 21(1):26-7 .M Aged; Balloon Dilatation/*AE; Cardiopulmonary Bypass/*MT; Case Report; Heart Injuries/*ET/TH; Heart Ventricle/IN; Human; Male; Mitral Valve Stenosis/*TH. .T Left ventricular rupture complicating percutaneous mitral commissurotomy: salvage using percutaneous cardiopulmonary bypass support. .P JOURNAL ARTICLE. .W Left ventricular rupture resulting in death has been reported to be a complication of percutaneous mitral commissurotomy. We report a 71-year-old man in whom a left ventricular rupture occurred during percutaneous mitral commissurotomy and resulted in hemodynamic collapse due to acute cardiac tamponade. The patient was stabilized using percutaneously instituted cardiopulmonary bypass support with subsequent repair of the left ventricle and successful mitral valve replacement. Three months later this patient remains in New York Heart Class I. .A Shawl FA; Domanski MJ; Yackee JM; Wish MH; Dullum M; Neimat S. .I 274623 .U 91004200 .S Cathet Cardiovasc Diagn 9101; 21(1):28-40 .M Arteriovenous Fistula/EP/RA; Coronary Vessel Anomalies/*EP/RA; Coronary Vessels/*RA; Female; Human; Incidence; Male; Middle Age; Ohio/EP; Pulmonary Artery/AB. .T Coronary artery anomalies in 126,595 patients undergoing coronary arteriography. .P JOURNAL ARTICLE. .W Coronary artery anomalies were found in 1,686 patients (1.3% incidence) undergoing coronary arteriography at the Cleveland Clinic Foundation from 1960 to 1988. Of the 1,686 patients, 1,461 (87%) had anomalies of origin and distribution, and 225 (13%) had coronary artery fistulae. Most coronary anomalies did not result in signs, symptoms, or complications, and usually were discovered as incidental findings at the time of catheterization. Eighty-one percent were "benign" anomalies: 1) separate origin of the left anterior descending and circumflex from the left sinus of Valsalva; 2) ectopic origin of the circumflex from the right sinus of Valsalva; 3) ectopic coronary origin from the posterior sinus of Valsalva; 4) anomalous coronary origin from the ascending aorta; 5) absent circumflex; 6) intercoronary communications; and 7) small coronary artery fistulae. Other anomalies may be associated with potentially serious sequelae such as angina pectoris, myocardial infarction, syncope, cardiac arrhythmias, congestive heart failure, or sudden death. Potentially serious anomalies include: 1) ectopic coronary origin from the pulmonary artery; 2) ectopic coronary origin from the opposite aortic sinus; 3) single coronary artery; and 4) large coronary fistulae. Coronary artery anomalies require accurate recognition, and at times, surgical correction. .A Yamanaka O; Hobbs RE. .I 274624 .U 91004201 .S Cathet Cardiovasc Diagn 9101; 21(1):41-4 .M Case Report; Coronary Vessels/*RA; Electrocardiography/*; Female; Heart Catheterization; Human; Middle Age; Myocardial Infarction/*DI/RA. .T Reciprocal ECG changes in acute myocardial infarction and angiographic correlation [clinical conference] .P CLINICAL CONFERENCE; JOURNAL ARTICLE. .A Porter TR; Vetrovec GW. .I 274625 .U 91004202 .S Cathet Cardiovasc Diagn 9101; 21(1):45-50 .M Angioplasty, Transluminal, Percutaneous Coronary/*IS/MO; Animal; Comparative Study; Coronary Circulation/*PH; Coronary Disease/PC; Coronary Vessels/*; Dogs; Electrocardiography; Female; Male; Support, Non-U.S. Gov't. .T Left main percutaneous transluminal coronary angioplasty with the autoperfusion catheter in an animal model. .P JOURNAL ARTICLE. .W Left main coronary angioplasty is associated with high risk because of interruption of blood flow to much of the left ventricle during balloon inflation. An "autoperfusion" balloon angioplasty catheter that allows blood to flow passively distal to an inflated balloon was tested in dogs and compared with inflations with standard balloon catheters. During 3 min occlusions of the left main coronary artery with the autoperfusion catheter, regional myocardial blood flow was preserved at 0.60 +/- 0.14 ml/min/g, compared with 0.07 +/- 0.03 ml/min/g during inflation with standard balloon catheters (P less than 0.01). Similarly, at the end of 3 min of inflation, left ventricular systolic pressure and dP/dt were maintained with autoperfusion catheter inflation, but they were severely depressed after standard angioplasty balloon inflation. All seven dogs survived autoperfusion balloon inflation, whereas five of seven developed sustained ventricular tachycardia and/or ventricular fibrillation during or after standard balloon inflation. Thus, distal blood flow, hemodynamics, and survival were preserved during autoperfusion balloon inflation in the left main coronary artery. .A Turi ZG; Rezkella S; Campbell CA; Kloner RA. .I 274626 .U 91004203 .S Cathet Cardiovasc Diagn 9101; 21(1):51-4 .M Aged; Angiography/MT; Aortic Valve Stenosis/*DI; Coronary Vessels; Fluoroscopy; Heart Catheterization/IS/*MT; Human; Support, U.S. Gov't, P.H.S.. .T A rapid, effective technique for retrograde crossing of valvular aortic stenosis using standard coronary catheters [see comments] .P JOURNAL ARTICLE. .W Retrograde crossing of valvular aortic stenosis can be challenging even to experienced angiographers. In 446 of 447 consecutive patients with aortic stenosis catheterized during the past 3 years, a technique using a standard Judkins right coronary catheter and a floppy straight tipped guide wire was successful in rapidly and efficiently crossing these pathologically distorted valves in retrograde fashion. Once the valve was crossed, the coronary catheter was replaced with a pigtail catheter for pressure and ventriculography. The majority of these valves required less than 2 min to cross using this technique. This method is valuable in limiting the time required for catheterization, thus helping to reduce procedure related morbidity in these oftimes critically ill patients. .A Harrison JK; Davidson CJ; Phillips HR; Harding MB; Kisslo KB; Bashore TM. .I 274627 .U 91004204 .S Cathet Cardiovasc Diagn 9101; 21(1):55-7 .M Angiography/*AE; Case Report; Catheterization/*AE/IS; Coronary Vessels/*RA; Human; Iliac Artery/*IN; Male; Middle Age. .T A new complication of coronary arteriography. .P JOURNAL ARTICLE. .W The introduction of a sharply angulated catheter through an arterial sheath for percutaneous coronary arteriography was associated in 7 cases with dissection of the iliac arteries; this extended to the lumbar aorta at the level of the coeliac axis. The catheter tip should be introduced gently and preferably straightened out with a good length of guide wire to avoid this complication. .A Raphael MJ; Donaldson RM. .I 274628 .U 91004205 .S Cathet Cardiovasc Diagn 9101; 21(1):58-60 .M Cineradiography/*ST; Heart/*RA; Human; Videotape Recording/*ST. .T Interim standard: videotape recorders for transferring cardiac cinefluorographic studies. Laboratory Performance Standards Committee, the Society for Cardiac Angiography and Interventions. .P GUIDELINE; JOURNAL ARTICLE. .I 274629 .U 91004206 .S Cathet Cardiovasc Diagn 9101; 21(1):63 .M Aged; Case Report; Female; Heart Atrium; Heart Catheterization/*; Heart Neoplasms/*; Human; Myxoma/*. .T Transseptal left atrial catheterization [letter] .P LETTER. .A Henderson MA. .I 274630 .U 91004207 .S Cathet Cardiovasc Diagn 9101; 21(1):7-9 .M Aged; Balloon Dilatation/*AE; Case Report; Echocardiography, Doppler; Electrocardiography; Female; Heart Catheterization; Human; Lutembacher's Syndrome/*ET/US; Mitral Valve Stenosis/*TH; Rheumatic Heart Disease/*TH; Time Factors. .T Acquired Lutembacher syndrome or mitral stenosis and acquired atrial septal defect after transseptal mitral valvuloplasty. .P JOURNAL ARTICLE. .W Critical mitral stenosis in selected patients may be treated successfully with percutaneous mitral valvuloplasty. Complications of this procedure, particularly an atrial septal defect following transseptal approach, are generally of minor clinical significance. We describe a woman who initially underwent a successful percutaneous double-balloon mitral valvuloplasty via the transseptal approach. Three months later she presented with right-sided heart failure. Color Doppler echocardiography and cardiac catheterization demonstrated an atrial septal defect (ASD) as well as restenosis of the mitral valve. We conclude that significant ASDs may occur following transseptal mitral valvuloplasty with appearance of right ventricular failure and that color Doppler imaging aids in the diagnosis of this new variant of the classical Lutembacher syndrome. .A Sadaniantz A; Luttmann C; Shulman RS; Block PC; Schachne J; Thompson PD. .I 274631 .U 91004536 .S Can J Anaesth 9101; 37(6):603-7 .M Anesthesia, Inhalation/*HI/IS; Animal; Heart/DE; Heart Diseases/PP; History of Medicine, 19th Cent.; History of Medicine, 20th Cent.; Human; Nitrous Oxide/*HI/PD. .T Nitrous oxide 1844-1990 [editorial; comment] .P COMMENT; EDITORIAL; HISTORICAL ARTICLE. .A O'Connor JP. .I 274632 .U 91004537 .S Can J Anaesth 9101; 37(6):608-12 .M Analgesia, Epidural/*/AE; Cesarean Section/*AE; Female; Human; Morphine/*AD/AE; Pain, Postoperative/*PC; Pregnancy. .T Epidural morphine for post-caesarean analgesia [editorial; comment] .P COMMENT; EDITORIAL. .A Writer WD. .I 274633 .U 91004538 .S Can J Anaesth 9101; 37(6):613-7 .M Adult; Aged; Anesthesia, Inhalation/*; Blood Pressure/DE; Cardiac Output/DE; Heart Rate/DE; Heart Valve Diseases/PP/SU; Human; Hypertension, Pulmonary/*PP; Middle Age; Mitral Valve/*/SU; Nitrous Oxide/AD/*PD; Pulmonary Artery; Pulmonary Circulation/*DE; Pulmonary Wedge Pressure/DE; Stroke Volume/DE; Vascular Resistance/DE; Ventricular Function/*DE. .T Nitrous oxide does not exacerbate pulmonary hypertension or ventricular dysfunction in patients with mitral valvular disease [see comments] .P JOURNAL ARTICLE. .W Using the rapid-response thermistor pulmonary artery catheter and transoesophageal echocardiography, this study examined the effects of 100 per cent oxygen, 70 per cent nitrous oxide/30 per cent oxygen, and 70 per cent nitrogen/30 per cent oxygen on the pulmonary circulation and ventricular function in ten patients with pulmonary hypertension. In comparison with baseline measurements, nitrous oxide administration resulted in small but statistically significant (P less than 0.05) changes in mean arterial pressure (76 +/- 14 to 67 +/- 12), mean pulmonary arterial pressure (37 +/- 14 to 33 +/- 13 mmHg), and cardiac output (3.7 +/- 1.4 to 3.2 +/- 1.1 L.min-1). Seventy per cent nitrogen resulted in no significant changes from baseline. The repeat 100 per cent oxygen measurements were nearly identical to the nitrous oxide measurements. It is concluded that nitrous oxide does not exacerbate pulmonary hypertension or ventricular dysfunction during high-dose fentanyl anaesthesia in patients with mitral valvular disease. .A Konstadt SN; Reich DL; Thys DM. .I 274634 .U 91004541 .S Can J Anaesth 9101; 37(6):629-35 .M Adolescence; Adult; Aged; Anesthesia Recovery Period; Anesthesia, Intravenous/*; Anesthetics; Blood Pressure/DE; Cholecystectomy/*; Female; Fentanyl/*AA/AD/AE/BL/PD; Heart/DE; Heart Rate/DE; Human; Isoflurane/AD; Male; Middle Age; Pain, Postoperative/PC; Respiratory Insufficiency/ET; Support, Non-U.S. Gov't; Time Factors. .T Low-dose sufentanil in major surgery. .P JOURNAL ARTICLE. .W The purpose of this study was to assess the efficacy of sufentanil 1 micrograms.kg-1 during N2O-O2 and intermittent isoflurane anaesthesia in major non-cardiac surgery. Thirty-one patients (18 females, 13 males; mean age 47 yr), undergoing cholecystectomy received a 1 microgram.kg-1 bolus of sufentanil before the induction of anaesthesia with thiopentone. On average, three sufentanil increments were administered, to a total (bolus + maintenance) dose of 1.5 micrograms.kg-1. Cardiovascular stability was not achieved in eleven patients who then were given isoflurane. The arterial pressure decreased after sufentanil (P less than 0.05), reaching a nadir (mean 108/65 mmHg, heart rate 63 bpm) at one minute post-incision. Clinically important hypertension or hypotension did not occur in any patient. One patient, receiving beta-blocker therapy, required atropine to control bradycardia. Postoperative respiratory depression did not occur in patients who received less than one micrograms.kg-1.hr-1 with the last increment being given more than 20 minutes before the end of anaesthesia. Slight respiratory depression in the recovery room was reported in one patient, who had received a total of 1.3 micrograms.kg-1.hr-1 of sufentanil, and the last sufentanil increment 24 min before the end of surgery. The most frequently reported side-effects were nausea (35 per cent) and vomiting (23 per cent). Induction, maintenance and recovery from anaesthesia were rated as "good" in 87, 87, and 74 per cent of the cases, respectively, and "satisfactory" in the remainder. We conclude that this technique is valuable to assure good protection of the cardiovascular system without undue respiratory depression during recovery. .A Perreault L; Vezina D; Roberts K; Baillargeon R. .I 274635 .U 91004542 .S Can J Anaesth 9101; 37(6):636-40 .M Acetaminophen/TU; Adult; Analgesia, Epidural/*; Anesthesia, Epidural; Anesthesia, Obstetrical; Cesarean Section/*AE; Dizziness/CI; Female; Human; Morphine/AD/AE/*TU; Nausea/CI; Pain, Postoperative/*PC; Pregnancy; Respiratory Insufficiency/CI; Retrospective Studies; Time Factors; Vomiting/CI. .T Epidural morphine for analgesia after caesarean section: a report of 4880 patients [see comments] .P JOURNAL ARTICLE. .W This retrospective study was undertaken to assess the efficacy and safety of epidural morphine in providing analgesia following Caesarean section under epidural anaesthesia. The morphine was administered as a single bolus, following delivery, in doses ranging from 2 to 5 mg. The charts of 4880 Caesarean sections, performed on 4500 patients, were reviewed. The duration of analgesia and the occurrence of any symptoms which might be side-effects of the epidural morphine were recorded. The duration of analgesia was 22.9 +/- 10.1 hr and was not correlated with the dose of epidural morphine. Eleven per cent of the patients required no supplemental analgesia during the first 48 hr. Twelve patients (0.25 per cent) had respiratory rates less than 10 breaths per minute, on at least one occasion. No serious sequelae resulted from these periods of bradypnoea. Pruritus occurred in 58 per cent of patients, nausea and vomiting in 39.9 per cent and dizziness in ten per cent. Herpes simplex labialis was recorded in 3.5 per cent of patients. Epidural morphine is thus confirmed as an effective analgesic technique post-Caesarean section with 3 mg being the optimal dose. Even in this young healthy patient population, clinically detectable respiratory depression occurs so clinical respiratory monitoring is indicated. .A Fuller JG; McMorland GH; Douglas MJ; Palmer L. .I 274636 .U 91004543 .S Can J Anaesth 9101; 37(6):641-4 .M Adult; Anesthesia, General/*; Anesthesia, Obstetrical/*; Apgar Score; Awareness/*DE; Blood Gas Analysis; Blood Pressure/DE; Cesarean Section/*/MT; Delivery; Female; Fetal Blood/CH; Heart Rate/DE; Human; Infant, Newborn; Ketamine/*PD; Pregnancy; Pregnancy Outcome/*; Respiration/DE; Time Factors; Umbilical Veins. .T Maternal awareness and neonatal outcome after ketamine induction of anaesthesia for Caesarean section. .P JOURNAL ARTICLE. .W Ketamine was used as the sole anaesthetic during the induction-to-delivery interval in 20 full-term patients undergoing elective Caesarean section. The intravenous administration of ketamine 1.5 mg.kg-1 was followed by succinylcholine 1.5 mg.kg-1 and tracheal intubation. The mother's lungs were then ventilated using 100 per cent oxygen until the baby was delivered. Intraoperative maternal awareness was assessed by the isolated forearm technique. The Apgar scores of the newborn at one and five minutes, as well as their umbilical vein blood gases were also evaluated and correlated with the induction-to-delivery (I-D) and the uterine incision-to-delivery (U-D) intervals. In 13 patients (Group A) the I-D interval was less than 10 min and U-D interval less than 90 sec, while in seven (Group B) the I-D interval was greater than or equal to 10 min and the U-D interval greater than or equal to 90 sec. The isolated arm test was negative in all patients having an I-D interval less than 10 min, and was positive in three patients when the I-D interval exceeded ten minutes. The newborns of group A showed higher Apgar scores at one minute, as well as higher umbilical vein PO2 than was achieved in Group B. It was concluded that the technique used was not associated with maternal awareness or neonatal depression, provided that the I-D interval was less than 10 min and the U-D interval was less than 90 sec. .A Baraka A; Louis F; Dalleh R. .I 274637 .U 91004544 .S Can J Anaesth 9101; 37(6):645-9 .M Adult; Anesthesia, General/*; Blood Glucose/*ME; Blood Pressure/PH; Catecholamines/BL; Central Venous Pressure/PH; Fatty Acids, Nonesterified/BL; Female; Glucagon/BL; Glucose/*ME; Glucose Clamp Technique; Human; Insulin/BL; Male; Surgery, Minor; Surgery, Operative/*; Time Factors. .T Decreased glucose utilization during prolonged anaesthesia and surgery. .P JOURNAL ARTICLE. .W We studied the influence of prolonged anaesthesia and surgery on glucose metabolism by means of the euglycaemic insulin clamp method in eight patients who underwent prolonged surgery. Eleven patients who underwent surgery of short duration served as a control group. Plasma concentrations of catabolic hormones were measured simultaneously. Glucose utilization during prolonged anaesthesia, (PA) group, was lower than that in the control group (P less than 0.01) (glucose utilization 7.59 +/- 0.73 mg.kg-1.hr-1 in the control group vs 4.03 +/- 0.71 mg.kg-1.hr-1 in PA group respectively). There were no significant differences in plasma catecholamine and glucagon concentrations between the PA and control groups. Plasma-free fatty acid levels increased significantly in the PA group before the euglycaemic insulin clamp (free fatty acid level: 0.496 +/- 0.053 mmol.L-1 in the control group, vs 0.834 +/- 0.103 mmol.L-1 in the PA group at the pre-clamp period, P less than 0.01). Tissue resistance to exogenous insulin increased during prolonged anaesthesia and surgery although there were no significant changes in plasma catabolic hormone levels. .A Tsubo T; Kudo T; Matsuki A; Oyama T. .I 274638 .U 91004545 .S Can J Anaesth 9101; 37(6):650-5 .M Administration, Oral; Adolescence; Adult; Aged; Antacids/AD/AN/*TU; Citrates/AD/AN/*TU; Drug Combinations; Fasting; Gastric Acid/PH; Gastric Juice/*PH/SE; Gastrointestinal Contents; Human; Hydrogen-Ion Concentration; Metoclopramide/AD/*TU; Middle Age; Ranitidine/AD/*TU; Spectrophotometry; Support, Non-U.S. Gov't; Surgery, Operative/*; Time Factors. .T Gastric fluid volume and pH in elective surgical patients: triple prophylaxis is not superior to ranitidine alone. .P JOURNAL ARTICLE. .W The effect of oral ranitidine alone was compared with sequentially administered ranitidine, metoclopramide, and sodium citrate on gastric fluid volume and pH in 196 healthy, elective surgical inpatients, each of whom was randomly assigned to one of four groups. Patients in all groups received oral ranitidine 150 mg 2-3 hr before the scheduled time of surgery. Those in Group 1 also received oral metoclopramide 10 mg one hour before surgery, and sodium citrate 0.3 M 30 ml on call to the operating room; Group 2 received sodium citrate but no metoclopramide; Group 3 received metoclopramide but no sodium citrate; Group 4 received ranitidine alone. Following induction of anaesthesia a #18 Salem sump tube was passed into the stomach and all available gastric fluid was aspirated. Volumes were recorded and pH measured. In all groups mean pH was greater than 5.8, although at least one patient in each group had pH less than 2.5. Mean volumes were significantly greater in patients who received citrate (Groups 1 and 2: 22 and 19 ml) than in those in those who did not (Groups 3 and 4: 10 and 8 ml). One patient in Group 2 and one in Group 3 had pH less than 2.5 with volume greater than 25 ml. Our results do not demonstrate any advantage of double or triple prophylaxis over ranitidine alone. The practical difficulty of correctly administering two or even three medications, each at different but exact preoperative intervals, is emphasized. .A Maltby JR; Elliott RH; Warnell I; Fairbrass M; Sutherland LR; Shaffer EA. .I 274639 .U 91004546 .S Can J Anaesth 9101; 37(6):656-8 .M Administration, Cutaneous; Aerosols; Ambulatory Surgery; Analysis of Variance; Anesthesia, Local/*; Bloodletting/*AE/IS; Catheterization, Peripheral/IS; Comparative Study; Ethyl Chloride/*/AD; Female; Human; Injections, Intradermal; Lidocaine/*/AD; Pain/*PC; Support, Non-U.S. Gov't. .T Ethyl chloride and venepuncture pain: a comparison with intradermal lidocaine. .P JOURNAL ARTICLE. .W One hundred and twenty unpremedicated patients undergoing gynaecological surgery were randomly allocated to one of three equal treatment groups to assess the effectiveness of ethyl chloride in producing instant skin anaesthesia to prevent the pain of venepuncture from a 20 G cannula. They received either no anaesthetic, 0.2 ml one per cent lidocaine plain intradermally or a ten-second spray of ethyl chloride at the cannulation site. Ethyl chloride produced skin anaesthesia that significantly reduced the pain of venepuncture. However, it was not as effective as intradermal lidocaine. It had no effect on vein visualisation or ease of cannulation. Ethyl chloride can be recommended as a method of producing instant skin anaesthesia. .A Armstrong P; Young C; McKeown D. .I 274640 .U 91004547 .S Can J Anaesth 9101; 37(6):659-62 .M Analysis of Variance; Anesthesia, General/*; Axilla; Body Temperature/*/PH; Cardiopulmonary Bypass/*; Equipment Design; Esophagus; Forehead/*; Human; Hypothermia, Induced; Middle Age; Monitoring, Physiologic; Rectum; Regression Analysis; Skin Temperature/*/PH; Support, Non-U.S. Gov't; Thermometers/*; Time Factors. .T Does forehead liquid crystal temperature accurately reflect "core" temperature? .P JOURNAL ARTICLE. .W Liquid crystal thermometry (LCT) is a non-invasive alternative to temperature monitoring. We evaluated the ability of forehead LCT, rectal temperature, and axillary skin temperature to trend distal oesophageal temperature during rapid warming on cardiopulmonary bypass. In 24 patients undergoing open heart surgery, temperatures were measured during the rapid warming phase on bypass (12-35 min). Scattergrams of temperature vs time for the four temperature sites each contained 150 data points. Polynomial regression analysis revealed that LCT, but not axillary or rectal temperatures, correlated with oesophageal temperature. We conclude that forehead LCT may be useful to monitor temperature trends and to detect rapid elevations in body temperature when more invasive temperature monitoring is inappropriate or unavailable. .A Allen GC; Horrow JC; Rosenberg H. .I 274641 .U 91004548 .S Can J Anaesth 9101; 37(6):663-71 .M Anesthesia; Brain/DE/ME/*PP; Brain Injuries/ME/*PP; Cerebral Ischemia/ME/*PP; Cerebrovascular Circulation/PH; Heart Surgery; Human. .T Brain protection: physiological and pharmacological considerations. Part I: The physiology of brain injury. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Ischaemia, whether focal or global in nature, produces a sequence of intracellular events leading to increased cell permeability to water and ions including Ca++. There is a loss of cellular integrity and function, with increased production of prostaglandins, free radicals, and acidosis with lactate accumulation. These events may be exacerbated by glucose administration. Pharmacological agents aimed at alleviating ischaemic injury could be directed at decreasing cerebral metabolic requirements for oxygen, improving flow to ischaemic areas, preventing Ca+(+)-induced injury, inhibition of free radical formation, lactate removal, inhibition of prostaglandin synthesis, and prevention of complement-mediated leukocyte aggregation. Part I of this paper describes some of the pathophysiological events leading to ischaemic brain injury. Part 2 of this paper will consider the current agents available for brain protection. .A Murdoch J; Hall R. .I 274642 .U 91004549 .S Can J Anaesth 9101; 37(6):672-4 .M Cardiac Pacing, Artificial/*MT; Case Report; Esophagus; Fistula/SU; Human; Infant, Newborn; Intraoperative Complications/*TH; Recurrence; Spinal Cord Diseases/SU; Tachycardia, Paroxysmal/*TH; Tachycardia, Supraventricular/*TH. .T Transoesophageal pacing for perioperative control of neonatal paroxysmal supraventricular tachycardia. .P JOURNAL ARTICLE. .W The perioperative management of a 16-day-old infant with recurrent supraventricular tachycardia (SVT) is discussed. Vagal manoeuvres and medication were not adequate in controlling the SVT. Since the patient was scheduled for extensive surgery in the prone position, it was decided to use transoesophageal pacing as the method of choice for conversion of SVT. Transoesophageal pacing succeeded several times in overriding the SVT and restoring normal heart rate and haemodynamic variables. The advantages and disadvantages of various methods of treating SVT in the newborn are discussed. .A Stevenson GW; Schuster J; Kross J; Hall SC. .I 274643 .U 91004551 .S Can J Anaesth 9101; 37(6):678-9 .M Adult; Analgesia, Epidural; Anesthesia, Epidural/*; Anesthesia, Obstetrical/*; Case Report; Female; Herpes Gestationis/*CO; Human; Pregnancy; Pregnancy Complications/*. .T Epidural analgesia for a parturient with herpes gestationis. .P JOURNAL ARTICLE. .W A 23-yr-old parturient with herpes gestationis spontaneously delivered a normal healthy infant under epidural analgesia. She received five injections of bupivacaine 0.5 per cent over a ten-hour period. There was no infection at the lumbar region, even though her body was covered with vesicles and bullae including the face and neck. Eight months after delivery the patient still has a vesicular eruption which occurs mainly during her menses. .A Eldor J; Zlotogorski A; Meirow D; Cohen M. .I 274644 .U 91004552 .S Can J Anaesth 9101; 37(6):680-4 .M Adult; Analgesia, Epidural; Anesthesia, Epidural/*; Anesthesia, Obstetrical/*; Case Report; Cesarean Section/*; Female; Heart Defects, Congenital/*CO; Heart Ventricle/AB; Human; Labor, Induced/*; Pain, Postoperative/PC; Pregnancy; Pregnancy Complications, Cardiovascular/*; Transposition of Great Vessels/*CO. .T Epidural anaesthesia for labour and caesarean section in a parturient with a single ventricle and transposition of the great arteries. .P JOURNAL ARTICLE; REVIEW; REVIEW OF REPORTED CASES. .W We describe a case of a 29-year-old parturient with a single ventricle and transposition of the great arteries who had lumbar epidural analgesia/anaesthesia with a local anaesthetic for labour, emergency Caesarean section and postoperative pain. Her outcome and that of her baby was successful. The anaesthetic techniques used in other parturients with similar congenital cardiac anomalies are reviewed. .A Fong J; Druzin M; Gimbel AA; Fisher J. .I 274645 .U 91004554 .S Can J Anaesth 9101; 37(6):689 .M Anesthesiology/HI; Canada; History of Medicine, 20th Cent.; Manitoba; Portraits. .T Beverly Charles Leech (1898-1960). .P HISTORICAL ARTICLE; HISTORICAL BIOGRAPHY; JOURNAL ARTICLE. .A Shephard DA. .I 274646 .U 91004555 .S Can J Anaesth 9101; 37(6):690-4 .M Carbon Radioisotopes/DU; Choline Acetyltransferase/AI/*ME; Dose-Response Relationship, Drug; Ion Exchange Resins; Pancuronium/AD/*PD; Regression Analysis; Succinylcholine/AD/*PD; Support, Non-U.S. Gov't; Tubocurarine/AD/*PD; Vecuronium/AD/*PD. .T Pancuronium, vecuronium, and d-tubocurarine inhibit and succinylcholine stimulates choline acetyltransferase activity. .P JOURNAL ARTICLE. .W The effects of the nondepolarizing muscle relaxants (NDMR), pancuronium, vecuronium, and d-tubocurarine and a depolarizing muscle relaxant, succinylcholine, were studied on choline acetyltransferase (ChAT) activity. A radiochemical assay was used in the determination of ChAT activity using purified placental enzyme. Pancuronium at concentrations of 10(-7) M, 10(-6) M, 10(-5) M, 10(-4) M, and 10(-3) M inhibited ChAT activity by 3, 10, 15, 40 and 85 per cent, respectively; vecuronium at concentrations of 10(-6) M, 10(-5) M, 10(-4) M, and 10(-3) M inhibited ChAT activity by 5, 10, 26 and 57 per cent, respectively; d-tubocurarine at concentrations of 10(-6) M, 10(-5) M, 10(-4) M, and 10(-3) M inhibited ChAT activity by 0, 4, 12.5 and 29 per cent, respectively; whereas succinylcholine at concentrations of 10(-7) M, 10(-6) M, 10(-5) M, and 10(-4) M activated ChAT activity by 8, 10, 1, and 2 per cent, respectively. Even though our present data demonstrated a significant dose-dependent inhibitory effect on ChAT activity by pancuronium, vecuronium and d-tubocurarine, it is unlikely that this inhibitory effect will contribute to the mechanism of action of NDMR. Our data, however, may suggest an additional mechanism for the phenomena of tetanic and train-of-four fades that are seen following the administration of nondepolarizing muscle relaxants. .A Kambam JR; Janson VE; Day P; Sastry BV. .I 274647 .U 91004556 .S Can J Anaesth 9101; 37(6):695-8 .M Caffeine/AE; Calcium/*PD; Contracture/*PP; Drug Interactions; Halothane/AE; Human; In Vitro; Malignant Hyperthermia/*PP; Muscle Contraction/*DE/PH; Muscles/DE/PP; Nifedipine/PD; Quinacrine/PD; Strontium/PD; Succinylcholine/AE; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Verapamil/PD. .T The importance of calcium ions for in vitro malignant hyperthermia testing. .P JOURNAL ARTICLE. .W Intracellular Ca++ levels in skeletal muscle are elevated during the in vitro contracture response of muscle from subjects with malignant hyperthermia. The role of Ca++ in the bathing medium and the consequences of substitution of Sr++ for Ca++ in the response to agents associated with malignant hyperthermia were examined. When Ca++ was omitted from the bathing medium the contractures induced in human vastus lateralis by halothane (three per cent) or succinylcholine (50 mM) were reduced by 80 and 100 per cent, respectively, while contractures induced by caffeine (8 mM) were only reduced by 50 per cent. Substitution of Ca++ by another divalent cation, Sr++, completely restored contractures induced by caffeine, but only partially restored contractures induced by halothane or succinylcholine (to 50 and 30 per cent of Ca(++)-containing medium, respectively). Mepacrine (10 microM) was effective in antagonizing contractures by caffeine, whereas verapamil and nifedipine (10 microM) were not. These results support an essential role for extracellular Ca++ not fulfilled by Sr++ in contracture induction by halothane and succinylcholine, but not by caffeine. .A Fletcher JE; Huggins FJ; Rosenberg H. .I 274648 .U 91004557 .S Can J Anaesth 9101; 37(6):699-704 .M Ambulatory Surgery/*SN; Anesthesia/SN; Canada/EP; Diagnosis; Hemorrhage/EP; Hospitals, General/*SN; Human; Outpatient Clinics, Hospital/*; Patient Admission/*SN; Patient Discharge/SN; Postoperative Complications/EP; Syncope/EP. .T Hospital admissions from the Surgical Day Care Centre of Vancouver General Hospital 1977-1987. .P JOURNAL ARTICLE. .W The admissions to Vancouver General Hospital from its Surgical Day Care Centre were reviewed for the period 1977 to 1987. The overall mean rate of admission for the period was 0.28 per cent, for surgically-related admissions 0.22 per cent and for anaesthesia-related admissions 0.07 per cent. The principal reasons for surgery-related admissions were postoperative bleeding, complications, the need for further surgery, the requirement for prolonged postoperative care, and pain. Urology had a particularly high percentage of admissions compared with its workload, because of the diagnostic nature of much of the work. Anaesthesia-related admissions included "syncope," lack of an accompanying adult, aspiration pneumonitis and coincident acute disease. Twelve of the 14 patients admitted with syncope had surgery in the afternoon and had received less than ideal amounts of intravenous fluid. Seven of the 12 ASA physical status II patients admitted had an admission diagnosis related to the coincident disease. .A Fancourt-Smith PF; Hornstein J; Jenkins LC. .I 274649 .U 91004558 .S Can J Anaesth 9101; 37(6):705 .M Analgesia/*MT; Bupivacaine/AD/*TU; Case Report; Catheterization; Chest Pain/DT; Human; Male; Middle Age; Pleura; Rib Fractures/*TH. .T Continuous infusion interpleural analgesia for multiple fractured ribs [letter] .P LETTER. .A Hudes ET. .I 274650 .U 91004559 .S Can J Anaesth 9101; 37(6):705-6 .M Cricoid Cartilage; Human; Intubation, Intratracheal/*; Thyroid Cartilage; Tracheotomy. .T Failed intubation [letter] .P LETTER. .I 274651 .U 91004561 .S Can J Anaesth 9101; 37(6):707 .M Anesthesia, Closed-Circuit/*IS; Anesthesia, Inhalation/*IS; Equipment Design; Equipment Failure; Human. .T Breathing circuit occlusion due to defect in swivel port connector [letter] .P LETTER. .A Ananthanarayan C; Urbach G; Tincombe C; Smith R; Marshall-Hanasyk S. .I 274652 .U 91004562 .S Can J Anaesth 9101; 37(6):707-9 .M Cervical Vertebrae/*IN; Fiber Optics; Human; Intubation, Intratracheal/*MT; Respiration/*; Respiration, Artificial/MT. .T Airway management in C-spine injuries [letter; comment] .P COMMENT; LETTER. .A Yealy DM; Cantees KK; McGuinness JP. .I 274653 .U 91004563 .S Can J Anaesth 9101; 37(6):709 .M Anesthesia/*AE; Canada; Coroners and Medical Examiners; Embolism, Air/*MO; Human; Registries/*. .T Fatal embolism [letter; comment] .P COMMENT; LETTER. .A Davies JM; Armstrong JN. .I 274654 .U 91004564 .S Can J Anaesth 9101; 37(6):709-10 .M Anesthesia, Epidural/*IS; Catheterization/IS; Equipment Failure; Human; Sodium Chloride/AD; Thrombosis/*PC. .T Prevention of obstruction of epidural catheter by blood clot [letter; comment] .P COMMENT; LETTER. .A Kumar CM. .I 274655 .U 91004565 .S Can J Anaesth 9101; 37(6):710-1 .M Adult; Aged; Analgesia, Epidural/*; Anesthesia, Epidural/AE; Anesthesia, Spinal/AE; Headache/*DT/ET; Human; Middle Age; Morphine/*AD/AE; Spinal Puncture/AE. .T Epidural morphine injections for the treatment of postspinal headache [letter] .P LETTER. .A Eldor J; Guedj P; Cotev S. .I 274656 .U 91004566 .S Can J Anaesth 9101; 37(6):711 .M Electromyography/DE; Hand; Human; Muscle Contraction/DE; Muscles/*DE/PH; Vecuronium/*PD. .T Clinical, electrical and mechanical correlations during recovery from neuromuscular blockade with vecuronium [letter; comment] .P COMMENT; LETTER. .A Kopman AF. .I 274657 .U 91004567 .S Can J Anaesth 9101; 37(6):712 .M Adult; Anesthesia, Epidural/*/MT; Anesthesia, Obstetrical/*; Bupivacaine/AD; Case Report; Female; Fentanyl/AD; Human; Lumbar Vertebrae/*SU; Orthopedic Fixation Devices/*; Pregnancy; Pregnancy Complications/*; Scoliosis/*SU. .T Subdural catheterization and opiate administration in a patient with Harrington rods [letter; comment] .P COMMENT; LETTER. .A Howard R; Anderson W. .I 274658 .U 91004662 .S Circ Res 9101; 67(4):1007-16 .M Adenine/PD; Adenosine Cyclic Monophosphate/PD; Adenosine Triphosphate/*PD; Animal; Calcium Channels/DE/PH; Electric Conductivity; Female; Isoproterenol/PD; Male; Membrane Potentials/PH; Myocardial Contraction/*DE; Papillary Muscles/PH; Pertussis Toxins/PD; Rats; Rats, Inbred Strains; Stimulation, Chemical; 1-Methyl-3-Isobutylxanthine/PD. .T The mechanism of positive inotropy induced by adenosine triphosphate in rat heart. .P JOURNAL ARTICLE. .W When applied extracellularly in the micromolar range, ATP and related compounds induced a positive inotropy in the rat papillary muscle. This was also true in the rat auricle after pertussis toxin treatment. Then, in both tissues, ATP further increased the contraction after a maximal beta-adrenergic stimulation. The increase in contractile force could be related to the increase in the calcium current. The L-type calcium current was measured by whole-cell patch-clamp recording in single cells isolated from the rat ventricle after the sodium and potassium currents were inhibited by tetrodotoxin and cesium, respectively. When added alone, 10 microM ATP increased the calcium current by 60%. Adenosine 5'-O-(3-thiotriphosphate) was also able to increase calcium current. Adenosine was much less effective, and GTP, UTP, CTP, and ITP were without effect. A similar increase in calcium current was observed when ATP was added in addition to a maximal stimulation by a beta-adrenergic agonist or after internal perfusion with cyclic AMP. However, this increase was preceded by a transient decrease whose origin could not be attributed to a P1-purinergic agonistic effect of ATP. The transient decrease was not elicited by adenosine or in a magnesium-free HEPES solution and was not suppressed after pertussis toxin treatment. This effect appeared related to the variations in the holding current also observed upon ATP application. Together with vasodilation, ATP and adenine compounds induced positive inotropy. The latter effect could be attributed in part to the increase in calcium current and was independent of cyclic AMP. Both effects are complementary with the beta-adrenergic stimulation and can help healthy cells to compensate the failing zone from which ATP could be released. .A Scamps F; Legssyer A; Mayoux E; Vassort G. .I 274659 .U 91004663 .S Circ Res 9101; 67(4):1017-26 .M Animal; Argipressin/AA/PD; Arterioles/DE/*PH; Colon/BS; Guinea Pigs; Human; Ileum/BS; Intestinal Mucosa/*BS; Norepinephrine/PD; Phenylephrine/PD; Rabbits; Receptors, Angiotensin/DE/PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Vascular Resistance; Vasoconstriction/DE; Vasopressins/AI/*PD. .T Characterization of vasopressin actions in isolated submucosal arterioles of the intestinal microcirculation. .P JOURNAL ARTICLE. .W Submucosal arterioles are the final resistance vessels of the mesenteric circulation; they supply intestinal mucosa and smooth muscle and contribute significantly to total mesenteric resistance. Characterization of receptors present on submucosal arterioles has not been carried out, because these vessels have not been accessible to study by previous methods. We have used a novel optical method for on-line tracking of outside diameter from in vitro preparations of submucosal arterioles in the ileum and colon of guinea pigs, rabbits, and humans to characterize the vasoconstrictor responses to vasopressin as well as other vasopressor agents along the gastrointestinal tract. All ileal submucosal arterioles showed smoothly graded constrictor responses, whereas colonic arterioles from each species exhibited rhythmic vasoconstrictions. Vasopressin constricted guinea pig and human submucosal arterioles (EC50, 1 nM) by activating classical V1 receptors; dissociation equilibrium constants (Kd) for the V1 antagonist d(CH2)5 Tyr (Me) arginine vasopressin were 1-3 nM. This antagonist was 10-50-fold more potent in inhibiting vasopressin constrictions in rabbit submucosal arterioles (Kd = 0.05-0.1 nM). No evidence for the presence of V2 receptors was obtained in any arteriole, and no significant differences in the alpha 1-adrenoceptor-mediated constrictions were observed in these vessels. Results from this study suggest the presence of heterogeneity of V1 receptors in submucosal arterioles; these differences appear to be species dependent. Our results also suggest that intrinsic vasoconstrictor properties of submucosal arterioles differ along the length of the gastrointestinal tract; these differences appear to be species independent. .A Vanner S; Jiang MM; Brooks VL; Surprenant A. .I 274660 .U 91004664 .S Circ Res 9101; 67(4):1027-34 .M Anesthesia; Animal; Aorta, Thoracic/*PA; Atherosclerosis/*PA/PP; Blood Pressure/DE; Cell Survival; Chloralose/PD; Endothelium, Vascular/IM/*PA; Heart Rate/DE; IgG/AN; Male; Metoprolol/PD; Norepinephrine/BL; Rabbits; Receptors, Adrenergic, Beta/*PH; Sympathetic Nervous System/*PP. .T Experimental sympathetic activation causes endothelial injury in the rabbit thoracic aorta via beta 1-adrenoceptor activation. .P JOURNAL ARTICLE. .W Sympathetic activation appears to accelerate the development of atherosclerosis, an effect that may be inhibited by beta-receptor blockade. It is unclear, however, which mechanisms mediate this effect. In view of the significance attached to endothelial injury in the initial phases of atherogenesis, we decided to test whether sympathetic activation might lead to an increase in endothelial injury. Chloralose anesthesia was used to induce sympathetic activation and the presence of intracellular IgG as a criterion of endothelial cell injury. The beta 1-selective beta-blocker metoprolol was used to evaluate if the effect(s) of sympathetic activation might be mediated by beta 1-adrenoceptors. In normal rabbits, the frequency of injured endothelial cells in unbranched areas of the thoracic aorta was 0.23%, compared with 1.93% in circumostial areas. Chloralose anesthesia caused significant increases in blood pressure, heart rate, and plasma norepinephrine, that is, caused sympathetic activation, and led to an approximately fivefold increase in the number of injured cells both in unbranched and in circumostial areas. This increase was totally inhibited by metoprolol pretreatment, indicating that it was mediated by beta 1-receptors. These observations suggest one possible mechanism that may connect sympathetic activation with atherogenesis and explain why beta-blockade protects against atherosclerosis. .A Pettersson K; Bejne B; Bjork H; Strawn WB; Bondjers G. .I 274661 .U 91004667 .S Circ Res 9101; 67(4):787-94 .M Actins/GE; Animal; Aorta, Abdominal; Basement Membrane/*ME; Collagen/*GE; Constriction; DNA Probes; Fibroblasts/ME; Fluorescent Antibody Technique; Gene Expression/*; Heart Enlargement/ET/*ME; Hypertension/CO; Male; Myocardium/*ME; Myofibrils/*ME; Nucleic Acid Hybridization; Rats; Rats, Inbred Strains; RNA, Messenger/ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Regulation of fibrillar collagen types I and III and basement membrane type IV collagen gene expression in pressure overloaded rat myocardium. .P JOURNAL ARTICLE. .W Left ventricular hypertrophy is based on cardiac myocyte growth. The hypertrophic process can be considered heterogeneous based on whether it also includes a remodeling and accumulation of fibrillar types I and III collagens that are responsible for impaired myocardial stiffness. In the heart, the messenger RNA (mRNA) for fibrillar collagen types I and III has been detected only in cardiac fibroblasts, whereas mRNA for basement membrane collagen type IV is present in both fibroblasts and myocytes. We studied the early and long-term expression of these collagenous proteins in rat myocardium after abdominal aortic banding with renal ischemia. Complementary DNA probes for rat pro-alpha 2 (I), mouse type III and mouse type IV collagens, and chicken beta-actin were used. Northern and dot blot analysis on total RNA extracted from left ventricular tissue indicated a sixfold increase in steady-state levels of mRNA for collagen type I on day 3 of abdominal aortic banding, which had declined to control levels by day 7 where it remained rather constant at 4 and 8 weeks. Type III collagen showed a similar pattern of gene expression after banding. mRNA levels for type IV collagen, on the other hand, were elevated on day 1 after banding, returning to control at day 7 and remaining constant. Actin mRNA levels also increased on day 1 of banding, followed by a rapid return to control levels. Monospecific antibody to types I and III collagens and immunofluorescent light microscopy on frozen sections of the myocardium revealed that at 1 week after banding, the distribution and density of these collagens were similar to those of control animals.(ABSTRACT TRUNCATED AT 250 WORDS) .A Chapman D; Weber KT; Eghbali M. .I 274662 .U 91004668 .S Circ Res 9101; 67(4):795-802 .M Animal; Antibodies, Monoclonal/*PD; Antigens, CD/IM; Capillaries/PP; Capillary Permeability; Endothelium, Vascular/PP; Female; Guinea Pigs; Human; Integrins/*IM; Lung/BS/PA; Male; Neutrophils/*PH; Opsonins/PD; Organ Weight; Phagocytosis/*; Pulmonary Edema/*ET/PA/PP; Receptors, Leukocyte-Adhesion/*IM; Support, U.S. Gov't, P.H.S.; Vasoconstriction; Zymosan/PD. .T Pulmonary edema induced by phagocytosing neutrophils. Protective effect of monoclonal antibody against phagocyte CD18 integrin. .P JOURNAL ARTICLE. .W We studied the changes in pulmonary hemodynamics and lung wet weight induced with opsonized zymosan (OZ) in isolated guinea pig lungs perfused with Ringer-albumin solution containing neutrophils (PMNs). Addition of OZ to the PMN-perfused lungs caused pulmonary vasoconstriction and weight gain; neither OZ nor PMNs added individually to the perfusate altered pulmonary vasomotor tone or wet weight. The steady gain in lung weight by 1,588 +/- 464 mg over the 45-minute study period was associated with pulmonary capillary hypertension and an increase in the capillary filtration coefficient, indicative of increased lung vascular permeability. These responses may not be due to generation of oxygen radicals, because the alterations in pulmonary hemodynamics and lung weight were not reduced by addition of superoxide dismutase, catalase, or superoxide dismutase plus catalase. We examined the basis of the PMN-mediated effects by layering PMNs on bovine pulmonary artery endothelial monolayers. Challenge with OZ resulted in increased endothelial permeability to 125I-albumin. The monoclonal antibody IB4 (directed against CD18, the common beta-subunit of structurally related adhesion receptors on phagocytes, LFA-1, Mac-1, and P150,95) prevented the OZ-mediated increase in PMN adherence to endothelial cells and the increase in endothelial permeability to 125I-albumin. IB4 also inhibited the lung weight gain mediated by the OZ-stimulated PMNs in intact lungs. The protective effect of IB4 could be ascribed neither to inhibition of uptake of OZ by PMNs nor to inhibition of release of oxygen radicals, myeloperoxidase, and elastase.(ABSTRACT TRUNCATED AT 250 WORDS) .A Kaslovsky RA; Horgan MJ; Lum H; McCandless BK; Gilboa N; Wright SD; Malik AB. .I 274663 .U 91004670 .S Circ Res 9101; 67(4):814-25 .M Acid-Base Equilibrium/*; Adenosine Triphosphate/ME; Aged; Amiloride/*AA/PD; Ammonium Chloride/PD; Bicarbonates/*PD; Buffers; Cells, Cultured; Energy Metabolism; Fluoresceins; Fluorescent Dyes; Human; Hydrogen-Ion Concentration; Mammary Arteries; Middle Age; Muscle, Smooth, Vascular/DE/*ME; Protons/*; Sodium/*ME/PD; Sodium Radioisotopes; Support, Non-U.S. Gov't; SITS/PD. .T Intracellular pH in human arterial smooth muscle. Regulation by Na+/H+ exchange and a novel 5-(N-ethyl-N-isopropyl)amiloride-sensitive Na(+)- and HCO3(-)-dependent mechanism. .P JOURNAL ARTICLE. .W We investigated in a physiological salt solution (PSS) containing HCO3- the intracellular pH (pHi) regulating mechanisms in smooth muscle cells cultured from human internal mammary arteries, using the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) and 22Na+ influx rates. The recovery of pHi from an equivalent intracellular acidosis was more rapid when the cells were incubated in CO2/HCO3(-)-buffered PSS than in HEPES-buffered PSS. Recovery of pHi was dependent on extracellular Na+ (Km, 13.1 mM); however, it was not attenuated by 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS), indicating the absence of SITS-sensitive HCO3(-)-dependent mechanisms. Recovery instead appeared mostly dependent on processes sensitive to 5-(N-ethyl-N-isopropyl)amiloride (EIPA), indicating the involvement of Na+/H+ exchange and a previously undescribed EIPA-sensitive Na(+)- and HCO3(-)-dependent mechanism. Differentiation between this HCO3(-)-dependent mechanism and Na+/H+ exchange was achieved after depletion of cellular ATP. Under these conditions, the NH4Cl-induced 22Na+ influx rate stimulated by intracellular acidosis was markedly attenuated in HEPES-buffered PSS but not in CO2/HCO3(-)-buffered PSS. EIPA also appeared to inhibit the two mechanisms differentially. In HEPES-buffered PSS containing 20 mM Na+, the EIPA inhibition curve for the intracellular acidosis-induced 22Na+ influx was monophasic (IC50, 39 nM), whereas in an identical CO2/HCO3(-)-buffered PSS, the inhibition curve exhibited biphasic characteristics (IC50, 37.3 nM and 312 microM). Taken together, the results indicate that Na+/H+ exchange and a previously undescribed EIPA-sensitive Na(+)- and HCO3(-)-dependent mechanism play an important role in regulating the pHi of human vascular smooth muscle. The involvement of the latter mechanism depends on the severity of the intracellular acidosis, varying from approximately 25% in severe intracellular acidosis up to 50% at lesser, more physiological, levels of induced acidosis. .A Neylon CB; Little PJ; Cragoe EJ Jr; Bobik A. .I 274664 .U 91004671 .S Circ Res 9101; 67(4):826-34 .M Animal; Arterioles/AH/PH; Blood Flow Velocity; Blood Viscosity; Hematocrit; Male; Microcirculation/AH/*PH; Models, Biological/*; Rats; Rats, Inbred Strains; Splanchnic Circulation/*PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Blood flow in microvascular networks. Experiments and simulation. .P JOURNAL ARTICLE. .W A theoretical model has been developed to simulate blood flow through large microcirculatory networks. The model takes into account the dependence of apparent viscosity of blood on vessel diameter and hematocrit (the Fahraeus-Lindqvist effect), the reduction of intravascular hematocrit relative to the inflow hematocrit of a vessel (the Fahraeus effect), and the disproportionate distribution of red blood cells and plasma at arteriolar bifurcations (phase separation). The model was used to simulate flow in three microvascular networks in the rat mesentery with 436,583, and 913 vessel segments, respectively, using experimental data (length, diameter, and topological organization) obtained from the same networks. Measurements of hematocrit and flow direction in all vessel segments of these networks tested the validity of model results. These tests demonstrate that the prediction of parameters for individual vessel segments in large networks exhibits a high degree of uncertainty; for example, the squared coefficient of correlation between predicted and measured hematocrit of single vessel segments ranges only between 0.15 and 0.33. In contrast, the simulation of integrated characteristics of the network hemodynamics, such as the mean segment hematocrit or the distribution of blood flow velocities, is very precise. In addition, the following conclusions were derived from the comparison of predicted and measured values: 1) The low capillary hematocrits found in mesenteric microcirculatory networks as well as their heterogeneity can be explained on the basis of the Fahraeus effect and phase-separation phenomena. 2) The apparent viscosity of blood in vessels of the investigated tissue with diameters less than 15 microns is substantially higher than expected compared with measurements in glass tubes with the same diameter. .A Pries AR; Secomb TW; Gaehtgens P; Gross JF. .I 274665 .U 91004673 .S Circ Res 9101; 67(4):844-51 .M Acetylcholine/*SE; Animal; Dogs; Electric Stimulation; Electrophysiology; Female; Heart Rate/*PH; Male; Sinoatrial Node/PH; Support, U.S. Gov't, P.H.S.; Time Factors; Vagus Nerve/*PH. .T Effects of the spatial dispersion of acetylcholine release on the chronotropic responses to vagal stimulation in dogs. .P JOURNAL ARTICLE. .W We determined the effects of changing the spatial dispersion of acetylcholine release on the phase-dependent chronotropic responses to vagal stimulation in anesthetized dogs. We stimulated the vagus nerves with one brief burst of electrical pulses each cardiac cycle, and we changed the timing of the stimulus by a small, constant amount each cardiac cycle to scan the entire cycle. To vary the heterogeneity of acetylcholine release, we changed the voltage of the stimulus pulses over a range of submaximal values. To achieve the maximum homogeneity of acetylcholine release, we used supramaximal voltages, and we varied the level of acetylcholine release from each excited fiber by changing the number of pulses per burst. We used the average cardiac cycle length of the phase-response curve to assess the overall vagal effect, independent of its timing within the cardiac cycle. We found that the amplitude of the phase-response curve varied directly and the minimum-to-maximum phase difference varied inversely with the overall efficacy of vagal activity. However, for any given alteration in the overall efficacy, the specific changes in the characteristics of the phase-response curve did not depend on whether the alteration was achieved by varying the number of pulses per burst or by varying the stimulus voltage. Therefore, we conclude that although the cardiac chronotropic response is very sensitive to changes in the timing of vagal stimulation, it is not influenced appreciably by the spatial dispersion of acetylcholine release from the vagal nerve endings over a wide range of stimulation strengths. .A Yang TE; Cheng J; Levy MN. .I 274666 .U 91004674 .S Circ Res 9101; 67(4):852-61 .M Animal; Blood Pressure/DE; Body Fluids/*PH; Capillary Permeability/DE; Dextrans/*PD; Hemodynamics/*DE; Kinetics; Lung/BS/*PH; Lymph/PH; Osmotic Pressure; Plasma Volume/DE; Proteins/*ME; Serum Albumin/ME; Sheep; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Effects of dextran 70 on hemodynamics and lung liquid and protein exchange in awake sheep. .P JOURNAL ARTICLE. .W We studied the effect of intravenous dextran 70 infusion on lung liquid and protein exchange to determine whether its effects were due to altered hemodynamics or to altered microvascular permeability. In each of six instrumented awake sheep with chronic lung lymph fistulas, we performed three experiments: 1) control, 2) a 30-minute infusion of 1 l of 6% dextran 70, and 3) an infusion of 1 l of 0.9% NaCl. In addition to pulmonary hemodynamics and lymph dynamics, we measured the plasma-to-lung lymph equilibration rate of [125I] albumin. We followed all the sheep for 10 hours, including a 2-hour baseline period. Dextran was more effective in expanding plasma volume (63 +/- 15% [mean +/- SD]) than saline (11 +/- 6%) at the end of the 30-minute infusion. Pulmonary vascular pressures increased after dextran and remained elevated for 8 hours, whereas after saline the pressures returned to baseline within 1 hour. After dextran, lung lymph flow increased and remained elevated. It was only transiently increased after saline. We confirmed that dextran equilibrated rapidly with lung lymph (half-time, less than 0.6 hour), even though it maintained plasma volume expansion for the whole body (half-time, 11.1 +/- 2.7 hours). The dextran increased both plasma and lymph total macromolecular osmotic pressure but did not increase the plasma-interstitial (lymph) osmotic pressure difference in the lung, except transiently during the infusion. The lymph/plasma protein concentration ratio increased after dextran due mainly to plasma protein dilution. There were no differences in the half-time of tracer albumin equilibration between plasma and lung lymph (control, 2.2 +/- 0.6 hours; saline, 2.0 +/- 0.6 hours; dextran, 2.3 +/- 0.6 hours). Dextran 70 increased liquid filtration mainly by increasing microvascular pressure and possibly filtration surface area. There was no evidence for a change in the leakiness of the lung microvascular barrier to albumin. .A Arakawa M; Jerome EH; Enzan K; Grady M; Staub NC. .I 274667 .U 91004675 .S Circ Res 9101; 67(4):862-70 .M Adrenergic Beta Receptor Blockaders/PD; Animal; Blood Pressure/DE; Cats; Electric Stimulation; Female; Lung/*BS/IR; Male; Norepinephrine/*PH; Prazosin/PD; Propanolamines/PD; Propranolol/PD; Receptors, Adrenergic, Alpha/*PH; Receptors, Adrenergic, Beta/*PH; Support, U.S. Gov't, P.H.S.; Sympathetic Nervous System/*PH; Yohimbine/PD. .T Analysis of pulmonary vascular responses in cats to sympathetic nerve stimulation under elevated tone conditions. Evidence that neuronally released norepinephrine acts on alpha 1-, alpha 2-, and beta 2-adrenoceptors. .P JOURNAL ARTICLE. .W The influence of an increase in vascular tone on responses to sympathetic nerve stimulation and the receptors mediating these responses were investigated in the pulmonary vascular bed of the cat. Under conditions of controlled blood flow and constant left atrial pressure, stimulation of the sympathetic nerves to the lung elicited a biphasic response characterized by an initial increase in lobar arterial pressure followed closely by a decrease. The response to nerve stimulation was reproducible with respect to time and was not altered when a delay coil was added to the perfusion circuit, indicating that the response was directly mediated. The increase in pressure was reduced by prazosin and by yohimbine, whereas the decrease in pressure was blocked by propranolol or ICI 118551. These data suggest that the pressor component of the response is mediated by alpha 1- and postjunctional alpha 2-adrenoceptors, whereas the depressor response is mediated by beta 2-receptors. The pressor response was enhanced by propranolol or ICI 118551, whereas the depressor response was enhanced by prazosin or yohimbine, suggesting that the response to nerve stimulation represents the net effect of the actions of neuronally released norepinephrine on alpha- and beta-receptors. The pressor response to nerve stimulation was enhanced when tone was elevated with a prostaglandin endoperoxide analogue and when beta-receptors were blocked. The effects of an increase in tone and a passive increase in pressure on responses to sympathetic nerve stimulation were different.(ABSTRACT TRUNCATED AT 250 WORDS) .A Hyman AL; Lippton HL; Kadowitz PJ. .I 274668 .U 91004676 .S Circ Res 9101; 67(4):871-85 .M Aging/*PH; Animal; Blood Pressure; Cell Count; Heart/PP; Heart Enlargement/*PA/PP; Heart Rate; Heart Ventricle/PP; Hyperplasia; Male; Myocardium/*PA; Organ Weight; Rats; Rats, Inbred F344; Support, U.S. Gov't, P.H.S.. .T Myocyte cell loss and myocyte cellular hyperplasia in the hypertrophied aging rat heart. .P JOURNAL ARTICLE. .W To determine the effects of age on the myocardium, the functional and structural characteristics of the heart were studied in rats at 4, 12, 20, and 29 months of age. Mean arterial pressure, left ventricular pressure and its first derivative (dP/dt), and heart rate were comparable in rat groups up to 20 months. During the interval from 20 to 29 months, elevated left ventricular end-diastolic pressure and decreased dP/dt indicated that a significant impairment of ventricular function occurred with senescence. In the period between 4 and 12 months, a reduction of nearly 19% in the total number of myocytes was measured in both ventricles. In the subsequent ages, similar decreases in myocyte cell number were found in the left ventricle, whereas in the right ventricle, the initial loss was fully reversed by 20 months. Moreover, from 20 to 29 months, a 59% increase in the aggregate number of myocytes occurred in the right ventricular myocardium. In the left ventricle, a 3% increment was also seen, but this small change was not statistically significant. These estimations of myocyte cellular hyperplasia, however, were complicated by the fact that cell loss continued to take place with age. The volume fraction of collagen in the tissue, in fact, progressively increased from 8% and 7% at 4 months to 16% and 22% at 29 months in the left and right ventricles, respectively. In conclusion, myocyte cellular hyperplasia tends to regenerate the ventricular mass being lost with age in the adult mammalian rat heart. .A Anversa P; Palackal T; Sonnenblick EH; Olivetti G; Meggs LG; Capasso JM. .I 274669 .U 91004677 .S Circ Res 9101; 67(4):886-92 .M Animal; Dogs; Electrocardiography; Mathematics/*; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Ventricular Fibrillation/PP. .T Is fibrillation chaos? .P JOURNAL ARTICLE. .W Ventricular fibrillation is examined to determine whether it is an instance of deterministic chaos. Surface ECGs from dogs in fibrillation were used to generate a state space representation of fibrillation. Our analysis failed to identify a low-dimensional attractor that could be associated with fibrillation. The results suggest that fibrillation is similar to a nonchaotic random signal. We note, however, that such random-looking but nonchaotic behavior can also be generated by a nonlinear deterministic system. .A Kaplan DT; Cohen RJ. .I 274670 .U 91004678 .S Circ Res 9101; 67(4):893-901 .M Animal; Biomechanics; Calcium/PD; Elasticity; Energy Metabolism/*; Mathematics; Myocardial Contraction/DE/*PH; Papillary Muscles/AH/DE/*PH; Pressure; Rabbits. .T Heat released during relaxation equals force-length area in isometric contractions of rabbit papillary muscle. .P JOURNAL ARTICLE. .W It has been claimed that the mechanical performance and the related energy turnover of the left ventricle can be reliably predicted on the basis of its time-varying elastance behavior. In its most elementary form, this behavior can be mathematically described by E(t) = P(t)/[V(t)-Vd], where E is ventricular elastance, t is time, P is ventricular pressure, V is ventricular volume, and Vd is the intercept of the end-systolic pressure-volume line on the volume axis. To find out how this behavior of the ventricle as a whole is related to the properties of the myocardium, we tested the energetic prediction for the ventricle that the pressure-volume area of an isovolumic contraction equals the energy released in relaxation in experiments on isolated rabbit papillary muscle at 20 degrees C. To that end, the energy (joules) contained by the force-length area of the muscles, contracting isometrically, was compared with the heat (joules) liberated in relaxation as measured with thermopiles. Mechanical performance of the muscles was varied by altering initial muscle length and external calcium. The slope of the resulting relation between force-length area and heat liberated in relaxation (n = 26) was not significantly different from unity. Thus, the energetic prediction of the time-varying elastance model developed for the whole left ventricle was confirmed by experiments on rabbit papillary muscle at 20 degrees C. .A Mast F; Elzinga G. .I 274671 .U 91004679 .S Circ Res 9101; 67(4):902-12 .M Animal; Carbon Radioisotopes; Chromatography, High Pressure Liquid; Comparative Study; Dogs; Female; Indicator Dilution Techniques/*; Kinetics; Leucine/ME; Male; Muscles/ME; Myocardium/*ME; Phenylalanine/ME; Proteins/BI/*ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tritium. .T In vivo measurement of myocardial protein turnover using an indicator dilution technique. .P JOURNAL ARTICLE. .W We applied a nondestructive tracer technique, previously developed for measuring skeletal muscle protein turnover, to the measurement of myocardial protein turnover in vivo. During a continuous infusion of L-[ring-2,6-3H]phenylalanine to anesthetized, overnight-fasted dogs, we measured the uptake of radiolabeled phenylalanine from plasma and the release of unlabeled phenylalanine from myocardial proteolysis using arterial and coronary sinus catheterization and analytic methods previously applied to skeletal muscle. Using these measurements, together with a model of myocardial protein synthesis that assumes rapid equilibration of tracer specific activity between myocardial phenylalanyl-tRNA and circulating phenylalanine, we estimated the rates of heart protein synthesis and degradation. The rate of heart protein synthesis was also estimated directly from the incorporation of labeled phenylalanine into tissue protein. The use of [3H]phenylalanine was compared with L-[1-14C]leucine in the measurement of heart protein turnover in dogs given simultaneous infusion of both tracers. Leucine uptake and release by the myocardium exceeded that of phenylalanine by 3.1 +/- 0.4- and 1.7 +/- 0.3-fold, respectively, consistent with leucine's 2.4-fold greater abundance in heart protein and its metabolism via other pathways. Phenylalanine is the preferred tracer for use with this method because of its limited metabolic fate in muscle. One theoretical limitation to the method, slow equilibration of circulating labeled phenylalanine with myocardial phenylalanyl-tRNA, was resolved by comparison of these specific activities after a 30-minute infusion of labeled phenylalanine in the rat. A second, empirical limitation involves precision in the measurement of the small decrements in phenylalanine specific activity that occur with each pass of blood through the coronary circulation. This was addressed by improving the precision of both the measurements of phenylalanine concentration and phenylalanine specific activity using high-performance liquid chromatography. We conclude that the in vivo measurement of phenylalanine tracer exchange across the myocardium permits the nondestructive estimation of heart protein turnover in the intact animal. .A Revkin JH; Young LH; Stirewalt WS; Dahl DM; Gelfand RA; Zaret BL; Barrett EJ. .I 274672 .U 91004680 .S Circ Res 9101; 67(4):913-22 .M Action Potentials; Animal; Caffeine/PD; Calcium/AD/PD; Electric Stimulation; Isoproterenol/PD; Myocardial Contraction/DE/*PH; Potassium/AD/PD; Rats; Ryanodine/PD; Sarcolemma/*PH; Sarcomeres/*PH/UL; Sarcoplasmic Reticulum/*PH; Sodium/AD/PD; Strontium/PD; Support, Non-U.S. Gov't; Tetraethylammonium Compounds/PD. .T Sarcolemma, sarcoplasmic reticulum, and sarcomeres as limiting factors in force production in rat heart. .P JOURNAL ARTICLE. .W Inotropic interventions were compared with respect to their maximum effect on force of contraction in rat myocardium to identify limiting steps in calcium handling. Peak force, sarcomere length, and action potentials were measured in thin ventricular trabeculae. Relevant control conditions were stimulation frequency, 0.2 Hz; [Ca2+]o, 1 mM; [K+]o, 5 mM; [Na+]o, 150 mM. The inotropic interventions and results were as follows. 1) The interventions of high [Ca2+]o, low [Na+]o, high [K+]o, addition of tetraethylammonium chloride, or postextrasystolic potentiation resulted in approximately the same (within 5%) maximum force (Fmax). Above the respective optimum doses, force declined and aftercontractions were often observed. Combinations of the different interventions never enhanced force to above Fmax. This suggests that Fmax is determined by a maximum level of Ca2+ in the sarcoplasmic reticulum, above which spontaneous release occurs. 2) Sr2+ (10 mM) caused an increase of force to 1.3 X Fmax and lengthening of contraction and action potentials. The force-sarcomere length relation was, then, similar to that in skinned fibers at maximum activation. Hence, 1.3 X Fmax reflects saturation of the sarcomeres. We postulate that a large influx of Sr2+ during the long action potential can circumvent the reticulum and activate the sarcomeres directly. When the reticulum was blocked with ryanodine, maximum force of tetanic contractions was about 1.1 X Fmax. This result supports the above conclusions. 3) Isoproterenol increased force to a maximum that was 20% below Fmax and shortened the contraction. This may be due to a decreased sensitivity of the sarcomeres to Ca2+ or to stimulation of the Ca2+ pump in the reticulum, that is, an increasing fraction of the released Ca2+ is sequestered before it can activate the sarcomeres. Thus, three factors that limit force production were identified, depending on the inotropic stimulus. .A Schouten VJ; Bucx JJ; de Tombe PP; ter Keurs HE. .I 274673 .U 91004681 .S Circ Res 9101; 67(4):923-32 .M Animal; Blood Pressure; Coronary Vessels/*PH; Diastole/*PH; Dogs; Heart/*PH; Heart Atrium/PH; Heart Rate; Heart Ventricle/AH/PH; Pressure; Support, U.S. Gov't, P.H.S.; Venous Pressure/*PH. .T Effects of coronary venous pressure on left ventricular diastolic distensibility. .P JOURNAL ARTICLE. .W Coronary arterial pressure and flow are known to influence left ventricular (LV) diastolic distensibility, but the influence of coronary venous pressure is unknown. To test the hypothesis that increased coronary venous pressure leads to an increase in LV wall volume and a decrease in LV diastolic distensibility, we studied excised, blood-perfused LV isovolumic dog hearts without the pericardium. In protocol I (n = 8), to raise coronary venous pressure the pressure of right atrium (RA) and right ventricle (RV) was increased by the height of a blood reservoir connected with a cannula that opened in both the RA and RV. In protocol II (n = 7), to isolate the effect of RV enlargement on LV diastolic distensibility (direct ventricular interaction), an isovolumic RV balloon was used with coronary venous pressure held constant at 0 mm Hg. Changes in LV diastolic distensibility were assessed by shifts of the LV end-diastolic pressure-volume relation. Changes in LV wall volume were detected by subepicardial segment length at end-diastole. The mean pressures of RA and RV (protocol I) and RV balloon only (protocol II) were increased from 0 to 15 and 30 mm Hg over a range of LV volume. In protocol I, when RA.RV pressure was increased from 0 to 30 mm Hg at three levels of LV volume (22 +/- 2, 31 +/- 3, and 40 +/- 3 ml), LV end-diastolic pressures increased significantly from 5.2 +/- 0.3 to 11.2 +/- 1.5, from 10.4 +/- 0.3 to 18.2 +/- 1.2, and from 20.2 +/- 1.0 to 28.8 +/- 1.2 mm Hg, respectively. In protocol II, when RV balloon pressure was increased from 0 to 30 mm Hg at the three LV volumes (21 +/- 3, 31 +/- 3, and 41 +/- 4 ml), LV end-diastolic pressures showed smaller increases from 5.2 +/- 0.2 to 6.6 +/- 0.2, from 9.8 +/- 0.3 to 11.6 +/- 0.6, and from 19.0 +/- 0.5 to 21.4 +/- 0.8 mm Hg, respectively. In both protocols, the LV end-diastolic pressure-volume relation shifted upward in a nearly parallel fashion, but the shift was much greater in protocol I than in protocol II. Despite constant LV volume, an increase in LV wall dimension in protocol I was significant and much greater than that in protocol II. From these results, we conclude that increased coronary venous pressure decreases LV diastolic distensibility with increasing LV wall volume, and this mechanism appears to act independently of diastolic ventricular interaction caused by RV enlargement. .A Watanabe J; Levine MJ; Bellotto F; Johnson RG; Grossman W. .I 274674 .U 91004682 .S Circ Res 9101; 67(4):933-40 .M Amino Acid Sequence; Animal; Base Sequence; Chickens; Cloning, Molecular/*; Comparative Study; Dihydropyridines/*PD; DNA/*GE; Gene Expression; Gizzard/CH; Molecular Sequence Data; Myosin-Light-Chain Kinase/*GE; Nucleic Acid Hybridization; Phosphorylation; Restriction Mapping; RNA, Messenger/AN; Sequence Homology, Nucleic Acid; Species Specificity; Tissue Distribution. .T Cloning and characterization of a vertebrate cellular myosin regulatory light chain complementary DNA. .P JOURNAL ARTICLE. .W We have isolated two series of complementary DNAs (cDNAs) from a chicken gizzard cDNA library encoding two isoforms of phosphorylatable myosin regulatory light chain (RLC). One of the cDNAs encodes a previously isolated smooth muscle myosin RLC (also referred to as LC20-A); the other encodes a protein that shares 92% homology with the LC20-A isoform. The phosphorylatable threonine and serine residues at positions 18 and 19 of the two myosin RLC sequences are conserved. The two cDNAs are 81% homologous at the nucleotide level over the coding region; the 5' and 3' untranslated regions are divergent. Most of the DNA nonhomology in the coding region does not affect the protein sequence, indicating strong evolutionary conservation pressure to maintain the myosin RLC structure. Northern blot analysis using 3' untranslated region probes reveals restrictive tissue specific expression of one myosin RLC isoform (LC20-A) in smooth muscle tissue and not in other tissues examined. In contrast, the novel myosin RLC isoform messenger RNA (mRNA) is uniformly expressed in all smooth and nonmuscle tissues examined and is designated as cellular myosin RLC for this reason. Our results indicate that cellular and smooth muscle myosin RLC isoforms are distinct and are encoded by separate genes. This report describes the cloning of a novel vertebrate cellular myosin RLC mRNA that differs from previously characterized smooth muscle RLC isoform mRNAs in both primary sequence and expression pattern. .A Zavodny PJ; Petro ME; Lonial HK; Dailey SH; Narula SK; Leibowitz PJ; Kumar CC. .I 274675 .U 91004683 .S Circ Res 9101; 67(4):941-7 .M Adenosine Diphosphate/PD; Amino Acid Sequence; Drug Synergism; Fibrinogen/*PD; Human; Molecular Sequence Data; Oligopeptides/CS/PD; Peptide Fragments/PD; Peptides/*PD; Platelet Aggregation/DE; Platelet Aggregation Inhibitors/*PD; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.. .T Synergistic inhibition of platelet aggregation by fibrinogen-related peptides. .P JOURNAL ARTICLE. .W We have evaluated the ability of the fibrinogen-related peptides Gly-Arg-Gly-Asp-Ser (GRGDS), Gly-Gln-Gln-His-His-Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val (gamma-chain peptide), and Gly-Pro-Arg-Pro (GPRP) to inhibit platelet aggregation in platelet-rich plasma individually and in combination. When used alone, GRGDS totally inhibited ADP-induced aggregation of human platelets in platelet-rich plasma; however, the maximum inhibitory effect of the other peptides was less than 80%. The concentrations necessary to inhibit platelet aggregation in plasma by 50% were 100 mumols/l and 1 and 3.2 mmol/l for GRGDS, gamma-chain peptide, and GPRP, respectively. When evaluating the effect of peptide mixtures, we discovered that the combination GPRP + GRGDS worked together synergistically (p less than 0.001, analysis by surface response methodology), whereas GPRP + gamma-chain peptide did not. For example, our analysis indicated that a mixture of 50 mumols/l GRGDS plus 180 mumols/l GPRP would produce 50% inhibition of platelet aggregation. This is an effect twofold greater than that produced by 50 mumols/l GRGDS alone, and one that would require an 18-fold greater concentration of GPRP if used alone. These data indicate that the combination GPRP + GRGDS inhibited platelet aggregation in plasma in a synergistic fashion and suggest the potential value of their combined use in antithrombotic therapy. .A Adelman B; Gennings C; Strony J; Hanners E. .I 274676 .U 91004684 .S Circ Res 9101; 67(4):948-59 .M Adenosine Triphosphate/ME; Animal; Anoxia/*PA/PP; Aorta/SU; Constriction; Coronary Disease/*PA/PP; Glycogen/ME; Heart Enlargement/*PA/PP; Heart Ventricle/PP; Lactates/ME; Male; Microscopy, Electron; Myocardial Contraction; Myocardium/ME/PA; Phosphocreatine/ME; Pressure; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Increased ischemic injury but decreased hypoxic injury in hypertrophied rat hearts. .P JOURNAL ARTICLE. .W The purpose of this study was to compare the degree of ischemic and hypoxic injury in normal versus hypertrophied rat hearts to investigate basic mechanisms responsible for irreversible myocardial ischemic injury. Hearts from rats with bands placed on the aortic arch at 23 days of age (BAND) and sham-operated rats (SHAM, 8 weeks postoperative) were isolated, perfused with Krebs buffer, and had a left ventricular balloon to measure developed pressure. Hearts were made globally ischemic until they developed peak ischemic contracture and were reperfused for 30 minutes. Additional hearts were perfused for 15 minutes with glucose-free hypoxic buffer followed by 20 minutes of oxygenated perfusion. There was an 87% increase in heart weight of BAND compared with SHAM (p less than 0.01). During ischemia, lactate levels increased faster in BAND compared with SHAM, ischemic contracture occurred earlier in BAND than in SHAM despite no difference in ATP levels, and postischemic recovery of left ventricular pressure was less in BAND (26.8 +/- 5.6% of control left ventricular pressure, mean +/- SEM) compared with SHAM (40 +/- 4.6%, p less than 0.05). During hypoxic perfusion, lactate release was greater in BAND than in SHAM (48.8 +/- 1.2 versus 26.6 +/- 0.97 mumols/g, p less than 0.01), and with reoxygenation, lactate dehydrogenase release was less in BAND than in SHAM (13.2 +/- 0.7 versus 19.5 +/- 0.2 IU/g, p less than 0.01). After hypoxia and reoxygenation, left ventricular pressure recovery was greater in BAND than in SHAM (93 +/- 8.4% versus 66 +/- 5.3%, p less than 0.01). Thus, this study suggests that hypertrophied hearts have a greater potential for glycolytic metabolism, resulting in an increased rate of by-product accumulation during ischemia, which may be responsible for the increased susceptibility of hypertrophied hearts to ischemic injury. .A Anderson PG; Allard MF; Thomas GD; Bishop SP; Digerness SB. .I 274677 .U 91004685 .S Circ Res 9101; 67(4):960-78 .M Adenine/AA/PD; Adenosine/AD/*PD; Adenosine Deaminase/AI; Animal; Anoxia/PP; Atrioventricular Node/DE/*PP; Bundle of His/PP; Comparative Study; Depression, Chemical; Dipyridamole/PD; Female; Guinea Pigs; Heart Atrium/PP; Heart Block/PP; Heart Rate/*DE; Male; Rabbits; Rats; Rats, Inbred Strains; Species Specificity; Xanthines/PD. .T Species-dependent effects of adenosine on heart rate and atrioventricular nodal conduction. Mechanism and physiological implications. .P JOURNAL ARTICLE. .W This study 1) compares the negative chronotropic and dromotropic actions of adenosine in guinea pig, rat, and rabbit hearts; 2) investigates the mechanism(s) for the different responses; and 3) determines the physiological implications. Isolated perfused hearts were instrumented for measurement of atrial rate and atrioventricular (AV) nodal conduction time. Differences in metabolism of adenosine were determined in the absence and presence of dipyridamole (nucleoside uptake blocker) and erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA, adenosine deaminase inhibitor). Dipyridamole plus EHNA decreased adenosine's EC50 for the negative dromotropic effect by 14-fold in guinea pig heart and 1.6-fold in rat heart. This is consistent with the greater number of [3H]nitrobenzylthioinosine binding sites measured in membranes from guinea pig (1,231 +/- 68 fmol/mg protein) compared with rat (302 +/- 31 fmol/mg protein) and rabbit (260 +/- 28 fmol/mg protein) atria. The potency of adenosine to slow atrial rate and prolong AV nodal conduction time was greater in guinea pig than in rat or rabbit hearts. This rank order of potency correlated well with the number of binding sites for the specific adenosine receptor radioligand 125I-aminobenzyladenosine in guinea pig (102 +/- 13 fmol/mg protein), rat (11 +/- 0.5 fmol/mg protein), and rabbit (8 +/- 1 fmol/mg protein) atrial membranes. Hypoxia increased the rate of adenosine release by severalfold and caused slowing of heart rate and AV block. In spontaneously beating hearts, the main effect of hypoxia was a slowing of ventricular rate, which in the guinea pig heart was due to AV block and in the rat heart to atrial slowing. In atrial paced hearts, hypoxia caused a marked prolongation of AV nodal conduction time in guinea pig (39 +/- 4 msec) and rabbit (29 +/- 5 msec) hearts, but only small effect in rat hearts (10 +/- 2 msec). The differences in response to hypoxia could be accounted for by the species-dependent differences in the 1) amount of adenosine released and metabolized, 2) sensitivity of the hearts to adenosine, and 3) dependency of AV nodal conduction on atrial rate. The findings indicate that the results from physiological or pharmacological studies on adenosine in one species may not be applicable to others, and the ultimate effect of adenosine and hypoxia is to slow ventricular rate. .A Froldi G; Belardinelli L. .I 274678 .U 91004686 .S Circ Res 9101; 67(4):979-85 .M Adenosine Triphosphate/PD; Animal; Arginine/*AA/PD; Bradykinin/PD; Calcimycin/PD; Cattle; Cells, Cultured; Endothelium-Derived Relaxing Factor/*AI/PD; Endothelium, Vascular/DE/*ME; Guanosine Cyclic Monophosphate/*ME; Melitten/PD; Muscle, Smooth, Vascular/DE/*ME; Pulmonary Artery; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T NG-monomethyl L-arginine inhibits endothelium-derived relaxing factor-stimulated cyclic GMP accumulation in cocultures of endothelial and vascular smooth muscle cells by an action specific to the endothelial cell. .P JOURNAL ARTICLE. .W The effect of NG-monomethyl L-arginine (LNMMA), an analogue of L-arginine (a proposed precursor of endothelium-derived relaxing factor [EDRF]), on EDRF release from bovine pulmonary artery endothelial cells was investigated using endothelial cell-vascular smooth muscle cocultures and a superfused column containing endothelial cells grown on microcarrier beads. Cocultures were stimulated with control buffer, ATP, bradykinin, melittin, A23187, or nitroprusside in the presence and absence of varying concentrations of LNMMA (30-300 microM). LNMMA caused significant, concentration-dependent decreases in cyclic GMP accumulation in response to the endothelium-dependent dilators bradykinin, ATP, melittin, and A23187 but had no effect on control or nitroprusside-stimulated cocultures. The inhibitory effect of LNMMA on cyclic GMP accumulation was partially reversed by treatment with L-arginine, but was unaffected by D-arginine. To determine the specific site of action of LNMMA, endothelial cells on microcarrier beads were placed in a column and superfused with buffer. The effluent from the column was collected in 30-second (1.5-ml) fractions into 2-cm2 monolayer wells of vascular smooth muscle cells before and after addition of agonists (bradykinin, A23187) to the column inflow. The cyclic GMP content of each well of smooth muscle cells was determined as an index of EDRF activity. LNMMA superfused through the endothelial cell column inhibited cyclic GMP accumulation in vascular smooth muscle cells induced by bradykinin and A23187. LNMMA introduced into the effluent from the endothelial cell column had no effect on smooth muscle cyclic GMP levels. We conclude that LNMMA is an effective, specific inhibitor of EDRF production or release, and its action is specific to the endothelial cell. .A Johns RA; Peach MJ; Linden J; Tichotsky A. .I 274679 .U 91004687 .S Circ Res 9101; 67(4):986-92 .M Animal; Animals, Newborn/*PH; Blood Pressure/*DE; Cardiovascular System/DE/GD/*PH; Denervation; Dogs; Drug Synergism; Female; Heart Rate/DE; Male; Parasympathetic Nervous System/PH; Phentolamine/*PD; Propranolol/PD; Receptors, Adrenergic, Alpha/*PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Vagotomy; Vasoactive Intestinal Peptide/*PD/PH. .T Synergistic hypotensive effect of vasoactive intestinal polypeptide and alpha-blockade with phentolamine. Evidence for vasoactive intestinal peptide alpha-adrenoceptor coupling in the cardiovascular system of newborn dogs. .P JOURNAL ARTICLE. .W Vasoactive intestinal polypeptide (VIP) is a neuropeptide with potent circulatory effects in the adult animal and human. Little is known about its effects or mechanism of action in the immature animal. These series of experiments evaluated the effects and possible mechanism of action of VIP on the developing canine cardiovascular system. In all three series, measurements of mean heart rate and blood pressure were taken in the control state, after parasympathetic denervation with bilateral cervical vagotomies, and after autonomic blockade with propranolol (1 mg/kg) and phentolamine (0.5 mg i.v.). In series 1, we characterized the role of alpha-adrenergic receptors in early newborn puppies by investigating the hemodynamic effects of phentolamine alone in five early newborn puppies. In series 2, the hemodynamic effects of intravenous VIP infusion (0.2 microgram/kg/min) were recorded and compared in six early newborn puppies and in 10 late newborn puppies. In series 3, the hemodynamic effects of phentolamine in the presence of VIP receptor binding inhibitor were studied. In early newborn puppies, VIP had essentially no effect on heart rate or blood pressure until phentolamine was given; then, blood pressure decreased by 17% (p less than 0.005). In late newborn puppies, VIP resulted in an increase in heart rate in the control state but not after parasympathetic or sympathetic denervation. In early newborn puppies, phentolamine alone resulted in a 24% decrease (p less than 0.005) in blood pressure, compared with a 54% decrease (p less than 0.005) in early newborn puppies preexposed to VIP infusion.(ABSTRACT TRUNCATED AT 250 WORDS) .A Mas MS; Adams DJ; Gelband H. .I 274680 .U 91004688 .S Circ Res 9101; 67(4):993-1006 .M Animal; Barium/*ME; Basilar Artery/PH; Calcium Channels/DE/*PH; Dihydropyridines/*PD; Electric Conductivity; Kinetics; Male; Membrane Potentials; Muscle, Smooth, Vascular/*PH; Potassium/ME; Rabbits. .T Dual action of FRC8653, a novel dihydropyridine derivative, on the Ba2+ current recorded from the rabbit basilar artery. .P JOURNAL ARTICLE. .W Actions of FRC8653 on the macroscopic and unitary Ba2+ currents were studied using the rabbit basilar artery. Application of (+/-)-FRC8653 (less than 1 microM) increased the amplitude of the inward current when depolarization pulses more negative than -10 mV were applied but inhibited it when depolarization was more positive than 0 mV (in each case from a holding potential of -80 mV). At a holding potential of -40 mV, (+/-)-FRC8653 (greater than 0.1 nM) consistently inhibited the inward current. (-)-FRC8653 (greater than 1 nM) inhibited the amplitude of the inward current evoked by a depolarizing pulse more positive than -10 mV (the holding potential being -80 mV). At the holding potential of -80 mV, but not at -40 mV, (+)-FRC8653 (1 microM) enhanced the current amplitude evoked by a depolarizing pulse more negative than -10 mV but inhibited the current evoked by a pulse more positive than 0 mV. (+/-)-FRC8653 shifted the voltage-dependent inhibition curves to the left, and the slope of the curve became steeper (test pulse of +10 mV). Two types of single Ca2+ channel currents (12 and 23 pS) were recorded from the basilar artery by the cell-attached patch-clamp method. Opening of the 12-pS channel occurred with a depolarizing pulse (-20 mV) from a holding potential of -80 mV, but not from one of -60 mV. (+)-FRC8653 activated, and (-)-FRC8653 inhibited, the 23-pS channel.(ABSTRACT TRUNCATED AT 250 WORDS) .A Oike M; Inoue Y; Kitamura K; Kuriyama H. .I 274681 .U 91004983 .S Clin Orthop 9101; (259):1-91 .M Arthritis, Juvenile Rheumatoid/*; Child; Human. .T Symposium. Arthritis in childhood. .P OVERALL. .I 274682 .U 91004984 .S Clin Orthop 9101; (259):100-10 .M Adolescence; Adult; Bone Nails; Bone Plates; Bone Screws; Child; Epiphyses, Slipped/CO/*SU; Female; Femur Neck/*SU; Follow-Up Studies; Human; Male; Osteoarthritis/ET; Osteotomy/*MT. .T Intertrochanteric corrective osteotomy in slipped capital femoral epiphysis. A long-term follow-up study of 26 patients. .P JOURNAL ARTICLE. .W The results of intertrochanteric corrective osteotomy in a series of 26 hips with moderate to severe chronic slipped capital femoral epiphysis are reported from follow-up studies in 1976 and 1986. In hips with a slippage of less than 40 degrees (ten hips), arthrosis was present in one hip. In the remaining 16 cases in which slippage exceeded 40 degrees, osteoarthrosis was present in 15, even though correction was adequate. From these observations it can be concluded that intertrochanteric corrective osteotomy does not prevent degeneration in cases with the most severe slip. On the basis of the present observations on treated and untreated cases, the authors advocate treatment by fixation without realignment, accepting the deformity in moderate and severe chronic slips. Rotational osteotomy may be considered in the event of hip joint contracture. .A Maussen JP; Rozing PM; Obermann WR. .I 274683 .U 91004985 .S Clin Orthop 9101; (259):11-7 .M Arthritis, Juvenile Rheumatoid/*GE/IM; Child; Chromosomes, Human, Pair 6; Human; HLA Antigens/*AN. .T Genetic aspects of juvenile chronic arthritis. .P JOURNAL ARTICLE; REVIEW; REVIEW LITERATURE. .W Immunogenetic studies in the past decade have confirmed the theory of an association between one's immunogenetic background and the manifestation of several forms of juvenile chronic arthritis (JCA), in particular pauciarticular-onset JCA. Considerable work has been done at the serologic level to demonstrate disease association with the major histocompatibility Class II antigens in pauciarticular-onset JCA. The polygenic nature of JCA is best illustrated by the findings in this particularly well-defined clinical subgroup. Evidence is now emerging that analysis of the DNA sequence, the derived protein sequence, and the structure of Class II molecules will yield significant insight into the genetic predisposition to JCA. .A Woo P. .I 274684 .U 91004986 .S Clin Orthop 9101; (259):111-3 .M Bone Plates/*; Bone Screws; Femur Neck/*SU; Human; Osteotomy/*IS. .T Cannulated blade plate for proximal femoral varus osteotomy. .P JOURNAL ARTICLE. .W Fixation of the osteotomy site in the proximal femur is technically demanding. A new system, which includes cannulated chisels and a cannulated one-piece plate that can be inserted over a guide wire, is suggested. The new system simplifies the procedure and provides stable fixation. .A Grant AD; Lehman WB; Strongwater AM; Atar D. .I 274685 .U 91004987 .S Clin Orthop 9101; (259):114-21 .M Aged; Aged, 80 and over; Bone Cements; Female; Femoral Neck Fractures/ET/*SU; Follow-Up Studies; Fracture Fixation, Internal/MT; Hip Prosthesis/*/AE; Human; Male; Middle Age; Osteoarthritis/*CO/PA; Osteoporosis/*CO/PA; Postoperative Complications/*ET. .T Five-year postoperative results of cemented femoral arthroplasty in patients with systemic bone disease. .P JOURNAL ARTICLE. .W To determine whether bone cellular abnormality affects the results of cemented femoral arthroplasty, 21 patients had biopsies of the iliac crest and femoral cortex at the time of surgery. Roentgenographic and histomorphometric studies were used to characterize fibrous membrane formation, cancellous bone, calcar resorption, and bone turnover. Patients with high bone turnover and decreased femoral thickness and density before surgery were at risk of developing calcar resorption and cancellous diaphyses, conditions that weaken proximal stem support and lead to early failure. These findings suggest that noncemented stems may be indicated in this group. Another group, osteoporotic patients, suffered from osteoblastic insufficiency, which may be the indication for the use of cemented stems rather than noncemented stems, which require bony ingrowth. .A Dorr LD; Arnala I; Faugere MC; Malluche HH. .I 274686 .U 91004988 .S Clin Orthop 9101; (259):122-9 .M Acrylic Resins; Bone Cements/*; Centrifugation; Porosity. .T Porosity of various preparations of acrylic bone cements. .P JOURNAL ARTICLE. .W The total porosity and mean pore sizes of various bone cement preparations were measured using image analysis. The porosity in different commercial bone cements varied from 5% to 16% when these cements were prepared in the usual fashion. Centrifugation for 30 seconds resulted in a substantial reduction in the overall porosity of Simplex P, AKZ, Zimmer Regular, and CMW bone cements by reducing both the mean pore size and the number of pores per unit area. In contrast, the porosity of LVC, Palacos R, and Palacos R with gentamicin bone cements was not significantly decreased by centrifugation. Chilling the monomer before mixing resulted in higher porosity of both the centrifuged and uncentrifuged Simplex P, Zimmer Regular, and CMW bone cements. Simplex P mixed with chilled monomer and centrifuged for 120 seconds has one of the lowest porosities of the various cements, while retaining good handling characteristics and excellent fatigue strength. .A Jasty M; Davies JP; O'Connor DO; Burke DW; Harrigan TP; Harris WH. .I 274687 .U 91004989 .S Clin Orthop 9101; (259):130-9 .M Age Factors; Aged; Bone Density; Bone Screws; Female; Fracture Fixation, Internal/AE/*MT; Hip Fractures/*SU; Human; Male; Osteoporosis/CO; Postoperative Complications; Reoperation; Retrospective Studies. .T Trochanteric fractures. Influence of reduction and implant position on impaction and complications. .P JOURNAL ARTICLE. .W A review of roentgenograms and charts was made of 532 trochanteric fractures treated by the sliding-screw technique. According to Evans' modified classification, 65% of the fractures were unstable. There was no breakage or bending of implants. Twenty (3.8%) reoperations were performed because of technical complications or nonunion. The Singh index revealed more unstable fractures and technical complications in hips with Grades 1-3 than in hips with Grades 4-6. Reoperation was more frequent if the screw tip was within 8 mm from the subchondral line in the superolateral quadrant or in the anteroproximal quadrant than if the screw ended farther from the subchondral line. Fifty-five (10.8%) of the lag screws migrated 2 mm or more. Postoperatively, the neck-shaft angle decreased more in unstable fractures than in stable fractures. The decrease in neck-shaft angle was less when the proximal fragment impinged medially on the shaft fragment. Unstable fractures with this type of reduction also impacted less than hips with anatomic reduction or medial reduction of the shaft fragment. Weight bearing did not significantly influence the degree of impaction. .A Larsson S; Friberg S; Hansson LI. .I 274688 .U 91004990 .S Clin Orthop 9101; (259):140-5 .M Adolescence; Aged; Aged, 80 and over; Bone Nails; Bone Plates; Bone Screws; Female; Femoral Neck Fractures/*SU; Follow-Up Studies; Fracture Fixation, Internal/AE/*MT; Fracture Fixation, Intramedullary/AE; Human; Male; Middle Age; Retrospective Studies. .T Subtrochanteric fractures. A retrospective analysis. .P JOURNAL ARTICLE. .W In a retrospective review of 107 patients treated during an eight-year period for subtrochanteric fractures, the average follow-up period was 25.5 months (range, six to 96 months). Comparisons of fracture patterns, fixation devices, and complications of osteosynthesis were made in an attempt to identify fixation devices that are best suited for the treatment of this difficult orthopedic problem. The Seinsheimer system of classification was used, and the fracture at risk was identified. Long spiral fractures with associated butterfly fragments in the osteopenic bone of elderly patients occurred most frequently, with complications of osteosynthesis and inherent instability. Despite the theoretic biomechanical advantages offered by the intramedullary systems, follow-up observations showed better results in patients with treatment by extramedullary devices. .A Lechner JD; Rao JP; Stashak G; Adibe SO. .I 274689 .U 91004991 .S Clin Orthop 9101; (259):146-56 .M Biomechanics; Human; Joint Instability/*PC; Knee Joint/*PH/SU; Knee Prosthesis/*; Range of Motion, Articular; Reoperation. .T The influence of joint line position on knee stability after condylar knee arthroplasty. .P JOURNAL ARTICLE. .W Using a special knee-testing device, ten knees obtained at autopsy were subjected to varus-valgus, anterior-posterior, and flexion-rotation analysis in the intact state and after total knee arthroplasty. The ten knees showed no significant change in stability after knee replacement when the joint line was maintained in its natural position. When the femoral component was repositioned 5 mm proximally and 5 mm anteriorly, a significant increase in laxity occurred during midflexion. When the joint line was shifted 5 mm distal and 5 mm posterior to its anatomic location, significant tightening occurred in midrange of motion. Coupled rotation of the tibia with knee flexion was decreased after surgery in all knees with no specific relationship to joint line position. Coupled rotation with varus-valgus testing, however, remained within the normal range through the first 30 degrees of flexion only when the joint line was restored to its normal anatomic position. Stability in condylar knee arthroplasty is in part dependent on position of the joint line. Surgical techniques that rely on restoring the flexion and extension gap without regard to joint line position may result in alteration of varus-valgus or anterior-posterior displacement in midrange flexion. .A Martin JW; Whiteside LA. .I 274690 .U 91004992 .S Clin Orthop 9101; (259):157-9 .M Aged; Case Report; Female; Human; Knee Prosthesis/*AE; Suction/*IS. .T Suction drainage tube entrapment in total knee arthroplasty. .P JOURNAL ARTICLE. .W Two cases of entrapment of suction drainage tubes between the femoral and tibial components were encountered after total knee arthroplasty. The first patient had an arthrotomy because it was believed that the tube was caught in a suture, and while attempting to remove it a portion remained trapped in the joint. At operation, flexion of the knee released the tubing. The second patient did not require reoperation because flexion of the knee released the tubing. .A Marmor L. .I 274691 .U 91004993 .S Clin Orthop 9101; (259):160-8 .M Biomechanics; Bone Plates; Bone Screws/*; Human; Knee Prosthesis/*; Prosthesis Failure; Tensile Strength; Tibia/*PH. .T Effects of screws and a sleeve on initial fixation in uncemented total knee tibial components. .P JOURNAL ARTICLE. .W Aseptic loosening of tibial components remains a serious problem in uncemented total knee arthroplasties. Achieving rigid initial fixation of porous-coated components is one of the most important factors in promoting bone ingrowth. The results of a biomechanical study for micromovement of the tibial component under posteroanterior shear and axial compressive loading are presented. Forty anatomic specimen tibiae were stress tested on a servohydraulic mechanical test machine to evaluate the effects of screws and a sleeve on initial fixation of the uncemented total knee tibial component. Twenty specimens were used for posteroanterior shear loading and 20 for anterolateral axial compressive loading. Four cancellous screws were inserted through holes of the tibial tray to pierce the cortex of the proximal tibia. The methylmethacrylate sleeve was applied to the central stem. Rigidity of fixation was significantly improved by the combination of screws and a sleeve. Bone strength was also an important factor affecting the quality of fixation. .A Miura H; Whiteside LA; Easley JC; Amador DD. .I 274692 .U 91004994 .S Clin Orthop 9101; (259):169-78 .M Biomechanics; Bone Nails/*; Bone Screws/*; Comparative Study; Knee Prosthesis/*; Prosthesis Failure; Tensile Strength; Tibia/PH. .T The effect of screws and pegs on the initial fixation stability of an uncemented unicondylar knee replacement. .P JOURNAL ARTICLE. .W Two uncemented unicompartmental tibial components were examined for initial fixation stability. A conventional design that employed a single posteriorly angled peg was compared with a new design that was held in place by cancellous bone screws. The components were implanted into the medial condyles of 12 preserved human tibiae, and a cyclic load was first applied anteromedially and then posteromedially. The screwed implants failed at significantly higher loads (1634.8 +/- 121.6 N, mean +/- standard error of the mean) than the pegged implants (1103.3 +/- 152.0 N). On application of a 19.6-N preload, the screwed implants moved significantly less than the pegged implants. Although the differences in micromotion and subsidence were not always significant, there were definite trends. The screwed implants had much lower levels of temporary and permanent displacement compared with the pegged implants for all load levels from the initial load of 245.2 N up to and including the failure load. When the motion that resulted from moving the load from the anterior position to the posterior position was examined, the screwed implant's average total motion was less than 10 microns compared with almost 135 microns for the pegged implant after the 245.2-N load cycle. For the cycle before failure, the screwed implant's average motion increased to less than 29 microns, whereas the pegged implant's average total motion was almost 354 microns. From this information it appears clear that screws provide better initial fixation stability than angled pegs for uncemented unicondylar tibial components. .A Kaiser AD; Whiteside LA. .I 274693 .U 91004995 .S Clin Orthop 9101; (259):179-82 .M Adult; Aged; Aged, 80 and over; Bacterial Infections/ET/*RI; Bone and Bones/RI; Female; Human; Indium Radioisotopes/*DU; Knee Prosthesis/*AE; Leukocyte Count; Male; Middle Age; Prosthesis Failure; Surgical Wound Infection/RI. .T The value of indium 111 leukocyte scanning in the evaluation of painful or infected total knee arthroplasties. .P JOURNAL ARTICLE. .W Evaluation of painful total knee arthroplasties (TKAs) for infection can be difficult. Indium 111 (111In) leukocyte bone scanning provides a minimally invasive technique for evaluation of possible infection. Thirty-eight patients with a painful TKA who had surgical exploration after 111In leukocyte scanning were reviewed. The scan had an accuracy of 84%, a sensitivity of 83%, and a specificity of 85%. The 111In leukocyte scans must be interpreted in conjunction with the clinical evaluation of the patient because they are less accurate for study of TKAs than of total hip arthroplasties. .A Rand JA; Brown ML. .I 274694 .U 91004996 .S Clin Orthop 9101; (259):18-22 .M Adolescence; Child; Diagnosis, Differential; Female; Human; Male; Spinal Diseases/*DI/TH. .T Pediatric spondyloarthropathies. .P JOURNAL ARTICLE; REVIEW; REVIEW LITERATURE. .W Seronegative spondyloarthropathies in childhood are often misdiagnosed as juvenile rheumatoid arthritis, but recognition of their distinct clinical manifestations and unique underlying pathophysiologies can aid in making a proper diagnosis. Ankylosing spondylitis, Reiter's syndrome, psoriatic arthritis, and the arthritis associated with inflammatory bowel disease are arthritides most often found in young adults, but they may also be present in children. Extraarticular manifestations include inflammation of the eyes, skin, gastrointestinal tract, and genitourinary tract associated with inflammation of the entheses. The proper diagnosis will allow for treatment regimens that differ from those usually used for juvenile rheumatoid arthritis. Early diagnosis and treatment often lead to an early recovery and a return to normal daily activities. .A Kredich D; Patrone NA. .I 274695 .U 91004997 .S Clin Orthop 9101; (259):183-91 .M Anterior Cruciate Ligament/*IN/PH; History of Medicine, 20th Cent.; Human; Immobilization; Knee Injuries/*SU/TH; Orthopedics/HI. .T Paradoxes in the history of the anterior cruciate ligament. .P HISTORICAL ARTICLE; JOURNAL ARTICLE. .W A historic review of anterior cruciate ligament (ACL) investigation reveals two important paradoxes. (1) Ideas and concepts recently proposed were first put forth much earlier. (2) Controversy regarding this ligament continues despite the increased amount of information available. Much of the recent ACL literature, although regarded as newly discovered, has its roots in far older, and apparently forgotten or overlooked, work. Examples include: (1) ACL intactness is best tested at full extension; (2) hemarthrosis and ACL rupture are closely associated; and (3) ACL rupture sometimes masquerades as a minor injury. Additionally, early investigators achieved notable advances in surgical techniques. These contributions disappeared from the literature for two major reasons. First, early investigators observed few patients, with typical practitioners rarely seeing ACL injuries, and consequently, little data existed to support their observations. Second, observations could not be confirmed until the advent of widespread, successful surgery. Undoubtedly, orthopedists now know much more about the ACL, yet many issues remain controversial. Does the ACL perform a vital function? What is the efficacy of operative versus nonoperative treatment? What are the relative merits of direct repair, intraarticular substitutes, and extraarticular nonanatomic procedures? The origins and continued existence of controversy stem from several sources, including the less than rigorous study design and the scarcity of natural history, long-term follow-up studies, and basic science studies. The perception of the ACL as a simple structural unit has also perpetuated this controversy.(ABSTRACT TRUNCATED AT 250 WORDS) .A Wroble RR; Brand RA. .I 274696 .U 91004998 .S Clin Orthop 9101; (259):192-9 .M Adolescence; Adult; Anterior Cruciate Ligament/*IN; Athletic Injuries/RH; Braces; Female; Human; Immobilization; Knee Injuries/*RH; Male; Menisci, Tibial/IN; Middle Age; Prognosis. .T The outcome of nonoperatively treated complete tears of the anterior cruciate ligament in active young adults. .P JOURNAL ARTICLE. .W The results of nonoperative treatment of 72 patients with complete anterior cruciate ligament (ACL) tears, documented by examination under anesthesia and arthroscopy, were evaluated. All patients had an acute injury with hemarthrosis in a previously normal knee. Patients having meniscal repair were excluded as were those with collateral or posterior cruciate ligament tears or associated fractures. Treatment in all cases consisted of a standard protocol of early rehabilitation and bracing. A detailed rating of symptoms and function was performed at an average of 38 months postinjury (range, eight to 84 months). Overall results were 11% excellent, 20% good, 15% fair, and 54% poor. Thirty-five percent had ACL reconstruction during the follow-up period. Results indicate that young adults who return to a vocation requiring strenuous physical activity frequently can expect unsatisfactory results after nonoperative treatment of an acute complete tear of the ACL. .A Barrack RL; Bruckner JD; Kneisl J; Inman WS; Alexander AH. .I 274697 .U 91004999 .S Clin Orthop 9101; (259):200-3 .M Adult; Case Report; Football/IN; Human; Knee Injuries/*DI; Male; Muscles/IN; Tendon Injuries/DI. .T Isolated avulsion of the biceps femoris insertion. A case report. .P JOURNAL ARTICLE. .W The clinical, roentgenographic, and operative findings of an isolated biceps femoris avulsion in a 21-year-old man demonstrated the significance of the static stabilizers about the knee, menisci, and articular cartilage. Examination of the dynamic structures about the knee, however, may present a diagnostic problem. A systematic examination of the musculature (hamstrings, quadriceps, and patellofemoral mechanism) should be included in the evaluation of every acute knee injury. Special attention should be given to the surface anatomy as well as function of the knee. .A Sebastianelli WJ; Hanks GA; Kalenak A. .I 274698 .U 91005001 .S Clin Orthop 9101; (259):210-5 .M Adolescence; Adult; Aged; Bone Plates; Bone Screws; Female; Follow-Up Studies; Fracture Fixation, Internal/*MT; Human; Immobilization; Male; Middle Age; Postoperative Complications/ET; Prognosis; Retrospective Studies; Tibial Fractures/RH/*TH. .T Factors influencing the results of open reduction and internal fixation of tibial plateau fractures. .P JOURNAL ARTICLE. .W Forty-three displaced tibial plateau fractures were treated with open reduction and internal fixation. The fractures were classified into four groups, and the clinical results were evaluated using a standard 100-point knee rating system. The average follow-up period after surgery was 2.7 years. Overall there were 35 excellent, five good, three fair, and no poor results. In five of eight knees with a less than excellent score, the results were due to the technique of fracture fixation or the absence of a bone graft. There were ten postoperative complications, but only one ultimately affected the clinical result. Fourteen patients required removal of implants. Roentgenographic analysis showed that six knees had mild degenerative changes, two had moderate, and two had severe degenerative changes. There was no statistically significant association between the fracture type and a less than excellent result. The absence of bone grafting, however, was associated with a less than excellent result. Bicondylar fractures had a mean range of motion of 110 degrees, 18 degrees less than that of all other types of fracture combined. .A Lachiewicz PF; Funcik T. .I 274699 .U 91005002 .S Clin Orthop 9101; (259):216-22 .M Adult; Bone Regeneration/*; Electric Stimulation Therapy/*/AE; Female; Follow-Up Studies; Fractures, Ununited/RA/*TH; Human; Male; Middle Age. .T A ten-year review of treatment of delayed union and nonunion with an implanted bone growth stimulator. .P CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY. .W A ten-year clinical and roentgenographic review was conducted on the patients in the original Australian multicenter trial that evaluated use of an implantable bone growth stimulator for delayed union and nonunion. Of the original 81 patients, 38 patients were located, seven patients had died from unrelated causes, and 36 were unlocatable. Of the 38 patients located, 37 patients (representing 38 fractures) participated in a detailed clinical review and had a roentgenographic assessment. All fractures had remained united, and normal bone remodeling had occurred. There were no adverse effects of the generator or cathode wire. Six patients initially reported as failures had healed after further surgical intervention. Thus, normal osteogenesis occurs in association with electrical stimulation using an implantable bone growth stimulator. This ten-year review supports the long-term safety and effectiveness of this technique in treating nonuniting fractures. .A Cundy PJ; Paterson DC. .I 274700 .U 91005003 .S Clin Orthop 9101; (259):223-32 .M Animal; Bone Development/*PH; Cartilage/*PH; Cells, Cultured; Chickens; Mice; Mice, Nude; Osteoblasts/PH; Periosteum/CY/*GD. .T In vivo osteochondrogenic potential of cultured cells derived from the periosteum. .P JOURNAL ARTICLE. .W Periosteal cells were isolated from young chicks, introduced into cell culture, subcultured, and then inoculated into athymic, nude mice to test the in vivo osteochondrogenic potential of cultured periosteal cells. In monolayer cultures, the adherent periosteal cells showed fibroblastlike morphology and overtly expressed neither osteogenic nor chondrogenic phenotypes. Cultured cells inoculated heterotopically into nude mice eventually gave rise to bone tissue at the subcutaneous injection site. The process of bone formation occurred through two different mechanisms: intramembranous bone formation at the peripheral portion of the inoculum early and endochondral bone formation in the central portion later. Frozen, preserved periosteal cells also formed bone after introduction into nude mice in the same temporal histologic sequence as the unfrozen cells. Cultured chick muscle fibroblasts from donors that were the same age as controls did not form bone or cartilage when inoculated under identical conditions to those of cultured periosteal cells. These results suggest that periosteum of young chicks contains subsets of progenitor cells that possess the potential to differentiate directly into osteoblasts or chondrocytes when inoculated in vivo. Importantly, this potential is retained after enzymatic isolation, cell culture, subculturing, and freeze preservation. .A Nakahara H; Bruder SP; Goldberg VM; Caplan AI. .I 274701 .U 91005004 .S Clin Orthop 9101; (259):23-30 .M Agammaglobulinemia/CO; Arthritis, Juvenile Rheumatoid/*IM; Autoantibodies/AN; Child; Human; Support, Non-U.S. Gov't. .T Immunologic abnormalities of juvenile arthritis. .P JOURNAL ARTICLE; REVIEW; REVIEW LITERATURE. .W Many immunologic abnormalities have been found in children with all forms of chronic arthritis, but few are clinically useful or well understood. However, in children with arthritis it is important to distinguish among those with rheumatoid factor, antinuclear antibodies, or hypogammaglobulinemia. Rheumatoid factor is specific for adult-type rheumatoid arthritis; the presence of antinuclear antibodies increases the likelihood that the child may develop uveitis; and hypogammaglobulinemia may be associated with complicating infections. Other unusual antibodies, autoantibodies, antigen-antibody complexes, and complement activation products are found in children with arthritis, but none of these define a diagnostic or consistent group of diseases. Similarly, changes in the numbers of immunologically active cells and regulating mechanisms occur but not in specific patterns. As yet, none of the known immunologic abnormalities explain the pathogenesis of these diseases and only a few appear disease specific. .A Miller JJ 3d. .I 274702 .U 91005005 .S Clin Orthop 9101; (259):233-8 .M Antibodies, Monoclonal/DU; Bone Neoplasms/CH/*PA; Chondrosarcoma/PA; Fibroma/PA; Fibrous Dysplasia of Bone/*PA; Human; Neoplasm Proteins/AN/*PH; Osteoma/PA; Osteosarcoma/PA; Proteins/AN/*PH. .T The relationship between bone morphogenetic protein and neoplastic bone diseases. .P JOURNAL ARTICLE. .W The monoclonal antibody against bovine bone morphogenetic protein was used for demonstration of bone morphogenetic protein (BMP) in neoplastic bone diseases. The avidin-biotin-peroxidase complex method demonstrated that BMP mainly exists in the cytoplasm of tumor cells of osteosarcoma and chondrosarcoma. Immunostaining showed that a majority of osteosarcomas and all of the chondrosarcoma cells contained a large quantity of BMP. Conversely, none of the fibrosarcomas showed positive staining. Thus, it was possible to differentiate osteosarcomas from fibrosarcomas by immunostaining. In fibrous dysplasia of bone, BMP was abundant in the fibrocellular tissue that had osteogenic activity. In contrast, fibrous tissue of ossifying fibroma showed weak positive staining; only the osteoblasts rimming the bone showed a positive reaction. Immunostaining showed that BMP was also detected in other neoplastic bone diseases such as osteoma, chondroma, and other tumors. .A Jin Y; Yang LJ. .I 274703 .U 91005006 .S Clin Orthop 9101; (259):239-44 .M Animal; Bone Matrix/PH; Bone Transplantation/*PH; Ethylene Oxide/PD; Growth Substances/*PH; Hydrogen-Ion Concentration; Osteogenesis/*PH; Postmortem Changes; Proteins/*PH; Rats; Rats, Inbred Strains; Temperature; Tissue Donors. .T Influence of postmortem time and temperature on osteoinductive activity of demineralized microperforated ethylene oxide-sterilized syngeneic bone implant in the rat. .P JOURNAL ARTICLE. .W Bone morphogenetic protein is labile and easily inactivated by many extracorporeal factors. It is crucial to establish whether delay in retrieval of donor bone and ambient holding temperature of the donor body influence osteoinductivity of bone left in situ. Of ten adult rats that were killed, five were kept at 4 degrees and five at room temperature. Femurs were harvested at 24, 36, 48, 72, and 168 hours. After processing, segments were implanted in 20 four-week-old syngeneic rats for 14 days. The level of osteoinduction was evaluated histologically. It was excellent in the 4 degrees group in the 24-, 36-, and 48-hour specimens but less advanced at 72 hours. Bone taken from the room temperature group showed findings identical to those kept at 4 degrees through 36 hours, but osteoinduction was less advanced at 48 hours and absent at 72 hours. No bone formed at 168 hours in either temperature group. The following observations were made. (1) Osteoinductivity of demineralized bone left in situ after death was unexpectedly stable. (2) Retrieval time was extended by donor cooling. (3) Microperforated demineralized bone actively induced new bone formation. (4) Ethylene oxide does not inhibit osteoinduction when correctly applied for sterilization. If confirmed in humans, retrieval of bone to be used for osteoinduction could be delayed for some hours, particularly if the donor was immediately refrigerated. This would increase the effective number of bone tissue donors and utilize an undeveloped resource. .A Moore TM; Artal R; Arenas M; Gendler E. .I 274704 .U 91005007 .S Clin Orthop 9101; (259):245-55 .M Animal; Cartilage, Articular/*DE/PP; Femur/PP; Immobilization/AE; Osteoarthritis/PP; Rabbits; Somatotropin/*PD; Tibia/PP. .T The influence of growth hormone on the reversibility of articular cartilage degeneration in rabbits. .P JOURNAL ARTICLE. .W Growth hormone has chondrogenic affects on normal as well as on damaged articular cartilage. In this study, the influence of growth hormone is investigated on early degenerative changes in the articular cartilage in 72 New Zealand white rabbits. Cartilage lesions were created in femoral condyles using an immobilization model. Cartilage damage was assessed using biochemical, histologic, and biomechanical criteria. Growth hormone had no influence on prevention of immobilization abnormalities but had a significant affect on healing of established lesions. .A Halbrecht J; Carlstedt CA; Parsons JR; Grande DA. .I 274705 .U 91005008 .S Clin Orthop 9101; (259):256-67 .M Adenosine Cyclic Monophosphate/ME; Alkaline Phosphatase/ME; Animal; Cell Line; Human; Mice; Mice, Nude; Osteoblasts/CY/*ME; Osteocalcin/*SE; Osteosarcoma/*ME/PA; Parathyroid Hormones/PD. .T A newly established human osteosarcoma cell line with osteoblastic properties. .P JOURNAL ARTICLE. .W A human osteosarcoma cell line, HuO9, was established from a tumor that was heterotransplanted into athymic nude mice. Antiserum against nude mouse spleen cells was added to the early passage cultures to eliminate the host fibroblastic cells. The cell line retained a high activity of liver/bone/kidney-type alkaline phosphatase (ALP) and secreted osteocalcin, i.e., bone gamma-carboxyglutamic acid-containing protein (BGP), into the medium. The addition of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) increased the ALP activity as well as the level of BGP secreted into the medium. The ALP of 1,25(OH)2D3-treated cells has the same inhibition characteristics to heat and amino acids as that of untreated cells. Synthetic human parathyroid hormone stimulated the production of intracellular adenosine 3',5'-cyclic monophosphate (cAMP) approximately 100-fold within five minutes. However, the stimulation was not observed with a synthetic human thyrocalcitonin. When HuO9 cells were transplanted into the back of a nude mouse, a tumor with an abundant osteoid formation and mineralization was produced. The results indicate that the HuO9 cell line expresses well-differentiated osteoblastic phenotypes. HuO9 is the first established human cell line to produce BGP, and it provides a useful model for the studies of osteoblasts and the regulatory mechanisms of BGP production. .A Kawai A. .I 274706 .U 91005009 .S Clin Orthop 9101; (259):268-76 .M Animal; Biomechanics; Calcium/PD; Dogs; Hyperaldosteronism/CO/ET; Hypothyroidism/CO; Joints/DE/PP; Prednisone/AE/*PD; Retrospective Studies; Spinal Diseases/ET; Spine/*DE/PP; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Effects of corticosteroids on mechanical strength of intervertebral joints and vertebrae in dogs. .P JOURNAL ARTICLE. .W Dogs with hyperadrenocorticism had a higher incidence of intervertebral joint disease, i.e., disc protrusion or spondylosis. In comparing cases of hyperadrenocorticism with age- and breed-matched controls with hypothyroidism, the incidence was significantly greater than expected. This was not seen, however, in beagle dogs in which the incidence was already high and attributed to chondrodystrophoid tendencies in this breed. To investigate the pathogenesis of this association and its possible relationship to steroid-induced osteopenia, adult dogs were given a placebo, prednisone, or prednisone plus calcium for six months. Torque testing of intervertebral joints revealed a consistent trend of lower force to failure in both prednisone-treated groups, but the difference was not statistically significant. In these dogs with mild to moderate hyperadrenocorticism, compression tests of intact vertebral bodies were not significantly different, but blocks of trabecular bone cut from the vertebral bodies failed at significantly lower compressive forces in both prednisone-treated groups compared with controls. Histomorphometric evaluation of lumbar vertebral trabecular bone revealed that the percentage of bone volume was not significantly decreased in the prednisone-treated groups. Nor was there any difference in the thickness or porosity of vertebral end-plates, which might contribute to weakening of intervertebral ligamentous insertions. .A Norrdin RW; Histand MB; Sheahan HJ; Carpenter TR. .I 274707 .U 91005010 .S Clin Orthop 9101; (259):277-81 .M Animal; Biomechanics; Bone Nails/*; Comparative Study; Dogs; Epiphyses, Slipped/PP/*SU; Femur/PP; Fracture Fixation, Internal/*MT. .T Biomechanical comparison of single- and double-pin fixation for acute slipped capital femoral epiphysis. .P JOURNAL ARTICLE. .W Biomechanics of pin fixation for acute slipped capital femoral epiphysis (SCFE) was studied in an in vitro immature canine model. Acute SCFE were created in 24 paired femurs. The paired specimens were pinned with either one or two pins and loaded to failure. Strength and stiffness of the paired limbs were expressed as percentages of the loads necessary to create the initial SCFE in the intact specimen. Strength and stiffness were equivalent statistically for the intact physis and the fractured physis fixed with two pins. Single pinning was only 83% as strong and 78% as stiff as the intact physeal plate. Double-pin fixation is recommended over single-pin fixation for acute SCFE. These data, however, should not be extrapolated to the clinical situation of fixation for chronic SCFE. .A Kruger DM; Herzenberg JE; Viviano DM; Hak DJ; Goldstein SA. .I 274708 .U 91005011 .S Clin Orthop 9101; (259):282-94 .M Animal; Biomechanics; Bone Lengthening/*MT; Electromyography; Osteotomy/MT; Sheep; Tibia/PP/SU. .T Biomechanical factors in the metaphyseal- and diaphyseal-lengthening osteotomy. An experimental and theoretic analysis in the ovine tibia. .P JOURNAL ARTICLE. .W A post hoc comparison of the mechanical factors that affected the outcome of experimental metaphyseal- and diaphyseal-lengthening osteotomies in sheep tibiae was performed. The resulting motions between bone segments at the metaphyseal and diaphyseal levels were estimated using measured fixator stiffnesses, postural muscle activity, ground reaction forces, and calculated internal and external loads. Relative displacements of bone segments of up to 2.8 degrees were estimated in postural activities; displacements were up to 4.9 times larger at the metaphyseal than at the diaphyseal osteotomy level. The results suggest that due to these increased motions, mechanically inferior conditions for healing at the metaphyseal-lengthening osteotomy level may counteract any supposedly superior biologic healing potential that the metaphyseal region of the bone may have compared with the diaphyseal region. These results correlate well with the clinical findings of the earlier animal study. .A Steen H; Fjeld TO; Miller JA; Ludvigsen P. .I 274709 .U 91005012 .S Clin Orthop 9101; (259):295-303 .M Adult; Bone Transplantation; Femur/*/SU; Follow-Up Studies; Fractures, Ununited/SU; Human; Methods; Osteomyelitis/DT/MI/*SU; Pseudomonas/IP; Staphylococcus/IP; Surgical Flaps; Tibia/*/SU. .T Results of treatment of tibial and femoral osteomyelitis in adults. .P JOURNAL ARTICLE. .W From January 1, 1971, to December 31, 1985, 425 patients with chronic osteomyelitis of the femur or tibia were seen at the authors' institution. The success rate in this recent experience was 84.4% compared with 50.9% in the authors' results published in 1970. A classification of chronic osteomyelitis is as follows: (1) hematogenous osteomyelitis; (2) osteomyelitis in united fractures (fracture with union); (3) osteomyelitis in nonunion (fracture with nonunion); and (4) postoperative or posttraumatic osteomyelitis in which bone was not fractured. For management of the scarring of surrounding soft tissue, there has been a change to excision of the scarred tissue and reliance on muscle flap, free-tissue transfer, or closure of soft tissues without irrigation with antibiotic solution. In recent years, free microvascular osseous grafts have permitted more aggressive resection of the involved osseous tissue. The predominance of gram-negative organisms and penicillin-resistant Staphylococcus aureus and the occurrence of methicillin-resistant S. aureus continue. .A Kelly PJ; Fitzgerald RH Jr; Cabanela ME; Wood MB; Cooney WP; Arnold PG; Irons GB. .I 274710 .U 91005013 .S Clin Orthop 9101; (259):304-11 .M Anatomy/*HI; Belgium; History of Medicine, 16th Cent.; Spain. .T The martyrdom of Doctor Andreas Vesalius. .P HISTORICAL ARTICLE; HISTORICAL BIOGRAPHY; JOURNAL ARTICLE. .W The development of modern medicine began in the 16th century when Dr. Andreas Vesalius overthrew the previously uncontested medical dogma of the Greek physician Galen. Medical progress had been hindered for more than a millennium by strict adherence to Galen's authority. Flemish-born Vesalius challenged the political and societal forces of the time. At the University of Padua, he studied and later taught human anatomy by performing dissections. His discoveries were published in 1543 in his monumental De Humani Corporis Fabrica. Controversy led to his resignation from the University of Padua. His magnum opus was interpreted as a challenge to both academia and the church. He went to Spain, where he served as personal physician to Emperor Charles V. After almost 20 years in Spain, he became involved in an unfortunate incident that incurred the condemnation of the Inquisition. The royal court's intervention saved Vesalius from being burned at the stake, however, and he was ordered to make a pilgrimage to Jerusalem to atone for his error. On the return voyage, he became ill and died on the Greek island of Zante. .A Lasky II. .I 274711 .U 91005014 .S Clin Orthop 9101; (259):31-7 .M Arthritis, Juvenile Rheumatoid/BL/*ME; Cartilage, Articular/CY/*PP; Child; Human; Support, U.S. Gov't, P.H.S.; Synovial Fluid/PH. .T Soluble mediators of articular cartilage degradation in juvenile rheumatoid arthritis. .P JOURNAL ARTICLE; REVIEW; REVIEW LITERATURE. .W Juvenile rheumatoid arthritis (JRA) involves a wide range of joint tissues. Tissue changes include proliferation of synovial cells, alterations in synovial fluid, and degradation of articular cartilage. Synovial cell proliferation results in increased numbers of fibroblasts and lymphocytes. Changes in the synovial fluid include increased content of antibodies, altered complement ratios, increased levels of factors stimulating cartilage-mediated proteoglycan degradation, and decreased levels of insulinlike growth factor I. Levels of cytokine such as interleukin-1 and interleukin-2 vary with cell culture and assay technique. Cartilage degradation is apparent from increased quantities of proteoglycan and glycosaminoglycan in serum and synovial fluid. Type II collagen peptide antibodies are also prevalent in JRA patients. Cartilage degradation appears linked to factors in JRA synovial fluid. Conditioned medium of peripheral blood mononuclear cells from patients with JRA also stimulates increased release of cartilage proteoglycan. Thus, the outcome in JRA likely reflects activities of interacting soluble factors that directly influence cartilage homeostasis. .A Smith RL. .I 274712 .U 91005015 .S Clin Orthop 9101; (259):38-45 .M Animal; Arthritis, Rheumatoid/*; Disease Models, Animal/*; Mice; Rabbits; Rats; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Animal models of chronic inflammatory arthritis. .P JOURNAL ARTICLE; REVIEW; REVIEW LITERATURE. .W The use of animals has been indispensable to the investigation of the etiology, pathophysiology, and treatment of juvenile arthritis. Because of ethical concerns about studying children, the difficulty of obtaining tissue, and the heterogeneous manifestations and protean course of chronic arthritis in childhood, the scope of potential research has been severely limited. This brief review summarizes a few of the animal models most commonly used in chronic inflammatory arthritis research: subcutaneous air pouch, antigen-induced (including arthritogenic infectious agent), and spontaneous models. In the spontaneous and antigen-induced animal models of arthritis, local and systemic immunoregulatory abnormalities clearly play a major role in the pathogenesis of arthritis. By elucidating the immune response to those antigens, as well as the role of genetics and environment, the pathogenesis of juvenile rheumatoid arthritis may be better understood. At the present time, however, the complexity of these models precludes more definitive interpretation and extrapolation to human diseases. .A Magilavy DB. .I 274713 .U 91005016 .S Clin Orthop 9101; (259):4-10 .M Arthritis, Juvenile Rheumatoid/*HI; Child; Female; History of Medicine, 19th Cent.; History of Medicine, 20th Cent.; Human; Male. .T On a form of chronic joint disease in children. 1896 [classical article] .P CLASSICAL ARTICLE; HISTORICAL ARTICLE; HISTORICAL BIOGRAPHY; JOURNAL ARTICLE. .A Still GF. .I 274714 .U 91005017 .S Clin Orthop 9101; (259):46-50 .M Arthritis, Juvenile Rheumatoid/CO/*PP; Child; Growth Disorders/*; Human. .T Growth abnormalities in children with juvenile rheumatoid arthritis. .P JOURNAL ARTICLE; REVIEW; REVIEW LITERATURE. .W Growth abnormalities in juvenile rheumatoid arthritis can be divided into two groups: local and systemic. Local disorders of growth often result in increased bone length and bone age or in marked decreases in longitudinal growth due to immobilization, premature epiphyseal closure, or fusion. Common growth defects seen in the knee, hand, wrist, hip, spine, and jaw are discussed. Systemic growth delay is most commonly secondary to active disease or treatment with corticosteroids. Nutritional aspects such as decreased appetite, reduced caloric intake, metabolic caloric requirements greater than available intake, or lack of essential vitamins could be the cause for decreased weight and stature. .A White PH. .I 274715 .U 91005018 .S Clin Orthop 9101; (259):51-9 .M Child; Chronic Disease; Human; Rheumatic Diseases/*CO; Uveitis, Anterior/DT/*ET. .T Ocular complications of rheumatic diseases of childhood. .P JOURNAL ARTICLE; REVIEW; REVIEW LITERATURE. .W The association between inflammatory ocular and articular disease is a strong one, although the pathogenesis of this relationship is obscure. For the physician or surgeon caring for children with chronic arthritis, awareness of the risk of chronic asymptomatic anterior uveitis is essential if early diagnosis, treatment, and prevention of visual impairment are to be accomplished. This is particularly true for children with pauciarticular-onset juvenile rheumatoid arthritis or psoriatic arthritis. Acute symptomatic anterior uveitis is characteristic of disorders such as ankylosing spondylitis. Whereas this disease is initially more unpleasant for the child, it has a good long-term prognosis. .A Petty RE. .I 274716 .U 91005019 .S Clin Orthop 9101; (259):60-9 .M Anti-Inflammatory Agents/*TU; Anti-Inflammatory Agents, Non-Steroidal/*TU; Arthritis, Juvenile Rheumatoid/*DT; Child; Human; Immunization, Passive; Immunosuppressive Agents/TU. .T Medical treatment of juvenile arthritis. .P JOURNAL ARTICLE; REVIEW; REVIEW LITERATURE. .W The range of medications available to treat juvenile arthritis has markedly expanded over the past 15 years. Multiple new nonsteroidal antiinflammatory drugs (NSAIDs) are available in the United States, although only a few are approved for use in children, and none have been proven to be significantly better than aspirin in suppressing inflammation. The average time before significant improvement is noticed is over 30 days in the 50% of the children who respond to any NSAID within three months. The percentage of responders progressively increases with the length of therapy, so treatment should be continued until one is reasonably certain that improvement will not occur before changing medication. In the more severely involved child, gold and other disease-modifying medications are used. However, it has been difficult to prove the value of these medications in controlled studies because of the high rate of significant improvement in the control group treated with NSAIDs. In preliminary studies, methotrexate appears to have significant benefit in children who have failed other treatments. Other newer therapies, such as intravenous gammaglobulin, have only been used in a small number of patients and have not as yet been proven beneficial. .A Fink CW. .I 274717 .U 91005020 .S Clin Orthop 9101; (259):70-5 .M Arthritis, Juvenile Rheumatoid/CO/*SU; Child; Human; Joints/*SU. .T The surgery of juvenile chronic arthritis. An overview. .P JOURNAL ARTICLE; REVIEW; REVIEW LITERATURE. .W Surgery now has a well-established place in the management of childhood arthritis. However, satisfactory results can only be achieved by a team of medical experts composed of a pediatric rheumatologist, an orthopedic surgeon, an anesthetist, a physiotherapist, and others who are knowledgeable about the particular problems of juvenile chronic arthritis. An aggressive team approach offers the best available help. .A Swann M. .I 274718 .U 91005021 .S Clin Orthop 9101; (259):76-82 .M Adolescence; Arthritis, Juvenile Rheumatoid/BL/*SU; Child; Child, Preschool; Follow-Up Studies; Human; Joints/SU; Methods; Postoperative Complications; Retrospective Studies; Synovial Membrane/*SU. .T A three-year retrospective study of synovectomies in children. .P JOURNAL ARTICLE. .W The aim of this study was to evaluate the results of synovectomies in children with juvenile arthritis. Five hundred twenty-eight synovectomies and tenosynovectomies were performed over a period of 13 years. The patients were followed for one, two, three, five, and ten years postoperatively. The evaluation after three years was chosen as the basis for this article. One hundred twenty-five children with arthritis who were not evaluated three years postoperatively had less severe arthritis, both locally and generally, than the evaluated group of 389. The rate for good results and tolerability was high at one, two, and three years postoperatively but decreased with time; more patients went from good results to poor rather than vice versa. Global assessment, soft-tissue swelling, and limitation of movement seemed to be the best parameters for evaluating the results of synovectomies. It appears necessary to wait at least three years to evaluate the long-term effect of synovectomies. .A Ovregard T; Hoyeraal HM; Pahle JA; Larsen S. .I 274719 .U 91005022 .S Clin Orthop 9101; (259):83-91 .M Arthritis, Juvenile Rheumatoid/*SU; Child; Hip Prosthesis/*/AE; Human; Knee Prosthesis/*/AE. .T Total hip and knee arthroplasty in juvenile rheumatoid arthritis. .P JOURNAL ARTICLE; REVIEW; REVIEW LITERATURE. .W Total hip or knee arthroplasty is indicated in patients with juvenile rheumatoid arthritis when there is marked functional impairment and/or severe disabling pain from advanced structural hip or knee joint involvement. Relief of pain and dramatic improvement in function can be achieved in most patients. When both the hip and knee are involved, hip arthroplasty should probably be done first. Regional anesthesia is preferable. Careful preoperative planning is essential because custom prostheses are often required. Small bone size, osteoporosis, and soft-tissue contractures make the surgery technically demanding. Skeletal immaturity is not an absolute contraindication to surgery. Component loosening is the most frequent late complication in hip arthroplasty. It is less common in condylar metal-to-plastic knee arthroplasty in which patellar complications predominate. Cementless arthroplasty has an evolving role in the patient with juvenile rheumatoid arthritis and, to date, is more often used in the hip than in the knee. .A Scott RD. .I 274720 .U 91005023 .S Clin Orthop 9101; (259):92-9 .M Adolescence; Adult; Child; Child, Preschool; Female; Follow-Up Studies; Human; Laminectomy/AE/*MT; Male; Postoperative Complications/*PC; Spinal Cord Neoplasms/SU; Spinal Fusion/*MT; Spinal Stenosis/SU. .T Combined laminoplasty and posterolateral fusion for spinal canal surgery in children and adolescents. .P JOURNAL ARTICLE. .W Spinal deformities, especially kyphosis and instability, after laminectomy for tumors and other diseases, are major clinical problems. Since 1981, combined laminoplasty and posterolateral fusion for the prevention of postlaminectomy spinal deformities was performed on eight male and two female patients aged two to 26 years (average, 13.9 years). The follow-up period was from six months to seven years and three months (average, three years and five months). Two patients died six and ten months postoperatively because of brain metastases (astrocytoma) and lung metastases (neuroblastoma), respectively. Good alignment with no instability of the cervical or thoracic spine was obtained for all patients, including the two who died. Laminoplasty combined with posterolateral fusion was found to be very effective in preventing the development of spinal deformities after spinal canal surgery for spinal cord tumors or other diseases in children and adolescents. .A Shikata J; Yamamuro T; Shimizu K; Saito T. .I 274721 .U 91005050 .S Clin Pediatr (Phila) 9101; 29(8):434-7 .M Case Report; Human; Infant; Male; Pedigree; Wiskott-Aldrich Syndrome/*DI/GE. .T Wiskott-Aldrich syndrome. A case report. .P JOURNAL ARTICLE. .W This paper presents a report on a child with Wiskott-Aldrich syndrome. The clinical picture and laboratory findings are characteristic of this disease. The prevailing symptoms have included recurrent respiratory and alimentary tract infections, seborrhic dermatitis-type skin lesions, and thrombocytopenia. Humoral and cellular immunological disturbances have been noted, and the pedigree pattern is very characteristic. .A Dubiel A; Szczerbinski T; Kurtyka Z; Kowalczyk D. .I 274722 .U 91005051 .S Clin Pediatr (Phila) 9101; 29(8):438-43 .M Bacterial Infections/BL/CO/*DI; Body Temperature; Fever/*ET; Human; Infant; Infant, Newborn; Predictive Value of Tests; Sensitivity and Specificity. .T Febrile infants less than eight weeks old. Predictors of infection. .P JOURNAL ARTICLE. .W Febrile infants less than eight weeks old frequently are admitted and receive parenteral antibiotics for treatment of possible sepsis. The authors assess 52 infants less than eight weeks old with a rectal temperature of 38.1 degrees C or higher as having either a readily identifiable focus of infection by physical examination, appearing "toxic" without a focus, or appearing well. The authors screened patients by using white blood cell (WBC) counts, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and chest radiographs in addition to blood, cerebrospinal fluid and urine cultures. The authors found a 9.6% incidence of bacteria in the 52 infants evaluated, with a 4.3% incidence in those febrile infants who appeared well. Five patients had positive blood cultures with Group B B Hemolytic streptococcus (four patients), and Viridans streptococcus (one patient). A clinical assessment of toxicity and a total band count greater than or equal to 0.5 x 10(3) cells/uL together were sensitive indicators of bacteremia, as were toxicity and a positive CRP. A "toxic" appearance, a WBC count greater than or equal to 15 x 10(3) cells/uL and an ESR greater than 30 were specific indicators of bacteria. Based on these data, identification of bacteremia in febrile infants may be possible with clinical assessment and screening laboratory tests. Because of the relatively small sampling size of this study, the authors feel that evaluation of a larger number of patients is warranted to evaluate these sensitivities in a more diffuse patient population. .A Broner CW; Polk SA; Sherman JM. .I 274723 .U 91005053 .S Clin Pediatr (Phila) 9101; 29(8):445-7 .M Antibiotics/*TU; Bacterial Infections/*DI/DT; Human; Infant, Newborn; Retrospective Studies; Septicemia/*DI/DT. .T Superficial cultures in neonatal sepsis evaluations. Impact on antibiotic decision making. .P JOURNAL ARTICLE. .W The authors performed a retrospective analysis of neonatal superficial cultures and their effect on antimicrobial decision making during a nine-month period at Nashville General Hospital. They obtained and reviewed charts of infants (n = 66) having paired superficial (skin and/or gastric aspirate) and deep (blood and cerebrospinal fluid) cultures for the evaluation of early-onset sepsis. Superficial cultures were positive for pathogens (any streptococcus or enteric gram-negative) in 15% (10/66) of cases. Antimicrobial decision making was affected in only one of these cases, and in a seemingly inappropriate manner. In summary, there was no evidence or review that superficial cultures used in sepsis evaluation influenced physician antimicrobial decision making; in one case they may have led to unnecessary antibiotic exposure. .A Zuerlein TJ; Butler JC; Yeager TD. .I 274724 .U 91005054 .S Clin Pediatr (Phila) 9101; 29(8):448-50 .M Case Report; Child; Child, Preschool; Chloroquine/*AE; Human; Psychoses, Substance-Induced/*ET. .T Toxic psychosis due to chloroquine--not uncommon in children. .P JOURNAL ARTICLE. .W Toxic psychosis due to Chloroquine is a relatively uncommon occurrence in childhood. This entity must be kept in differential diagnosis in a case of unexplained psychosis, before resorting to a sophisticated array of detailed investigations. The purpose of this is to familiarize pediatricians with this relatively uncommon entity. The authors encountered four cases of psychosis with a wide variety of symptomatology over a period of the past 18 months. .A Garg P; Mody P; Lall KB. .I 274725 .U 91005056 .S Clin Pediatr (Phila) 9101; 29(8):457-63 .M Adolescence; Adult; Biopsy, Needle/*MT; Child; Child, Preschool; Human; Infant; Infant, Newborn; Intraoperative Period; Male; Ultrasonography/*. .T Ultrasound guidance. For interventional and intraoperative techniques in infants and children. .P JOURNAL ARTICLE. .W Since the advent of improved realtime ultrasound (US) imaging and the availability of the needle biopsy attachment, US-guided percutaneous biopsy and the drainage procedure can be performed safely in the pediatric patient. The authors review their experience over 3 years using US-guided interventional techniques in 96 children aged 5 days to 21 years. A wide variety of procedures were performed and included renal biopsy, nephrostomy tube placement, renal mass biopsy, puncture of bladder sinus tract and pancreatic pseudocyst, ventriculoperitoneal shunt placement and intraoperative localization of brain or renal tumor and renal calculi. No complication occurred. US can be safely and accurately used as guide for interventional procedures in children as long as the area of interest can be clearly demonstrated and the depth and necessary angle of needle insertion can be predetermined as feasible. .A Rosenberg HK; Sherman NH. .I 274726 .U 91005057 .S Clin Pediatr (Phila) 9101; 29(8):465-7 .M Adolescence; Analysis of Variance; Educational Status/*; Human; Infant, Low Birth Weight/*; Infant, Newborn; Retrospective Studies. .T The correlation between low birth weight and learning traits in senior school pupils--a retrospective survey. .P JOURNAL ARTICLE. .W The purpose of this study was to establish whether a correlation exists between childrens birth weight and their scholastic achievements in high school. This correlation has previously only been investigated only in primary school children and it was felt that it would be interesting to observe whether schooling changed the known status. The records of 718 children were reviewed and there appears to be a statistically significant disability for low birth weight children in the study of exact sciences and foreign languages whilst no significant differences were noted in the humanities and sport. .A Brook U; Shemesh A; Heim M. .I 274727 .U 91005058 .S Clin Pediatr (Phila) 9101; 29(8):468-70 .M Breast Feeding/*; Failure to Thrive/*ET; Female; Human; Infant; Infant, Newborn; Male; Risk Factors. .T Underlying illness associated with failure to thrive in breastfed infants. .P JOURNAL ARTICLE. .W Over a four-year period in a suburban pediatric practice, 38 infants aged six months or less were identified with failure to thrive (FTT) while breast-feeding. In seven cases (18.4%), an associated organic illness was diagnosed. Only 2 of 28 breast-fed neonates (8%) were found to have FTT associated with another illness, as compared to 5 of 10 older infants (50%). Breast-fed infants with FTT, particularly those presenting after the first month of life, should be considered high risk for having other disease. Their clinical evaluation should include an appropriate search for organic illnesses. .A Lukefahr JL. .I 274728 .U 91005060 .S Clin Pediatr (Phila) 9101; 29(8):474-7 .M Case Report; Child Abuse/*DI; Diagnosis, Differential; Female; Gastrointestinal Hemorrhage/*DI; Human; Infant; Male; Munchausen Syndrome/*DI. .T Gastrointestinal bleeding in a 15 month old male. A presentation of Munchausen's syndrome by proxy. .P JOURNAL ARTICLE. .W Munchausen's syndrome by Proxy is a well-described entity that may not always be immediately considered in a complicated case. We describe this syndrome being portrayed through the guise of gastrointestinal bleeding in a 15 month old male and discuss not only the difficulty involved in solidifying this diagnosis but also the consequences that may occur should this diagnosis not be entertained. Failure to diagnose Munchausen's syndrome by proxy often results from failure to consider the diagnosis. These cases frequently have specific characteristics that allow seasoned clinicians to suspect the diagnosis. Once the diagnosis is considered, it is crucial to take steps to protect not only the index patient but also siblings who not infrequently are also recipients of this life threatening form of child abuse. .A Mills RW; Burke S. .I 274729 .U 91005061 .S Clin Pediatr (Phila) 9101; 29(8):478 .M Case Report; Child; Chondroma/*PA/RA; Female; Foramen Magnum/*PA/RA; Human; Skull Neoplasms/*PA/RA; Tomography, X-Ray Computed. .T Chondroma in the foramen magnum. .P JOURNAL ARTICLE. .A Sharma V; Newton G. .I 274730 .U 91005062 .S Clin Pediatr (Phila) 9101; 29(8):479-84 .M Case Report; Diagnosis, Differential; Fatty Acids/BL; Female; Fibroblasts; Human; Infant; Male; Metabolism, Inborn Errors/*DI/GE; Microbodies/*ME; Phenotype; Phytanic Acid/BL; Zellweger Syndrome/*DI/GE. .T Two siblings with phenotypes mimicking peroxisomal disorders but with discordant biochemical findings. .P JOURNAL ARTICLE. .W The authors present a report on two sibling with a nearly identical phenotype mimicking peroxisomal disorder but with totally discordant biochemical findings. In an attempt to confirm the diagnosis of a peroxisomal disorder, plasma levels of very long chain fatty acids (VLCFA) and phytanic acid were determined. In addition, fibroblasts profile of VLCFA and plasmalogen levels were evaluated for Case 2. Pathomorphological examinations represented by lymph node and kidney biopsies as well as postmortem examinations of liver, adrenals and brain were performed in Case 1. The phenotypes of both siblings showed marked resemblance to those observed in children with Zellweger syndrome. The results of biochemical tests performed in Case 1, together with abundant peroxisomes in the liver and the wide spectrum of clinical abnormalities suggest pseudo-Zellweger or Zellweger-like syndromes, but no conclusive data have been found. The plasmalogen level in fibroblasts as well as the fibroblasts profile of VLCFA noted in Case 2 were within the normal range, thus excluding the possibility of a peroxisomal disorder. The striking phenotype resemblance of the siblings mimicking Zellweger, together with discordant biochemical findings, are difficult to explain on the basis of currently available tests. .A Pietrzyk JJ; Turowska-Heydel D; Klimek M; Kaczmarski F; Kaluza J. .I 274731 .U 91005063 .S Clin Pediatr (Phila) 9101; 29(8):485 .M Diagnosis, Differential; Human; Infant; Meningitis/*DI; Spinal Puncture. .T Diseases that mimic meningitis [letter; comment] .P COMMENT; LETTER. .A Dave A. .I 274732 .U 91005064 .S Clin Pediatr (Phila) 9101; 29(8):485-6, 487 .M Autonomic Nervous System/*PP; Child; Child Behavior/*; Human; Respiration/*. .T Pallid breath-holding spells; evaluation of the autonomic nervous system [letter; comment] .P COMMENT; LETTER. .A Ramet J; Hauser B; Schmedding E. .I 274733 .U 91005113 .S Compr Ther 9101; 16(7):20-7 .M Adult; Case Report; Euthyroid Sick Syndromes/DI; Female; Human; Hyperthyroxinemia/DI; Hypothyroidism/DI; Male; Middle Age; Thyroid Diseases/*DI; Thyroid Function Tests/*. .T Tests of thyroid function: update in the diagnosis and management of thyroid disease. .P JOURNAL ARTICLE. .W Current thyroid function tests give the clinician powerful tools for the accurate assessment of thyroid status in the majority of patients encountered. There are, however, a small number of clinical situations in which there appear to be inconsistencies in the interrelationship of the thyroid function tests and/or in which they are apparently inappropriate to the clinical status of the patient. In most instances, there is a rational explanation for these observed alterations. The application of this information should allow clinicians to further refine their diagnostic accuracy and thereby enable them to proceed with an appropriate therapeutic or management program. .A Meek JC. .I 274734 .U 91005114 .S Compr Ther 9101; 16(7):28-32 .M Human; Hypothyroidism/DI/*DT; Patient Compliance; Thyroid Function Tests; Thyroid Hormones/AD/TU. .T Management of primary hypothyroidism. .P JOURNAL ARTICLE. .W Primary hypothyroidism is a common condition requiring lifelong treatment and monitoring. The type and amount of thyroid hormone replacement, selection of laboratory tests, and timing of office visits are all important for optimizing patient well-being and reducing the costs of medical care. The aim of treatment is to bring the patient to the euthyroid state. Currently this is defined as a normal serum concentration of TSH by recently developed sensitive and specific immunometric assays, and is accomplished by titrating the dose of levothyroxine and changing it not more often than at 4- to 6-week intervals. As an indicator of euthyroidism, the sensitive TSH assay has advantages over tests of serum T4, FT4I, T3, FT4, and TSH by RIA because it is independent of TBG changes that result from pregnancy, birth-control pills, and estrogen replacement, is not spuriously elevated by the levothyroxine treatment itself, and is the only test that detects both subclinical hypothyroidism and subclinical hyperthyroidism. Additional serum tests are not usually necessary but have advantages under special circumstances. Once the optimal replacement dose is determined, monitoring can be done yearly or even bi-yearly, depending on the adequacy of patient education and patient compliance. .A Nordyke RA; Gilbert FI Jr. .I 274735 .U 91005115 .S Compr Ther 9101; 16(7):3-7 .M Human; Hyperthyroidism/DI; Hypothyroidism/DI; Levothyroxine/TU; Thyroid Function Tests/*; Thyrotropin/*AN; Thyroxine/AN. .T Diagnosis of thyroid dysfunction in ambulatory patients: primacy of the supersensitive thyroid-stimulating hormone assay. .P JOURNAL ARTICLE. .A Hamburger JI; Kaplan MM. .I 274736 .U 91005116 .S Compr Ther 9101; 16(7):33-40 .M Blood Glucose/*AN; Diabetes Mellitus/BL; Glucose Tolerance Test; Hemoglobin A, Glycosylated/*AN; Human. .T Correlation between glycemia and glycated hemoglobin. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .A Service FJ. .I 274737 .U 91005117 .S Compr Ther 9101; 16(7):41-8 .M Diabetes Mellitus/CO/DI/*PP; Diabetes Mellitus, Insulin-Dependent/CO/ME/PP; Diabetes Mellitus, Non-Insulin-Dependent/CO/ME/PP; Diabetic Nephropathies/PP; Glycosylation; Human; Hyperglycemia/ET/TH; Inositol/ME; Microcirculation/PP. .T Advances in the diagnosis and pathogenesis of diabetes mellitus and its complications. .P JOURNAL ARTICLE. .A Moller DE; Moses AC. .I 274738 .U 91005118 .S Compr Ther 9101; 16(7):49-55 .M Blood Glucose/AN; Diabetes Mellitus, Insulin-Dependent/BL/*DT; Drug Administration Schedule; Human; Insulin/*AD/TU. .T Modern management of the insulin-requiring patient. .P JOURNAL ARTICLE. .A Davidson MB. .I 274739 .U 91005119 .S Compr Ther 9101; 16(7):56-61 .M Atherosclerosis/ET; Diabetes Mellitus, Non-Insulin-Dependent/*/BL/CO/PP/TH; Diabetic Diet; Human; Hyperlipidemia/CO/TH; Hypertension/ET; Insulin/BL; Risk Factors. .T Update: non-insulin-dependent diabetes mellitus. .P JOURNAL ARTICLE. .A Sheehan JP. .I 274740 .U 91005120 .S Compr Ther 9101; 16(7):9-19 .M Adolescence; Amenorrhea/ET/PP; Child; Female; Gonadotropins, Pituitary/PH/SE; Growth/PH; Hormones/*SE; Human; Hypogonadism/ET/ME/PP; Male; Puberty/*PH; Puberty, Delayed/ME/PP/TH; Sex Hormones/PH/SE; Sex Maturation/PH. .T Adolescent endocrinology. .P JOURNAL ARTICLE. .A Wheeler MD. .I 274741 .U 91005186 .S Contact Dermatitis 9101; 23(2):103-10 .M Animal; Anthralin/*AA/*TO; Comparative Study; Dermatitis, Contact/*IM; Disease Models, Animal; Dose-Response Relationship, Immunologic; Female; Freund's Adjuvant/AD; Guinea Pigs; Injections, Intradermal; Irritants/*TO; Mice; Mice, Inbred BALB C; Patch Tests; Psoriasis/DT. .T Studies on the contact sensitizing activity of dithranol (anthralin) and 10-butyryl dithranol (butantrone). .P JOURNAL ARTICLE. .W The contact sensitizing activity of dithranol and butantrone (10-butyryl dithranol) was studied in 3 animal models: the guinea pig maximization test (GPMT), the closed patch test (CPT), and the mouse ear swelling test (MEST) in 2 different mouse strains. In the GPMT, both dithranol and, to a greater extent, butantrone showed sensitizing potential. Because butantrone was less irritant, the concentrations used were 10x higher than those of dithranol. In the CPT, only butantrone was slightly positive. In the MEST, with both CF-1 and Balb/c mice, dithranol caused less swelling of the test ear after challenge than butantrone. According to the evaluation criteria of the MEST, only butantrone caused sensitization in 50% of the CF-1 mice and in 40% of the Balb/c mice. Thus, the GPMT was the only test which indicated the minor contact sensitizing potential of dithranol. On the other hand, the 10-butyryl analogue of dithranol showed undoubtedly stronger contact sensitizing potential than the parent compound in all tests. Therefore, as compared to dithranol, an increased risk of sensitization should be considered. .A Viluksela M; Haasio K; Mannisto PT. .I 274742 .U 91005187 .S Contact Dermatitis 9101; 23(2):111-2 .M Dermatitis, Contact/*EP/ET; Dyes/*AE; Female; Human; Male; Occupational Dermatitis/*EP/ET; Patch Tests; Textiles/*. .T Prevalence of textile dye contact sensitization. .P JOURNAL ARTICLE. .A Balato N; Lembo G; Patruno C; Ayala F. .I 274743 .U 91005188 .S Contact Dermatitis 9101; 23(2):112-3 .M Administration, Cutaneous; Adult; Aged; Aged, 80 and over; Dermatitis Medicamentosa/*ET; Dermatitis, Contact/*ET; Female; Human; Ketoprofen/*AE; Male; Middle Age; Patch Tests. .T Contact allergy to ketoprofen: report of 7 cases. .P JOURNAL ARTICLE. .A Tosti A; Gaddoni G; Valeri F; Bardazzi F. .I 274744 .U 91005189 .S Contact Dermatitis 9101; 23(2):114 .M Adult; Case Report; Chronic Disease; Coffee/*AE; Dermatitis, Contact/*ET; Female; Food Handling/*; Hand Dermatoses/ET; Human; Occupational Dermatitis/*ET; Patch Tests. .T Occupational contact dermatitis due to coffee. .P JOURNAL ARTICLE. .A Piraccini BM; Bardazzi F; Vincenzi C; Tardio MP. .I 274745 .U 91005190 .S Contact Dermatitis 9101; 23(2):115 .M Aged; Case Report; Dermatitis Medicamentosa/*ET; Dermatitis, Contact/*ET; Female; Human; Leg Ulcer/DT; Pyridoxine/*AE. .T Contact allergy to vitamin B6. .P JOURNAL ARTICLE. .A Camarasa JG; Serra-Baldrich E; Lluch M. .I 274746 .U 91005191 .S Contact Dermatitis 9101; 23(2):116 .M Adult; Case Report; Hand Dermatoses/*CI; Human; Male; Middle Age; Mutagens/*AE; Occupational Dermatitis/*CI; Patch Tests; Photography; Recurrence; Thiazoles/*AE. .T 2 cases of occupational allergy to Kathon 886. .P JOURNAL ARTICLE. .A Brown R. .I 274747 .U 91005192 .S Contact Dermatitis 9101; 23(2):117-8 .M Acute Disease; Administration, Topical; Adult; Case Report; Cross Reactions; Dermatitis Medicamentosa/*ET; Dermatitis, Contact/*ET; Female; Hemorrhoids/DT; Human; Lidocaine/*AE; Patch Tests; Prilocaine/*AE. .T Contact sensitivity to lignocaine and prilocaine. .P JOURNAL ARTICLE. .A Black RJ; Dawson TA; Strang WC. .I 274748 .U 91005193 .S Contact Dermatitis 9101; 23(2):118-9 .M Adult; Air Pollutants, Occupational/*AE; Case Report; Cosmetics/AE; Dermatitis, Contact/*ET; Facial Dermatoses/CI; Female; Human; Kitasamycin/*AE; Leucomycins/*AE; Occupational Dermatitis/*CI; Patch Tests. .T Airborne allergic contact dermatitis from kitasamycin and midecamycin. .P JOURNAL ARTICLE. .A Dooms-Goossens A; Bedert R; Degreef H; Vandaele M. .I 274749 .U 91005194 .S Contact Dermatitis 9101; 23(2):119-20 .M Administration, Cutaneous; Atropine/IM; Backache/DT; Belladonna Alkaloids/*AE; Case Report; Dermatitis Medicamentosa/*ET; Dermatitis, Contact/*ET; Human; Male; Middle Age; Patch Tests. .T Belladonna plaster--not as bella as it seems. .P JOURNAL ARTICLE. .A Williams HC; du Vivier A. .I 274750 .U 91005195 .S Contact Dermatitis 9101; 23(2):120-1 .M Administration, Cutaneous; Anti-Inflammatory Agents, Steroidal/*AE; Dermatitis Medicamentosa/*ET; Eczema/*CI; Female; Human; Hydrocortisone/*AA/AE; Leg Ulcer/*CI; Patch Tests/*/MT. .T The significance of tixocortol-pivalate-positive patch tests in leg ulcer patients. .P JOURNAL ARTICLE. .A Wilkinson M; Cartwright P; English JS. .I 274751 .U 91005196 .S Contact Dermatitis 9101; 23(2):121-2 .M Adult; Dermatitis, Contact/*ET; Female; Human; Middle Age; Nickel/AE; Occupational Dermatitis/ET; Palladium/*AE; Patch Tests. .T Allergy to palladium. .P JOURNAL ARTICLE. .A Rebandel P; Rudzki E. .I 274752 .U 91005197 .S Contact Dermatitis 9101; 23(2):123-4 .M Case Report; Dermatitis, Contact/*ET; Dyes/*AE; Female; Hair Preparations/*AE; Human; Middle Age; Patch Tests; Psoriasis/*CI. .T Psoriasis-like contact dermatitis from a hair nitro dye. .P JOURNAL ARTICLE. .A Perno P; Lisi P. .I 274753 .U 91005198 .S Contact Dermatitis 9101; 23(2):124-5 .M Alopecia/TH; Case Report; Dermatitis, Contact/*ET; Dyes/*AE; Female; Hair/*; Human; Middle Age; Scalp Dermatoses/*CI. .T Contact dermatitis from disperse dyes in synthetic wigs [published erratum appears in Contact Dermatitis 1990 Nov;23(5):384] .P JOURNAL ARTICLE. .A Shehade SA; Beck MH. .I 274754 .U 91005199 .S Contact Dermatitis 9101; 23(2):125-6 .M Aged; Benzydamine/*AE; Case Report; Dermatitis Medicamentosa/*ET; Dermatitis, Contact/*ET; Facial Dermatoses/CI; Hand Dermatoses/CI; Human; Leg Ulcer/DT; Male; Patch Tests; Photosensitivity Disorders/*CI. .T Contact and photocontact dermatitis due to benzydamine hydrochloride. .P JOURNAL ARTICLE. .A Vincenzi C; Cameli N; Tardio M; Piraccini BM. .I 274755 .U 91005200 .S Contact Dermatitis 9101; 23(2):65-7 .M Adult; Aluminum/*AE; Case Report; Dermatitis Medicamentosa/*ET; Female; Human; Inflammation; Injections, Subcutaneous; Patch Tests; Viral Hepatitis Vaccines/AD/*AE. .T Inflammatory nodular reactions after hepatitis B vaccination due to aluminium sensitization. .P JOURNAL ARTICLE. .W In 2 patients, pruritic nodules appeared after revaccination against hepatitis B. Aluminium was found to be responsible for this side effect: contact allergy to aluminium was present in both patients, whereas controls were negative. .A Cosnes A; Flechet ML; Revuz J. .I 274756 .U 91005201 .S Contact Dermatitis 9101; 23(2):68-72 .M Administration, Cutaneous; Adolescence; Adult; Aged; Cosmetics/AE; Dermatitis Medicamentosa/ET/*IM; Dermatitis, Contact/ET/*IM; Ethanolamines/AE; Excipients/AD/*AE; Facial Dermatoses/ET/IM; Female; Hand Dermatoses/ET/IM; Human; Male; Middle Age; Patch Tests. .T Prevalence and sources of sensitization to emulsifiers: a clinical study. .P JOURNAL ARTICLE. .W 737 patients with suspected cosmetic- or medicament-related contact dermatitis were patch tested with 6 emulsifier agents: triethanolamine, cetyl stearyl alcohol, sorbitan sesquioleate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monooleate, and Amerchol L 101. 39 patients (5.3%) gave 1 or more positive patch tests to emulsifiers. A total of 54 positive reactions were found, 23 of which were clinically relevant, triethanolamine being the most frequent sensitizer. Patients with emulsifier sensitivity generally give a high prevalence of positive patch tests to other common ingredients of topical preparations, such as preservatives or active ingredients. Cosmetics and topical medicaments were detected as the source of sensitization in an equal number of patients. Patch tests with patients' own causative preparations were frequently negative. To avoid overlooking emulsifier sensitivity, it is advisable to test these compounds in patients with contact dermatitis that is possibly due to topical preparations, regardless of whether they have other clinically relevant positive reactions or whether patch tests with their own products are negative. .A Tosti A; Guerra L; Morelli R; Bardazzi F. .I 274757 .U 91005202 .S Contact Dermatitis 9101; 23(2):73-6 .M Administration, Cutaneous; Adult; Aged; Aged, 80 and over; Dermatitis Medicamentosa/IM; Dermatitis, Contact/*ET; Dietary Fats, Unsaturated/*AE; Eczema/*ET; Female; Human; Male; Middle Age; Occupational Dermatitis/*ET; Patch Tests; Plant Oils/AD/*AE/TU; Sweden. .T Olive oil as a cause of contact allergy in patients with venous eczema, and occupationally. .P JOURNAL ARTICLE. .W From 1985 to 1989, 13 cases of contact allergy to olive oil have been identified in the Departments of Dermatology of Kristianstad and Ostersund Hospitals. Known components of olive oil could not be proved to be the cause of the allergy. This high number of patients with contact allergy to olive oil and possible explanations are discussed. .A Malmkvist Padoan S; Pettersson A; Svensson A. .I 274758 .U 91005203 .S Contact Dermatitis 9101; 23(2):77-80 .M Adult; Aged; Agricultural Workers' Diseases/*ET; Carbamates/IM; Dermatitis, Contact/*ET; Female; Human; Irritants/AE; Male; Middle Age; Patch Tests; Pesticides/*AE. .T Contact sensitization by pesticides in farmers. .P JOURNAL ARTICLE. .W 30 farmers with contact dermatitis and 20 controls were patch tested with a series of locally used pesticides. Allergic reactions to 1 or more pesticides were seen in 11 patients but none of the controls. Carbamates (maneb, carbofuran, carbaryl) were the most frequent sensitizers (7 patients), followed by organophosphorus compounds like: malathion and oxydemton methyl (4 patients); 2,4-dichlorophenoxyacetic acid and fenvalerate (3 patients each); streptocycline (2 patients). Irritant reactions to captaf were seen in 4 patients, thiobencarb weedicide in 3, and organophosphorus compounds in 3. Pesticides should be patch tested in all farmers with contact dermatitis. .A Sharma VK; Kaur S. .I 274759 .U 91005204 .S Contact Dermatitis 9101; 23(2):81-9 .M Administration, Cutaneous; Animal; Clonidine/AD/*AE; Cyclophosphamide/AD/IM; Dermatitis, Contact/*ET/IM; Disease Models, Animal/*; Female; Freund's Adjuvant/AD; Guinea Pigs; Injections, Intradermal; Langerhans Cells/ME; Support, Non-U.S. Gov't; T-Lymphocytes/IM. .T Low allergenicity of clonidine impedes studies of sensitization mechanisms in guinea pig models. .P JOURNAL ARTICLE. .W During clinical trials, a clonidine transdermal device has been found to induce clonidine-specific allergic contact dermatitis in up to 25% of patients during a treatment period of 1 year. Using 3 different guinea pig strains, development was attempted of an experimental guinea pig model that would allow for in-depth studies into the mechanism of sensitization, and a possible role of transdermal device components. Transient low-level clonidine allergy could be obtained only in a minority of animals, with severe sensitization procedures departing from epicutaneous applications, combined with intradermal (adjuvant) FCA injections. Sensitization was not potentiated by additional booster procedures, including cyclophosphamide pretreatment, nor any of the putative cofactors (UV-treatments, C. parvum or acetaldehyde involvement) studied. These results suggest that the persistent skin contacts in man, with transdermal devices for sustained drug delivery, generate unique conditions favouring the development of allergic contact dermatitis, which are difficult to mimic in experimental animal models. Thus, clinical allergy may develop even to extremely weak sensitizing drugs that can be safely used orally, and escape most currently available predictive contact allergy animal models. Clinical studies remain unavoidable for studying factors that may reduce sensitization rates to more acceptable levels. .A Scheper RJ; von Blomberg BM; de Groot J; Goeptar AR; Lang M; Oostendorp RA; Bruynzeel DP; van Tol RG. .I 274760 .U 91005205 .S Contact Dermatitis 9101; 23(2):90-5 .M Animal; Cross Reactions/IM; Dermatitis, Contact/*IM; Female; Freund's Adjuvant/AD; Guinea Pigs; Injections, Intradermal; Resins/AD/*AE; Support, Non-U.S. Gov't; Tars/AD/*AE. .T Contact allergy due to colophony (VI). The sensitizing capacity of minor resin acids and 7 commercial modified-colophony products. .P JOURNAL ARTICLE. .W 3 minor resin acids and 7 commercial modified-colophony products of different origins were studied by experimental sensitization by means of a modified FCA method. All 3 resin acids were almost negative. The commercial products gave different results. While the maleic-modified product of Greek origin showed a strong sensitizing power, the fumaric-modified, terpene-phenol-modified and a disproportioned rosin were only moderate. A remarkable difference was obtained with the Swedish and Finnish tall oil rosins, which, in contrast to the previously studied French product, exhibited only a weak sensitizing capacity. .A Hausen BM; Hessling C. .I 274761 .U 91005206 .S Contact Dermatitis 9101; 23(2):96-102 .M Acrylic Resins/*AE; Adult; Dermatitis, Contact/ET/*PA; Female; Hand Dermatoses/CI/PA; Human; Male; Methacrylates/*AE; Microscopy, Electron; Occupational Dermatitis/CI/*PA; Patch Tests; Protective Clothing; Skin/UL; Support, Non-U.S. Gov't. .T Contact dermatitis from acrylate and methacrylate compounds in Lowicryl embedding media for electron microscopy. .P JOURNAL ARTICLE. .W This report is about occupational contact dermatitis found in 3 out of 6 workers of a chemistry laboratory using Lowicryl embedding media, which contain (meth)acrylate monomer mixtures of known composition. The notation (meth)acrylates is used to refer to both acrylates and methacrylates. (Meth)acrylate monomers will polymerize in the absence of oxygen when induced by metal ions, peroxides, heat or ultraviolet light. The monomers are of low viscosity and remain in the liquid state at temperatures far below 0 degree C. The volatile compounds, some of which exhibit a most pungent odour, have a tendency to penetrate all tissue and to permeate into the finest fissures, a property which makes them suitable as sealants, glues, embedding material, etc. This and their toxicity may represent a danger to the health of individuals who need to work with them, especially if no precautions are taken. We show with patch testing that one patient reacted strongly to the compound 2-hydroxyethyl acrylate at the dilutions tested (0.5 and 1% v/v), but not at all to 10 other (meth)acrylates. In the same test, 3 volunteer controls were negative to 2-hydroxyethyl acrylate. We demonstrate that at maximum working concentration, 2-hydroxyethyl acrylate penetrates both latex and vinyl gloves and elicits irritant/allergic reactions on the patient and irritant reactions on a control. Finally, we discuss the necessary protective measures. .A Tobler M; Wuthrich B; Freiburghaus AU. .I 274762 .U 91005258 .S Crit Care Med 9101; 18(10):1055-60 .M Adolescence; Adult; Aged; Cardiac Output; Child; Echocardiography; Female; Hemodynamics/*; Human; Middle Age; Pulmonary Wedge Pressure; Septicemia/*CO; Shock, Cardiogenic/ET/*PP/US; Stroke Volume; Support, Non-U.S. Gov't. .T Sepsis-related cardiogenic shock. .P JOURNAL ARTICLE. .W To further define cardiovascular abnormalities in patients with septic shock, serial conventional hemodynamic measurements combined with two-dimensional echocardiographic studies were performed at the bedside in 21 patients admitted for an acute episode of sepsis-related circulatory failure. Measurements obtained during the first hours of hospitalization revealed a group of six patients (group 1) with markedly depressed left ventricular function, as evidenced by a low cardiac index (CI) (2.2 +/- 0.8 L/min.m2), reduced left ventricular ejection fraction (LVEF) (21 +/- 8%), and an increased arterial-venous oxygen content difference. Right ventricular systolic function was also severely depressed. These patients were characterized as having sepsis-related cardiogenic shock secondary to profound myocardial depression, which was reversible within 24 to 48 h with inotropic support. The 15 remaining patients (group 2) exhibited an initially increased CI (4.9 +/- 1.8 L/min.m2), with a low systemic vascular resistance. In group 2, LVEF remained within the normal range despite abnormally low peripheral vascular resistance. This finding would suggest the presence of slight to moderate depression of left ventricular systolic function. All patients in this series had a normal left ventricular end-diastolic volume, whether profound myocardial depression was present or not. .A Jardin F; Brun-Ney D; Auvert B; Beauchet A; Bourdarias JP. .I 274763 .U 91005259 .S Crit Care Med 9101; 18(10):1061-5 .M Adult; Aged; Blood Pressure; Drug Therapy, Computer-Assisted/*ST; Evaluation Studies; Female; Heart Surgery/*/AE; Human; Hypertension/*DT/ET/NU; Infusion Pumps/*ST; Male; Middle Age; Nitroprusside/*AD/TU; Postoperative Complications/*DT. .T Use of a computerized closed-loop sodium nitroprusside titration system for antihypertensive treatment after open heart surgery. .P JOURNAL ARTICLE. .W This study evaluates the clinical applicability of administering sodium nitroprusside by a closed-loop titration system compared with a manually adjusted system. The mean arterial pressure (MAP) was registered every 10 and 30 sec during the first 150 min after open heart surgery in 20 patients (group 1: computer regulation) and in ten patients (group 2: manual regulation). The results (16,343 and 2,912 data points in groups 1 and 2, respectively), were then analyzed in four time frames and five pressure ranges to indicate clinical efficacy. Sixty percent of the measured MAP in both groups was within the desired +/- 10% during the first 10 min. Thereafter until the end of observation, the MAP was maintained within +/- 10% of the desired set-point 90% of the time in group 1 vs. 60% of the time in group 2. One percent and 11% of data points were +/- 20% from the set-point in groups 1 and 2, respectively (p less than .05, chi-square test). The computer-assisted therapy provided better control of MAP, was safe to use, and helped to reduce nursing demands. .A Bednarski P; Siclari F; Voigt A; Demertzis S; Lau G. .I 274764 .U 91005260 .S Crit Care Med 9101; 18(10):1066-9 .M Adolescence; Blood Gas Analysis/IS/*ST; Body Temperature; Child; Child, Preschool; Comparative Study; Heart Rate; Heart Surgery/*; Human; Hypothermia, Induced/*; Infant; Monitoring, Physiologic/MT/ST; Oximetry/IS/*ST; Postoperative Period; Reproducibility of Results. .T Oximetry in children recovering from deep hypothermia for cardiac surgery. .P JOURNAL ARTICLE. .W Although pulse oximetry is a potentially useful diagnostic tool in the treatment of children after major open heart surgery, there are concerns regarding its reliability for measuring oxygen saturation (SaO2) in hypothermic or low perfusion states. To test pulse oximeter reliability in children under these conditions, our study compared 187 SaO2 pulse oximeter readings (Biox 3700) with simultaneous hemoximeter (OSM2, Radiometer) readings from 56 children rewarming after open heart surgery. Ages ranged from 4 months to 18 yr; temperatures ranged from 23.5 degrees to 38 degrees C (toe) and 31.3 degrees to 40.8 degrees C (core). The mean pulse oximeter SaO2 reading was 94.90% (SD 7.18, range 54% to 100%), mean hemoximeter reading was 96.07% (SD 7.06; minimum 54%; maximum 100%). The correlation between the readings was high (r = .88, p less than .005), and was not affected by low core temperature. When oximeter and cardiac monitor pulse rates coincided, the oximeter SaO2 value was within +/- 5% (p less than .05). We conclude that the Biox 3700 oximeter is reliable for noninvasive SaO2 monitoring in mild to moderately hypothermic children after open heart surgery, particularly when oximeter and cardiac heart rates coincide. Further studies are needed to confirm our findings in children with core temperatures less than 31.3 degrees C, and when other oximeters are used. .A Macnab AJ; Baker-Brown G; Anderson EE. .I 274765 .U 91005261 .S Crit Care Med 9101; 18(10):1070-2 .M Airway Resistance; Flowmeters/*ST; Human; Infant, Newborn; Lung Compliance/*; Monitoring, Physiologic/IS/MT/ST; Reproducibility of Results; Respiration, Artificial/*; Temperature; Tidal Volume/*. .T Measuring on-line compliance in ventilated infants using hot wire anemometry. .P JOURNAL ARTICLE. .W We investigated the validity of using tidal volume (VT) as measured by the neonatal volume monitor (NVM) to derive respiratory compliance. The NVM is a noninvasive device that measures VT by hot wire anemometry. The quotient of VT and the inflation pressure amplitude from the mechanical ventilator provided a measure of respiratory compliance. This was validated against the single breath occlusion technique in 15 infants (birth weight 0.9 to 4.4 kg). To ensure fully passive expiration, only paralyzed or sedated patients were studied. Only 12 of the 15 infants were analyzed because of limitations in the single breath technique. In three infants the flow-volume curves obtained were alinear, indicating inhomogeneity. In the 12 infants with acceptable single breath data, agreement between the two methods was excellent. Using the expired volume, r2 was .99. We conclude that the NVM can be used to obtain valid estimates of respiratory compliance on-line in intubated infants. .A Baboolal R; Kirpalani H. .I 274766 .U 91005262 .S Crit Care Med 9101; 18(10):1073-9 .M Adolescence; Adult; Aged; Asepsis/MT/*ST; Catheters, Indwelling/*; Clinical Protocols/*ST; Critical Care; Equipment Contamination/*; Human; Incidence; Middle Age; Postoperative Care; Prospective Studies; Risk Factors; Septicemia/EP/*ET/MI; Severity of Illness Index. .T Catheter-related sepsis: prospective, randomized study of three methods of long-term catheter maintenance. .P CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL. .W We studied the infectious risk of different methods of managing vascular catheters during long-term use. Consecutive surgical ICU patients requiring triple lumen catheters, pulmonary artery catheters, or arterial catheters for greater than 7 days were prospectively randomized to one of three management groups: a) percutaneous (PERC) puncture with every 7-day catheter change at a new site, b) no weekly change (NWC) with a new site when changed, or c) guidewire exchange (GWX) with every 7-day catheter change at the same site. In all groups, a catheter change was mandatory for a positive blood culture, skin site infection, or sepsis without a likely source. Cultures were obtained when clinically indicated and at the time of every catheter change. Catheter-related sepsis (CRS) was defined as a positive blood culture and catheter culture with the same organism. A total of 112 patients met evaluation criteria. There were no intergroup differences in age, primary diagnosis, severity of injury or illness, number of study days, number of protocol violations, route of catheterization, number of catheters present/patient day, catheter sepsis rate, or bacteremia rate. The NWC group demonstrated an increased number of days/catheter, fewer catheter/subcutaneous tract segment cultures/patient, and a reduced incidence of catheter tip colonization. These results occurred in a setting where the number of CRS episodes/patient was 0.17 for GWX, 0.22 for PERC, and 0.16 for NWC. We conclude that there is no difference in infectious risk between these three methods of long-term catheter management. The method with the least complications and expense should be used.(ABSTRACT TRUNCATED AT 250 WORDS) .A Eyer S; Brummitt C; Crossley K; Siegel R; Cerra F. .I 274767 .U 91005263 .S Crit Care Med 9101; 18(10):1080-6 .M Adolescence; Adult; Aged; Airway Resistance/*; Female; Human; Lung Compliance/*; Lung Volume Measurements; Male; Middle Age; Pulmonary Gas Exchange; Respiration, Artificial/*; Respiratory Airflow/*; Respiratory Dead Space; Respiratory Distress Syndrome, Adult/*PP/TH; Respiratory Mechanics/*; Support, Non-U.S. Gov't. .T Flow and volume dependence of respiratory system mechanics during constant flow ventilation in normal subjects and in adult respiratory distress syndrome. .P JOURNAL ARTICLE. .W Seven control subjects and seven patients with adult respiratory distress syndrome (ARDS) were artificially ventilated and flow, volume, and tracheal pressure were monitored. Respiratory system resistance (Rrs,max) was partitioned into its homogeneous (Rrs,min) and uneven (Rrs,u) components. Respiratory system elastance (Ers) was also measured. In both groups Ers did not vary with different inspiratory flows and volumes, but was significantly higher in ARDS. With increasing volume (isoflow maneuvers), Rrs,max and Rrs,u increased but Rrs,min remained unaltered in ARDS. In control patients, however, resistances did not vary but Rrs,max and Rrs,u were smaller and Rrs,min equaled their corresponding values in ARDS. Hence, stress relaxation seems to be increased in ARDS. During isovolume maneuvers Rrs,max and Rrs,u decreased with increasing flows (both groups), although they were significantly higher in ARDS. Rrs,min was not modified by different flows and was similar in both groups. Thus, pendelluft is also increased in ARDS. In conclusion, the mechanical profile of ARDS is characterized by increased Ers and Rrs,max, the latter being secondary to augmented mechanical unevenness within the system. .A Auler JO Jr; Saldiva PH; Martins MA; Carvalho CR; Negri EM; Hoelz C; Zin WA. .I 274768 .U 91005264 .S Crit Care Med 9101; 18(10):1087-91 .M Blood Gas Analysis; Blood Transfusion/MT/*ST; Child; Child, Preschool; Female; Hematocrit; Hemodynamics; Hemoglobins/AN; Human; Infant; Male; Oxygen Consumption/*; Prospective Studies; Shock, Septic/BL/PP/*TH. .T Effect of blood transfusion on oxygen consumption in pediatric septic shock. .P JOURNAL ARTICLE. .W Treatment plans for pediatric septic shock advocate increasing oxygen consumption (VO2). Recent studies in septic shock indicate that improving oxygen delivery (DO2) by increasing blood flow will increase VO2. We prospectively examined the effect on VO2 of improving DO2 by increasing oxygen content (CO2) with blood transfusion in eight hemodynamically stable septic shock patients. Transfusion consisted of 8 to 10 ml/kg of packed RBC over 1 to 2 h. Hemodynamic and oxygen transport measurements were obtained before and after blood transfusion. Transfusion significantly (p less than .05) increased Hgb and Hct from 10.2 +/- 0.8 g/dl and 30 +/- 2% to 13.2 +/- 1.4 g/dl and 39 +/- 4%, respectively (mean +/- SD). DO2 significantly (p less than .05) increased after transfusion (599 +/- 65 to 818 +/- 189 ml/min.m2), but VO2 did not change (166 +/- 68 to 176 +/- 74 ml/min.m2; NS). In pediatric septic shock patients, increasing CO2 by blood transfusion may not increase VO2. .A Mink RB; Pollack MM. .I 274769 .U 91005265 .S Crit Care Med 9101; 18(10):1092-5 .M Adult; Aged; Aged, 80 and over; Aluminum Hydroxide/TU; Antacids/TU; Aspiration; Comparative Study; Drug Combinations; Evaluation Studies; Female; Gastric Acidity Determination/*IS; Human; Hydrogen-Ion Concentration; Intensive Care Units/*; Intubation, Gastrointestinal/*; Magnesium Hydroxide/TU; Male; Microelectrodes/*ST; Middle Age; Peptic Ulcer/*DI/DT/ET; Prospective Studies; Ranitidine/TU; Stress, Psychological/*CO. .T Prospective trial comparing a combination pH probe-nasogastric tube with aspirated gastric pH in intensive care unit patients. .P CLINICAL TRIAL; JOURNAL ARTICLE. .W Upper GI bleeding related to stress ulcer syndrome is estimated to affect as much as 15% of patients in an ICU. Since the occurrence of bleeding after ICU admission may be associated with increased morbidity and mortality, many efforts have been directed at defining optimal therapy for stress ulcer prophylaxis. Titration of intragastric pH with antacids or iv doses of H2-receptor antagonists may prevent stress ulcer bleeding in high-risk ICU patients. We evaluated a recently developed pH probe incorporated into an NG tube and compared it with aspiration of gastric contents using pH paper as a means to monitor pH in 22 surgical ICU patients. Regression analysis comparing the intragastric probe pH values with the aspirated pH values showed a good correlation between the two methods (r = .71). This new technique for intragastric pH measurement appears technically simple and clinically applicable for use on patients at risk for stress ulcer bleeding. It may be more accurate than pH paper in patients receiving antacids. .A Eisenberg PG; Cort D; Zuckerman GR. .I 274770 .U 91005267 .S Crit Care Med 9101; 18(10):1102-6 .M Anesthesia/*; Calibration; Functional Residual Capacity/*; High-Frequency Jet Ventilation/*; Human; Intermittent Positive-Pressure Ventilation/*; Reproducibility of Results; Respiratory Dead Space; Respiratory Mechanics/*; Spirometry/*ST; Tidal Volume/*. .T Pulmonary volume measurements during high-frequency jet ventilation in anesthetized man. .P JOURNAL ARTICLE. .W To assess the validity of indirect spirometry during conventional intermittent positive-pressure ventilation (IPPV) and high-frequency jet ventilation (HFJV), we measured changes in functional residual capacity (delta FRC) and tidal volume (VT) with two external strain gauges in eight sedated and paralyzed patients. The thoracic and abdominal gauges were calibrated simultaneously in quasi-static and dynamic conditions. The delta FRC measured during HFJV (1 to 5 Hz) and the VT measured during IPPV (0.25 Hz) were found to be equivalent by the two gauges in most patients (r = .90 and r = .99, respectively), but no correlation was found between the VT values inferred by each gauge in HFJV (r = .54). During HFJV, spectral analysis of the gauge signals showed important damping of the abdominal motion (AB) and an amplification of the thoracic displacements (RC) in four patients when measurements were taken at greater than 3 Hz. We conclude that, provided the partition of the volume between AB and RC remains constant, indirect spirometry may measure VT in IPPV and delta FRC in HFJV, but it fails to measure VT accurately during HFJV. .A Beydon L; Bourgain JL; Benlabed M; Bourgain L. .I 274771 .U 91005268 .S Crit Care Med 9101; 18(10):1107-10 .M Cardiac Output, Low/*DT/ET/PP; Cardiopulmonary Bypass/*AE; Dobutamine/ME/*PD/TU; Hemodynamics/*DE; Oxygen Consumption/*DE; Pulmonary Circulation/DE; Vascular Resistance/DE. .T Hemodynamic and metabolic effects of dobutamine in 18 patients after open heart surgery. .P JOURNAL ARTICLE. .W Low cardiac output syndrome frequently follows cardiopulmonary bypass (CPB) surgery. In the present study, we used dobutamine to increase cardiac index (CI) and oxygen delivery (DO2) in 18 patients after open heart surgery. Using increasing doses of dobutamine up to 10 micrograms/kg.min-1, we observed statistically significant (p less than .01) increases in mean CI (2.50 +/- 0.10 to 3.56 +/- 0.18 L/min.m2) and in mean heart rate (HR) (83 +/- 3 to 105 +/- 3 beat/min). Mean systemic vascular resistance index decreased significantly (p less than .01) in all patients (2271 +/- 101 to 1648 +/- 83 dyne.sec/cm5.m2). Pulmonary vascular resistance index did not change in the ten coronary artery bypass graft patients, but decreased significantly (p less than .01) in the eight valve replacement patients (561 +/- 98 to 421 +/- 79 dyne.sec/cm5.m2). Mean DO2 increased in all patients, although there was no concomitant increase in oxygen consumption (VO2) in four patients. We observed a significant (p less than .01) increase in mean VO2 in the remaining 14 patients (110 +/- 6 to 148 +/- 12 ml/min.m2), in spite of significant decreases in PaO2 and increases in right-to-left intrapulmonary shunting. Although increases in HR and ventricular arrhythmias may limit its use, dobutamine increases CI and DO2 in patients after CPB. In the present study, dobutamine's varying metabolic effect exemplifies the need for close monitoring of hemodynamic and metabolic variables when using vasoactive drugs in the postoperative period. .A Schwenzer KJ; Kopel RF. .I 274772 .U 91005269 .S Crit Care Med 9101; 18(10):1111-8 .M Female; Human; Intensive Care Units/*; Male; Models, Statistical; Mortality/*; Outcome and Process Assessment (Health Care)/*ST; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Factors; ROC Curve; Severity of Illness Index/*; Support, Non-U.S. Gov't; Survival Rate. .T Outcome prediction models on admission in a medical intensive care unit: do they predict individual outcome? .P JOURNAL ARTICLE. .W Prospectively acquired data from 941 patients staying greater than 24 h in a medical ICU were analyzed to determine the relevance of scoring on ICU admission by the following methods of outcome prediction: Acute Physiology and Chronic Health Evaluation (APACHE II), Simplified Acute Physiology Score (SAPS), and Mortality Prediction Model (MPM). Analysis was performed separately for all patients (group A) and for a subsample (group B), obtained by excluding coronary care patients. Calculation of risk and classification of patients were carried out as recommended in the literature for MPM, APACHE II, and SAPS. In group A, sensitivities (correct prediction of hospital mortality) were 44.7%, 51.1%, and 21.2% and specificities (correct prediction of survival) were 84.5%, 85.4%, and 96.8%, respectively; overall correct classification rates were 73.3%, 75.8%, and 75.6%. In group B, sensitivities were slightly higher, but total correct classification rates did not reach group A levels. Goodness-of-fit testing showed low levels of fit for all methods in both groups. Application of APACHE II to diagnostic subgroups, using disease-adapted risk calculations, revealed marked inconsistencies between the estimated risk and the observed mortality. We conclude that the estimation of risk on admission by the three methods investigated might be helpful for global comparisons of ICU populations, although the lack of disease specificity reduces their applicability for severity grading of a given illness. The inaccuracy of these methods makes them ineffective for predicting individual outcome; thus, they provide little advantage in clinical decision-making. .A Schafer JH; Maurer A; Jochimsen F; Emde C; Wegscheider K; Arntz HR; Heitz J; Krell-Schroeder B; Distler A. .I 274773 .U 91005270 .S Crit Care Med 9101; 18(10):1119-23 .M Adult; Aged; Aircraft/*; Emergency Medical Services/*; Female; Human; Male; Middle Age; Mortality/*; Predictive Value of Tests/*; Severity of Illness Index/*; Support, Non-U.S. Gov't; Transportation of Patients/*. .T Rapid acute physiology scoring in transport systems. .P CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY. .W A multi-institutional study was undertaken to define the predictive power for mortality of the Rapid Acute Physiology Score (RAPS) in a large and diverse group of transported patients. RAPS is a truncated version of the Acute Physiology and Chronic Health Evaluation (APACHE II) score that uses definitions and weighting consistent with APACHE II, but is modified to provide a consistent score just before transport, just after transport, and to use the most deranged (worst) physiologic values during the initial 4 h after arrival at the receiving hospital. During an 8-month period, 1,927 patients transported by six helicopter emergency medical service programs were studied. Over 97% (1,881) of the patients had RAPS obtained before and after transport to the receiving hospital and 92.6% (1,785) had APACHE II scoring completed after hospital admission. Receiver operating curves demonstrate similar predictive power for RAPS and APACHE II (both based on the most deranged physiologic values during the initial 24 h after admission). Before- and after-transport RAPS were also highly predictive of mortality. RAPS appears to be a reliable and highly predictive measure of patient severity/physiologic stability before and after transport to critical care. .A Rhee KJ; Mackenzie JR; Burney RE; Willits NH; O'Malley RJ; Reid N; Schwabe D; Storer DL; Weber R. .I 274774 .U 91005271 .S Crit Care Med 9101; 18(10):1124-8 .M Atropine/TU; Case Report; Child, Preschool; Clonidine/*PO; Consciousness; Critical Care/*; Dopamine/TU; Dose-Response Relationship, Drug; Female; Fluid Therapy; Human; Infant; Length of Stay; Male; Naloxone/TU; Poisoning/DT/PP/*TH; Resuscitation; Retrospective Studies. .T Critical care for clonidine poisoning in toddlers. .P JOURNAL ARTICLE. .W Clonidine may be a source of serious toxicity when ingested by toddlers. We describe 11 cases of clonidine ingestion by toddlers (mean dose 0.15 mg/kg; range 0.01 to 0.57). The source of the clonidine was a grand-parent in six of 11 cases. Symptoms included altered level of consciousness (n = 11), miosis (n = 5), bradycardia (n = 8), hypotension (n = 5), apnea and respiratory depression (n = 6), hypothermia (n = 5) and hypertension (n = 3). Therapeutic interventions included naloxone (n = 8) and atropine (n = 4), dopamine (n = 1), fluid resuscitation (n = 4), and endotracheal intubation (n = 1). There were no deaths. Symptoms of clonidine ingestion were typically mild if the dose ingested was less than 0.01 mg/kg, while bradycardia and hypotension occurred usually with doses of greater than 0.01 mg/kg. Apnea and respiratory depression were common when the dose exceeded 0.02 mg/kg. More effective measures are needed to prevent these potentially serious intoxications. .A Fiser DH; Moss MM; Walker W. .I 274775 .U 91005272 .S Crit Care Med 9101; 18(10):1129-33 .M Animal; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Hemodynamics/DE; Hypertension, Pulmonary/*DT/ET/PP; Infusions, Intravenous; Prostaglandins E/AD/*PD/TU; Pulmonary Circulation/*DE; Pulmonary Embolism/*CO; Pulmonary Gas Exchange/DE; Pulmonary Wedge Pressure/DE; Support, Non-U.S. Gov't; Vascular Resistance/*DE. .T Role of prostaglandin E1 in reducing pulmonary vascular resistance in an experimental model of acute lung injury. .P JOURNAL ARTICLE. .W To determine the role and efficacy of prostaglandin E1 (PGE1) on the cardiopulmonary derangements induced by glass bead embolism, two studies were performed. In the first study, a dose response of PGE1 was tested in six animals that were first embolized with sufficient glass beads to double the pulmonary artery pressure (PAP). This study demonstrated that PGE1 reduced PAP and cardiac output by a preload-mediated mechanism, as evidenced by a reduction in the right ventricular (RV) end-diastolic segment length, at doses of 15 and 30 ng/kg.min. The second study was performed in two groups of animals, the control group (n = 6), and the treated group (n = 6), which were given PGE1 at 15 ng/kg.min after the PAP had been doubled by glass bead embolism. RV preload was kept constant. This study demonstrated that there was no difference in pulmonary vascular resistance between either the treated group or the control group. There were no other significant differences between the two groups. The results of both of these studies suggest that there is little afterload reducing effect of PGE1 in this model and at these dose ranges. Part of the mechanism of PGE1 that improves pulmonary edema and gas exchange may be the reduction of filtration surface area and hydrostatic pressures in the lungs. .A Dervin G; Calvin JE Jr. .I 274776 .U 91005273 .S Crit Care Med 9101; 18(10):1134-7 .M Animal; Cardiopulmonary Bypass/*; Clinical Protocols; Dogs; Epinephrine/*BL; Heart Arrest/*BL/PP/TH; Hemodynamics; Norepinephrine/BL; Resuscitation/*. .T Plasma epinephrine levels in resuscitation with cardiopulmonary bypass. .P JOURNAL ARTICLE. .W Since the highest plasma epinephrine levels have been recorded during resuscitation, we evaluated the isolated effect of cardiac arrest upon adrenomedullary secretion. We determined plasma epinephrine in dogs resuscitated with cardiopulmonary bypass (CPB) after cardiac arrest periods of 12 (CPB-12; n = 4) or 16 min (CPB-16; n = 5). Through 2 h of CPB and the following 6 h of critical care, there was no difference between CPB-12 and CPB-16 regarding most cardiopulmonary functional variables. Plasma epinephrine was markedly elevated immediately after initiation of CPB (p less than .01 at 1 min CPB vs. basal) and returned rapidly to basal concentrations. Comparison of plasma epinephrine levels between CPB and standard CPR groups showed that responses to cardiac arrest were similar (p greater than .05 at 1 min CPB vs. 11.5 min CPR). We conclude that cardiac arrest is the main or sole determinant of the plasma epinephrine elevation of resuscitation. .A Wortsman J; Nowak RM; Martin GB; Paradis NA; Cryer PE. .I 274777 .U 91005274 .S Crit Care Med 9101; 18(10):1138-41 .M Blood Transfusion/IS/MT/*ST; Emergencies; Heating/IS/MT/*ST; Hemoglobins/AN; Hemorrhage/*TH; Nephelometry and Turbidimetry; Osmotic Fragility; Potassium/AN; Quality Control; Sodium Chloride/TU; Thermography; Tissue Preservation/MT/ST. .T Rapid admixture blood warming: technical advances. .P JOURNAL ARTICLE. .W The technique of rapid admixture blood warming of cold erythrocyte units is designed to warm erythrocyte units rapidly (less than 30 sec) while simultaneously providing saline for dilution. However, questions have been raised about the recommended use of a standard 250-ml bolus of 70 degrees C admixture saline, the uniformity and speed of blood unit warming, the difficulties inherent in keeping saline bags at 70 degrees C, and the safety of the methodology. To answer these questions, a series of tests were performed and modifications of the technique were introduced. The mean weight of 1000 successive units of erythrocytes for adult infusion was 305 g (range 220 to 410). The maximum temperature was 44 degrees C, using an internal temperature probe (1-cm temperature gradations; 2-sec recording intervals) when the smallest unit was admixed with a 250 ml 70 degrees C saline bolus; the largest unit had a minimum temperature of 30 degrees C. Plasma Hgb, osmotic fragility, and K of the minimum size erythrocyte unit showed no significant deviation from its control. Both thermographic photographs and the internal temperature recordings of the erythrocyte units demonstrated that solely due to fluid turbulence, uniform mixing occurs within approximately 30 sec of beginning the admixture process. Inverting the blood units caused a thermal layering of fluids and an unacceptable maximum blood temperature of 50 degrees C. There was no difference between the mixing time or efficacy in the presence of standard or large-bore iv tubing or additional in-line filters. Volumes of the 250-ml saline bags for admixture decreased markedly with deviations in electrolyte composition after greater than 2 wk at 70 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) .A Iserson KV; Knauf MA; Anhalt D. .I 274778 .U 91005275 .S Crit Care Med 9101; 18(10):1142-5 .M Animal; Blood Pressure Determination/ST; Blood Pressure Monitors/*ST; Blood Volume/*; Catheterization, Central Venous; Comparative Study; Disease Models, Animal; Dogs; Evaluation Studies; Extracellular Space; Hemodynamics; Pulmonary Wedge Pressure; Water-Electrolyte Imbalance/DI/EP/*PP. .T Peripheral venous monitoring with acute blood volume alteration: cuff-occluded rate of rise of peripheral venous pressure. .P JOURNAL ARTICLE. .W We investigated the use of a new peripheral hemodynamic monitoring technique, the cuff-occluded rate of rise of peripheral venous pressure (CORRP), in the assessment of volume status in fluid overload. Seven adult mongrel dogs were given a general anesthetic, and monitoring lines were inserted. The animals were then subjected to an incremental volume overload of approximately 13% of estimated initial blood volume at 5-min intervals until a total volume infusion nearly equal to the animal's initial blood volume was reached. Comparison of the various monitoring techniques (e.g., cardiac output, CVP, systemic BP, pulmonary wedge pressure) demonstrated that the peripheral measurement of CORRP had better correlation with known administered volume (r = .96) than any of the other variables. The sensitivity of each of the variables in assessing small amounts of volume overload was also studied. The volume of crystalloid infusion necessary to cause a clinically significant change (defined as greater than 2 SD above the baseline mean) was compared for each of the monitoring variables. CORRP was equivalent to the other variables in sensing early volume overload. In summary, in the anesthetized animal model CORRP appears to be a sensitive, minimally invasive method of assessing volume status in acute volume overload. The efficacy of CORRP in a canine hemorrhagic shock and reperfusion model had previously been demonstrated. This technique could be clinically applicable in situations such as trauma with hemorrhagic shock, intraoperative volume changes, and in the assessment of intravascular volume after resuscitation. .A Snyder CL; Saltzman D; Happe J; Eggen MA; Ferrell KL; Leonard AS. .I 274779 .U 91005276 .S Crit Care Med 9101; 18(10):1146-51 .M Animal; Blood Flow Velocity/*; Blood Viscosity; Brain/BS; Capillaries/*; Dogs; Female; Heart Arrest/BL/*PP/TH; Hemodilution/*ST; Hemodynamics/*; Intra-Aortic Balloon Pumping; Male; Pancreas/BS; Resuscitation/MT; Stomach/BS; Thyroid Gland/BS. .T Effect of hemodilution on capillary and arteriolovenous shunt flow in organs after cardiac arrest in dogs. .P JOURNAL ARTICLE. .W The purpose of this study was to observe the changes in capillary and arteriolovenous shunting blood flow after cardiac arrest and subsequent resuscitation by venous return occlusion produced by inflation of an intra-atrial balloon and cross-clamping of the ascending aorta, and to determine how hemodilution might modify such changes. Organ capillary blood flow and the fractional distribution of cardiac output were measured by the microsphere (9-microns diameter) trapping method in dogs. Simultaneously, the arteriolovenous shunt rate was measured by continuous collection of venous blood drained at 4.8 ml.min-1 for 2 min from the brain, kidney, liver, splanchnic organs, skeletal muscle of the pelvic limb, and all of the systemic circulatory organs. The capillary blood flow of the brain, thyroid gland, pancreas, and stomach decreased after circulatory arrest in five nonhemodiluted dogs (group C); arteriolovenous shunt rate was unchanged after circulatory arrest in this group. However, with hemodilution, which was induced either before (pre group, n = 5) or after (post group, n = 5) circulatory arrest, no change occurred in the shunt rate in any of the organs, with the exception of an increase in the systemic arteriolovenous shunt rate in the pre group. Capillary blood flow was maintained at almost the same level as before circulatory arrest in the pre group, but increased significantly in several organs of the post group. The data indicated that hemodilution might be effective for prevention of organ ischemia after cardiac arrest. .A Yano H; Takaori M. .I 274780 .U 91005277 .S Crit Care Med 9101; 18(10):1152-7 .M Animal; Blood Flow Velocity; Blood Gas Analysis; Bronchial Arteries/*PP; Evaluation Studies; Female; Hemodynamics; Positive-Pressure Respiration/*ST; Pulmonary Circulation/*; Sheep; Smoke Inhalation Injury/BL/*PP/TH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Vascular Resistance. .T Bronchial blood flow reduction with positive end-expiratory pressure after acute lung injury in sheep. .P JOURNAL ARTICLE. .W Smoke inhalation increases bronchial blood flow (Qbr) and produces edema of the airway system. This study investigates whether the increased Qbr seen 24 h after inhalation injury can be affected by mechanical ventilation with PEEP (5, 10, 15 cm H2O). Sheep (n = 8) previously prepared with cardiopulmonary catheters and ultrasonic transit time flow probes mounted around their bronchial arteries were insufflated with four sets of 12 breaths each of cotton smoke. Different levels of PEEP were added to the mechanical ventilation 24 h after injury; each PEEP level was applied for 45 min. There were significant increases in Qbr and lung lymph flow (QL) associated with a marked decrease in bronchial vascular resistance (BVR) 24 h after injury. However, no change was observed in mean arterial pressure (MAP) or cardiac index (CI). There was a substantial reduction in PaO2/FIO2 (P/F), which indicated a deterioration in arterial oxygenation. The application of varying levels of PEEP decreased Qbr (p less than .05) while BVR increased (p less than .05), but QL and P/F did not. CI and MAP were recorded. After removal of PEEP, none of the cardiopulmonary variables were significantly different from their postsmoke control values. These findings suggest that mechanical ventilation with PEEP markedly decreases the smoke-induced hyperemia edema frequently seen after inhalation injury without any significant alterations in MAP or CI. .A Abdi S; Traber LD; Herndon DN; Redl G; Curry B; Traber DL. .I 274781 .U 91005278 .S Crit Care Med 9101; 18(10):1158-63 .M Adult; Aged; Blood Flow Velocity; Comparative Study; Echocardiography, Doppler/IS/*ST; Evaluation Studies; Female; Heart Catheterization/*ST; Heart Diseases/*DI/PP/US; Hemodynamics; Human; Male; Middle Age; Pulmonary Wedge Pressure/*; Reproducibility of Results. .T Noninvasive determination of pulmonary artery wedge pressure: comparative analysis of pulsed Doppler echocardiography and right heart catheterization. .P JOURNAL ARTICLE. .W To compare left ventricular filling variables as derived by transmitral pulsed Doppler echocardiography (tpDE) and hemodynamic variables as assessed at right heart catheterization (RHC), 104 ICU patients (64 male, 40 female) aged 26 to 73 yr (mean 54.6 +/- 10.3) without valvular heart disease were examined. Simultaneously with RHC, transmitral flow velocity profiles were obtained by tpDE, and the ratio of the velocity-time integrals of late diastolic active (A wave) and early diastolic passive inflow into the left ventricle (E wave) was calculated (A/E ratio). Invasively determined pulmonary capillary wedge pressure (WP) ranged from 3 to 36 mm Hg (median 13.35, 5%/95% 6/31 mm Hg). Linear regression analysis showed a highly significant correlation between the A/E ratio and WP (r = .98, p less than .001, standard error of the estimate [SEE] = 0.10). The A/E ratio also correlated with other hemodynamic variables such as cardiac output (r = -.68, p less than .001, SEE = 0.33), cardiac index (r = -.74, p less than .001, SEE = 0.31), and stroke volume index (r = -.68, p less than .001, SEE = 0.34). The interobserver agreement (derived by intraclass correlation analysis between two examiners) on the A/E ratio was high (r = .95, p less than .001, n = 26). We conclude that WP can be accurately determined noninvasively by tpDE. For the assessment of systolic ventricular function, tpDE is of limited diagnostic value. .A Stork TV; Muller RM; Piske GJ; Ewert CO; Wienhold S; Hochrein H. .I 274782 .U 91005280 .S Crit Care Med 9101; 18(10):1167-74 .M Animal; Cats; Disease Models, Animal; Dogs; Homeostasis; Human; Inflammation/PP; Kallikrein-Kinin System/PH; Kinins/BI/PH/*TU; Multiple Organ Failure/DT; Primates; Prostaglandins/BI/PH/*TU; Rabbits; Rats; Sheep; Stress/*DT/PP; Surgery, Operative/*AE. .T Kinin/prostaglandin system: its therapeutic value in surgical stress. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Multiple system organ failure as a consequence of injury or sepsis remains the major reason for death in critically ill patients. One of the treatment concepts that has recently attracted clinical attention is the administration of kinins and prostaglandins (PGs). On the basis of experimental data, there is reason to believe that these compounds may have the potential to manipulate favorably certain processes and mechanisms (such as inflammatory or ischemic reactions) thought to be important in the pathophysiology of surgical stress. However, thus far, information on those effects in humans is still scarce. On the other hand, administration of kinins and PGs is technically possible and can be performed safely, even in intensive care patients. Therefore, different techniques, effects, and side-effects of kinin/PG therapy deserve clinical testing. It remains to be seen whether this concept will be useful in the treatment of critically ill surgical patients. .A Hartl WH; Herndon DN; Wolfe RR. .I 274783 .U 91005281 .S Crit Care Med 9101; 18(10):1175-6 .M Antibiotics/TU; Case Report; Child; Child, Preschool; Female; Human; Male; Near Drowning/*CO; Pneumococcal Infections/DT/*ET; Pneumonia/DT/*ET; Risk Factors; Septicemia/DT/*ET. .T Streptococcus pneumoniae bacteremia associated with near-drowning. .P JOURNAL ARTICLE. .A Vernon DD; Banner W Jr; Cantwell GP; Holzman BH; Bolte RG; Dean JM. .I 274784 .U 91005282 .S Crit Care Med 9101; 18(10):1177-9 .M Adult; Case Report; Clinical Protocols; Critical Care/*; Electromyography; Female; Human; Injections, Intravenous; Male; Middle Age; Monitoring, Physiologic; Neural Conduction; Neurologic Examination; Paralysis/*CI/DI/PC; Vecuronium/AD/*AE/PK. .T Prolonged neuromuscular blockade after long-term infusion of vecuronium bromide in the intensive care unit. .P JOURNAL ARTICLE. .A Partridge BL; Abrams JH; Bazemore C; Rubin R. .I 274785 .U 91005283 .S Crit Care Med 9101; 18(10):1180-1 .M Adult; Angiography; Bromocriptine/AD/*AE/PD; Carotid Artery Thrombosis/*CI/DT/RA; Carotid Artery, Internal; Case Report; Heparin/TU; Human; Humerus/*BS; Male; Methylprednisolone/TU; Puerperium/*; Thiopental/TU; Thrombosis/*CI/DT/RA. .T Acute thrombotic accident in the postpartum period in a patient receiving bromocriptine. .P JOURNAL ARTICLE. .A Maurel C; Abhay K; Schaeffer A; Lange F; Castot A; Melon E. .I 274786 .U 91005285 .S Crit Care Med 9101; 18(10):1183-4 .M Human; Shock, Septic/DI/DT/*PP; Stroke Volume/*. .T Myocardial depression during septic shock in humans [editorial] .P EDITORIAL. .A Parrillo JE. .I 274787 .U 91005286 .S Crit Care Med 9101; 18(10):1185-6 .M Clinical Protocols/*ST; Human; Research Design/*ST; Shock, Septic/PP/*TH. .T Use of survivors' cardiorespiratory values as therapeutic goals in septic shock [letter; comment] .P COMMENT; LETTER. .A Heiselman DE; Ward G. .I 274788 .U 91005287 .S Crit Care Med 9101; 18(10):1186-7 .M Catheterization, Central Venous/*AE; Human; Immunologic Deficiency Syndromes/*CO; Infection/EP/*ET. .T Percutaneous central venous catheterization in a pediatric intensive care unit: a survival analysis of complications [letter; comment] .P COMMENT; LETTER. .A Moler FW; Custer JR. .I 274789 .U 91005288 .S Crit Care Med 9101; 18(10):1187 .M Adult; Case Report; Communication/*; Depressive Disorder/*ET; Female; Human; Intensive Care Units/*; Physician-Patient Relations/*. .T Acronym-associated illness [letter] .P LETTER. .A Koonings PP; Grimes DA; Schlaerth JB. .I 274790 .U 91005289 .S Crit Care Med 9101; 18(10):1187 .M Cardiac Output/*; Catheterization, Swan-Ganz/*AE; Catheters, Indwelling/EC/*SD; Human. .T Complications of pulmonary artery catheter insertion [letter; comment] .P COMMENT; LETTER. .A Gingles B. .I 274791 .U 91005290 .S Crit Care Med 9101; 18(10):1187 .M Catheterization, Swan-Ganz/AE/*MT; Human; Internship and Residency/*; Prospective Studies. .T Subclavian introduction technique of the pulmonary artery catheter [letter; comment] .P COMMENT; LETTER. .A Sanchez-Izquierdo Riera JA; Garcia Fuentes C; Montejo Gonzalez JC; Lopez EA. .I 274792 .U 91005291 .S Crit Care Med 9101; 18(10):1187-90 .M Pulmonary Circulation/*; Respiratory Distress Syndrome, Adult/BL/*PP; Severity of Illness Index/*. .T Who needs the respiratory index/pulmonary shunt relationship? [letter] .P LETTER. .A Zetterstrom H. .I 274793 .U 91005292 .S Crit Care Med 9101; 18(10):1190-1 .M Antibiotics/*TU; Intensive Care Units/*; Pneumonia/*DT/ET. .T Prevention of pneumonia in an intensive care unit [letter; comment] .P COMMENT; LETTER. .A Stoutenbeek CP. .I 274794 .U 91005293 .S Crit Care Med 9101; 18(10):1191-2 .M Comparative Study; Heart Valve Diseases/*SU; Human; Hypertension, Pulmonary/*DT; Ketanserin/*TU; Nitroprusside/*TU; Postoperative Complications/*DT. .T Ketanserin in the treatment of pulmonary hypertension after valvular surgery: comparison with sodium nitroprusside [letter; comment] .P COMMENT; LETTER. .A Dehring DJ. .I 274795 .U 91005294 .S Crit Care Med 9101; 18(10):1192-3 .M Gastrointestinal Hemorrhage/*PC; Intensive Care Units, Pediatric/*; Physician's Practice Patterns/*; Questionnaires. .T Attitude of pediatric intensivists toward prophylaxis of upper gastrointestinal bleeding [letter] .P LETTER. .A Lacroix J; Gauthier M. .I 274796 .U 91005295 .S Crit Care Med 9101; 18(10):1193-4 .M Cimetidine/*TU; Famotidine/*TU; Gastrointestinal Hemorrhage/*DT; Human; Research/*ST. .T Continuous infusion H2-receptor therapy [letter; comment] .P COMMENT; LETTER. .A Karlstadt RG; Palmer RH. .I 274797 .U 91005308 .S Curr Probl Surg 9101; 27(10):621-705 .M Adult; Cardiac Output, Low/*TH; Child; Extracorporeal Membrane Oxygenation/*/MT/TD; Human; Infant, Newborn; Respiratory Distress Syndrome/*TH; Respiratory Distress Syndrome, Adult/*TH; Support, U.S. Gov't, P.H.S.. .T Extracorporeal life support for cardiopulmonary failure. .P JOURNAL ARTICLE; REVIEW; REVIEW LITERATURE. .A Bartlett RH. .I 274798 .U 91005309 .S Curr Probl Surg 9101; 27(11):709-72 .M Cholelithiasis/*TH; Cholesterol; Human; Lithotripsy/*/IS/MT. .T Biliary lithotripsy. .P JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC. .A Prystowsky JB; Nahrwold DL; Rege RV. .I 274799 .U 91005336 .S Dysphagia 9101; 4(4):187-242 .M Deglutition Disorders/*DH; Human; Nutritional Requirements/*. .T Nutritional aspects of dysphagia. .P OVERALL. .I 274800 .U 91005337 .S Dysphagia 9101; 4(4):189-95 .M Adult; Diet; Female; Human; Male; Nutrition Assessment/*; Nutrition Disorders; Nutritional Requirements/*. .T Nutritional assessment and requirements. .P JOURNAL ARTICLE. .W Nutrition plays an important role in health and disease, both in prevention and treatment. Increasing emphasis is being placed upon nutrition as a therapeutic tool to decrease the morbidity and mortality associated with obesity, hypertension, coronary artery disease, and cancer. Adequate nutrition should be a concern for all health care workers because of its impact on the overall health of patients. Health care professionals should be familiar with the essentials of nutritional assessment and basic nutritional requirements and be able to improve their patients' care in the face of nutritional deficiencies or excesses. .A Kamel PL. .I 274801 .U 91005338 .S Dysphagia 9101; 4(4):196-201 .M Aged; Aged, 80 and over; Aging/*PH; Human; Nutrition/*PH; Nutritional Status. .T Nutrition and the older adult. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W The surge in interest in aging research has led to a growing awareness of the importance of adequate nutritional status in the elderly. This paper highlights the current state of our knowledge of nutrition in the older adult with regard to age-related alterations in nutritional status, the effects of altered nutritional status on the general well-being of the elderly, and the contributions of alcohol and drugs to altered nutritional status. Nutritional assessment techniques used for the elderly and directions for future research are discussed. .A Granieri E. .I 274802 .U 91005342 .S Dysphagia 9101; 4(4):220-6 .M Animal; Calcitonin Gene-Related Peptide/AN; Esophagus/CH/IR; Fluorescent Antibody Technique; Nerve Fibers/*CH; Neuropeptide Y/AN; Neuropeptides/*AN; Pharyngeal Muscles/CH/IR; Pharynx/CH/*IR; Rabbits; Substance P/AN; Support, Non-U.S. Gov't; Vasoactive Intestinal Peptide/AN. .T Neuropeptide-containing nerve fibers in the pharynx of the rabbit. .P JOURNAL ARTICLE. .W The distribution of peptide-containing nerve fibers in the pharyngeal region of rabbits was studied by immunocytochemistry. Neuropeptide Y (NPY)-containing fibers were numerous around blood vessels and moderate in number among bundles of striated muscle fibers. A few NPY-containing fibers were seen around seromucous glands and beneath the epithelium. Nerve fibers containing vasoactive intestinal peptide (VIP) were numerous around seromucous glands and moderate in number around blood vessels, bundles of muscle, and in the subepithelial layer. A few nerve fibers containing substance P (SP) were seen around blood vessels, seromucous glands, among bundles of muscle, and in the subepithelial layer. Nerve fibers containing calcitonin gene-related peptide (CGRP) were numerous. They were distributed close to blood vessels, among bundles of muscle, in the subepithelial layer, and within the epithelium. A conspicuous finding was the occurrence of CGRP within motor end plates of striated muscle. .A Uddman R; Ekberg O; Malmberg L; Borgstrom P; Fernstrom G; Ekstrom J; Sundler F. .I 274803 .U 91005343 .S Dysphagia 9101; 4(4):227-35 .M Adolescence; Adult; Aged; Aged, 80 and over; Cerebrovascular Disorders/PP; Child; Child, Preschool; Deglutition/*PH; Deglutition Disorders/*DI/PP; Female; Human; Infant; Male; Middle Age; Motor Neurons; Neuromuscular Diseases/PP; Oropharynx/PH; Pressure; Respiration/*PH; Respiratory Airflow/PH; Support, Non-U.S. Gov't. .T The Exeter Dysphagia Assessment Technique. .P JOURNAL ARTICLE. .W The Exeter Dysphagia Assessment Technique (EDAT) uses noninvasive equipment to record, simultaneously, "feeding respiratory patterns," the time drink entered the mouth, and associated swallow sounds during feeding. The easily portable equipment enabled patients' swallowing ability to be tested, at the bedside if necessary, using a small amount of fruit-flavored drink. The results appear in chart form. EDAT findings from groups of normal subjects aged 2-90 years were compared with those from patients with dysphagia of neurologic origin and normal subjects under experimental feeding conditions. The results revealed maturation of the feeding respiratory pattern in the teenage years and remarkable consistency thereafter. Differences in the recordings between the normal and abnormal subjects were sufficiently marked to allow the findings to be used in the diagnosis of other patients with dysphagia of doubtful neurologic cause. Interpretation of the charts and recorded timings of the oral and pharyngeal stages of swallowing permitted a more accurate identification of sensory nerve, motor nerve, and functional involvement causing dysphagia of neurologic origin and may be used as a guide to the origin of the sensory deficit. .A Selley WG; Flack FC; Ellis RE; Brooks WA. .I 274804 .U 91005344 .S Dysphagia 9101; 4(4):236-42 .M Adult; Aged; Deglutition/*PH; Esophagus/PH; Female; Fluoroscopy; Food; Human; Hyoid Bone/PH; Male; Middle Age; Mouth/PH; Oropharynx/PH; Reproducibility of Results; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Videotape Recording. .T Test-retest variability in normal swallowing. .P JOURNAL ARTICLE. .W The test-retest variability of the modified barium swallow study using videofluoroscopy was analyzed. Sixteen normal subjects (8 men, 8 women) were organized into 2 age groups: middle-aged group (mean, 45 years) and old-age group (mean, 66 years). Nine durational measures of the swallow were evaluated. There were no statistically significant differences for any of the measures between the initial test and a retest conducted days later. The findings suggest that, on the whole, normal subjects perform similarly on test and a retest. However, the variability displayed by these normal subjects may be clinically significant, indicating that test-retest swallowing duration measures require careful interpretation. .A Lof GL; Robbins J. .I 274805 .U 91005346 .S Dysphagia 9101; 5(2):110-3 .M Deglutition Disorders/*; Human. .T Third Symposium on Dysphagia. March 22-23, 1990. Abstracts. .P MEETING REPORT; OVERALL. .I 274806 .U 91005350 .S Dysphagia 9101; 5(2):61-71 .M Aged; Aged, 80 and over; Foreign Bodies/*/CO/DI/PP/TH; Human; Larynx/*; Pneumonia, Aspiration/*. .T Aspiration and the elderly. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Aspiration is prevalent in the elderly but its association with impairment of oral intake and gastroesophageal reflux is often misunderstood. This paper describes the causes, pathophysiology, and consequences of aspiration and their unique features in aged persons. It also explains how videofluoroscopic evaluation can assess current function while limiting factors that result in misinformation. The management of aspiration is discussed, emphasizing the importance and difficulties in maintaining functional well-being and possible complications of therapy. .A Feinberg MJ; Knebl J; Tully J; Segall L. .I 274807 .U 91005351 .S Dysphagia 9101; 5(2):72-6 .M Aged; Aging/*/PH; Diet; Human; Nutrition/*/PH; Weight Loss. .T Overview of geriatric nutrition. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Restoration and maintenance of optimal nutritional status in the long-term care setting may enhance the quality of life for geriatric patients. The elderly are at increased risk for poor nutrition due to age-related physiological and psychosocial changes, as well as the added toll of chronic disease. All of these may have a negative impact on adequate food intake. Health care providers must identify and address nutrition-related problems in a timely manner to correct nutrient imbalances and restore nutritional well-being in this population. .A Curran J. .I 274808 .U 91005355 .S Dysphagia 9101; 5(2):96-101 .M Aged; Dehydration/*PC; Eating; Florida; Food Services/*/MA; Human; Nursing Homes/*; Nutrition/*; Nutrition Disorders/*PC. .T Nature, nurture, nutrition: interdisciplinary programs to address the prevention of malnutrition and dehydration. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Malnutrition and dehydration are common problems in nursing home patients. One explanation for this may be the large number of patients requiring feeding assistance. The Dysphagia Team at the Department of Veterans Affairs Medical Center in Miami, Florida served as the primary source in the expansion of a nutritionally supportive environment to assist in the prevention of malnutrition and dehydration in patients with feeding/swallowing disorders. "Silver Spoons," a program in which volunteers provide supervised feeding, "Happy Hour," a time each day during which an atmosphere is provided that encourages socialization and hydration, and "Second Seating," during which lunch is provided for patients who require modification of eating style, food texture, or timing are described. Analysis of the program's outcomes show it to be timely, pleasing to patients, and cost-effective. .A Musson ND; Kincaid J; Ryan P; Glussman B; Varone L; Gamarra N; Wilson R; Reefe W; Silverman M. .I 274809 .U 91005356 .S Chest 9101; 98(4):1006 .M Ethics, Medical; Expert Testimony/*ST; Human. .T ACCP guidelines for an expert witness [see comments] .P JOURNAL ARTICLE. .A Bone RC; Rosenow EC. .I 274810 .U 91005357 .S Chest 9101; 98(4):1007-11 .M Air Pollutants, Occupational/AE; Asthma/DI/*ET; Human; Occupational Diseases/*/DI; Time Factors. .T Medical-legal definition of occupational asthma. .P JOURNAL ARTICLE. .A Smith DD. .I 274811 .U 91005358 .S Chest 9101; 98(4):1012-3 .M Adult; Anesthesia, Inhalation; Bronchodilator Agents/AD/AE; Case Report; Curare-Like Agents/AD; Enflurane/AD/*AE; Female; Halothane/AD/*AE; Human; Quadriplegia/*CI; Respiration, Artificial; Status Asthmaticus/*TH. .T Transient neuromuscular impairment resulting from prolonged inhalation of halothane and enflurane. .P JOURNAL ARTICLE. .W Inhalation anesthesia first with halothane followed by enflurane relieved a patient with status asthmaticus who was refractory to conventional therapy including mechanical ventilation. After 13 days of anesthesia while on mechanical ventilation and employing nondepolarizing muscle relaxants, significant neuromuscular impairment, manifested by tetraplegia and sensory disturbance, developed. Anesthesia was discontinued on day 14, and the patient was weaned from mechanical ventilation on day 16. Over the next two months, the neuromuscular impairment markedly improved. Halothane was associated with cardiac arrhythmias and hepatitis necessitating replacement by enflurane. Enflurane appeared to be as effective a treatment for refractory asthma as halothane. The most probable cause of the neuromuscular impairment in our patient was the long-term use of inhalation anesthetics or nondepolarizing muscle relaxants. .A Tanigaki T; Kondo T; Ohta Y; Yamabayashi H. .I 274812 .U 91005359 .S Chest 9101; 98(4):1014-5 .M Adult; Bronchopulmonary Sequestration/CO/*PA; Case Report; Female; Human; Infant, Newborn; Male; Pericardial Effusion/DI/ET/US; Pericardium/*PA; Pregnancy; Ultrasonography, Prenatal. .T Intrapericardial extralobar pulmonary sequestration in a neonate. .P JOURNAL ARTICLE. .W A huge pericardial effusion was diagnosed during fetal ultrasound examination performed in the 42nd week of pregnancy on a healthy 25-year-old woman. Immediately after the birth, a two-dimensional echocardiogram confirmed this finding in the infant, and an intrapericardial kidney-shaped solid mass measuring 45 x 56 x 15 mm, completely surrounded by pericardial effusion, was visualized to the left part of the heart. The heart was normal. No signs of cardiac tamponade were seen. At the age of two days, the mass was surgically resected and the pericardial fluid evacuated. Microscopic examination revealed that the mass was formed totally of normal lung tissue surrounded by normal pleura. To the best of our knowledge, this is the first case of intrapericardial extralobar sequestration consisting of an accessory lung with completely normal lung tissue. .A Levi A; Findler M; Dolfin T; Di Segni E; Vidne BA. .I 274813 .U 91005360 .S Chest 9101; 98(4):1016-7 .M Accidents, Traffic/*; Adult; Aorta, Thoracic/*IN/RA; Aortic Rupture/RA/*US; Case Report; Echocardiography, Doppler/*; Human; Male. .T Traumatic rupture of aorta. Diagnosis by Doppler echocardiography. .P JOURNAL ARTICLE. .W Traumatic rupture of aorta is a serious complication in accidents, mainly road accidents, with a high mortality unless an immediate diagnosis and surgical correction is made. A case of traumatic rupture of the aorta shown in the acute phase by Doppler-echocardiography is reported. This technique can be of great value in the study of patients with thoracic trauma who do not show clear signs of aortic rupture which require urgent aortography. .A Moya JL; de Pablo C; Sanchez M; Barrios V; Fraj J; Asin-Cardiel E. .I 274814 .U 91005361 .S Chest 9101; 98(4):1017-9 .M Aged; Case Report; Echocardiography; Female; Heart Murmurs/ET; Human; Hypertension, Portal/CO; Mitral Valve/*PP/US; Mitral Valve Insufficiency/*ET/PP/US; Mitral Valve Prolapse/*CO/PP/US; Systole/*. .T Transient mitral regurgitation due to mitral valve prolapse accompanied by systolic anterior motion of the mitral valve. .P JOURNAL ARTICLE. .W A grade 4/6 systolic murmur, systolic anterior motion of the mitral valve (SAM), and severe mitral regurgitation (MR) documented by two-dimensional Doppler echocardiography developed suddenly on the structurally normal heart of a patient with idiopathic portal hypertension. The patient did not have signs of congestive heart failure and the aforementioned phenomenon disappeared completely when the patient was in hepatic failure. This could be explained by a change in circulating blood volume either by gastrointestinal hemorrhage or hepatic failure. .A Iga K; Hori K; Takahashi S. .I 274815 .U 91005362 .S Chest 9101; 98(4):1019-20 .M Adult; Body Temperature; Case Report; Heart/*PP/RI; Human; Hypothermia/*PP/RI; Male; Myocardial Contraction; Radionuclide Ventriculography; Stroke Volume. .T The effect of prolonged hypothermia on cardiac function in a young patient with accidental hypothermia. .P JOURNAL ARTICLE. .W A 20-year-old man had accidental, prolonged, and severe hypothermia. Serial radionuclide ventriculography disclosed reduced myocardial contractility during hypothermia that resolved after warming. The effects of hypothermia on cardiac function are discussed. .A Maaravi Y; Weiss AT. .I 274816 .U 91005363 .S Chest 9101; 98(4):1021-3 .M Adult; Biopsy; Bronchoscopy; Case Report; Female; Glomangioma/*PA/UL; Human; Mitochondria/UL; Tracheal Neoplasms/*PA/UL. .T Oncocytic glomus tumor of the trachea. .P JOURNAL ARTICLE. .W An oncocytic variant of glomus tumor of the trachea occurred in a 47-year-old woman. She experienced intermittent cough and hemoptysis for about three years. Bronchoscopy and chest CT scan showed a small reddish polypoid tumor on the lower end of the trachea. Bronchoscopic biopsy was carefully done and was diagnosed as oncocytoma. A wedge resection of the tumor was done. Tumor cells were characterized by strongly eosinophilic granular cytoplasm on light microscopy and by numerous closely packed round or ovoid mitochondria with prominent tubular cristae on electron microscopy. They were arranged in a sheet around small vessels, as a result of which the biopsy diagnosis of oncocytoma was changed to oncocytic glomus tumor. To our knowledge, this is the first report of an oncocytic glomus tumor arising from the trachea. .A Shin DH; Park SS; Lee JH; Park MH; Lee JD. .I 274817 .U 91005364 .S Chest 9101; 98(4):1023-5 .M Adult; Asthma/PA/*RA; Bronchi/PA; Bronchiectasis/CO; Bronchography/*; Case Report; Female; Human; Lung/RA; Mucus/*. .T Mucoid impaction of upper lobe bronchi in the absence of proximal bronchiectasis. .P JOURNAL ARTICLE. .W Mucoid impaction is a complication of asthma and is frequently recurrent in patients with allergic bronchopulmonary aspergillosis (ABPA). This report describes a patient with asthma and recurrent bilateral well-circumscribed densities on chest roentgenogram in the absence of ABPA. Recognition of this clinical presentation may avoid the need for invasive diagnostic procedures or steroid therapy. .A Anderson WM. .I 274818 .U 91005365 .S Chest 9101; 98(4):1025-6 .M Aged; Diagnostic Errors; Female; Human; Lung/*RA; Lung Neoplasms/*RA; Male; Pulmonary Veins/*RA. .T Confluence of pulmonary veins simulating a pulmonary mass. .P JOURNAL ARTICLE. .W Confluence of the pulmonary veins commonly appears on the frontal view of the chest and generally is easily recognized as such. On plain film tomography, computerized tomography, and pulmonary angiography, the anatomy of convergence of pulmonary veins prior to common entry into the left atrium is clearly displayed. In this report, attention is called to the occasional appearance of confluence of the pulmonary veins on the lateral view of the chest as a clearly circumscribed round opacity mimicking a lung or mediastinal mass. .A Levin B. .I 274819 .U 91005366 .S Chest 9101; 98(4):1026-9 .M Adult; Aged; Case Report; Cyclosporins/AE/*TU; Female; Human; Lung Diseases/*DT/PA; Male; Sarcoidosis/*DT/PA; Skin Diseases/*DT/PA. .T Cyclosporine and chronic sarcoidosis. .P JOURNAL ARTICLE. .W Two patients with progressive sarcoidosis who had poor responses and side effects from corticosteroid therapy were treated with cyclosporine. Cyclosporine suppressed conventional markers of inflammation and there was clinical improvement in one patient, but the disease recurred when therapy was discontinued. The second patient who had diabetes mellitus developed unstable glucose metabolism when given cyclosporine. This unstable diabetes mellitus together with side effects of nausea and vomiting resulted in weight loss and inadequate serum therapeutic levels that was associated with a poor therapeutic response to the cyclosporine. The major side effects in both patients were headache and gastrointestinal symptoms, but there was no renal dysfunction. We conclude that while corticosteroids remain the mainstay of sarcoid therapy, when these drugs have not been successful for the skin manifestations of the disease, a trial of cyclosporine may be justified. .A York EL; Kovithavongs T; Man SF; Rebuck AS; Sproule BJ. .I 274820 .U 91005367 .S Chest 9101; 98(4):1029-32 .M Blood Volume/DE; Case Report; Fludrocortisone/*TU; Heart/PP; Hemodynamics/DE; Human; Hypotension, Orthostatic/*DT/ET/PP; Male; Middle Age; Myocardial Infarction/*CO/PP; Pulmonary Wedge Pressure. .T Orthostatic hypotension following right ventricular myocardial infarction corrected with mineralocorticoid therapy. .P JOURNAL ARTICLE. .W Severe hypotension while standing became a problem in a patient after discharge from the hospital following right ventricular myocardial infarction. Hemodynamic studies showed that right ventricular systolic function did not maintain adequate left ventricular preload and that the patient did not compensate for cardiac dysfunction by increasing blood volume. Volume expansion by mineralocorticoid therapy corrected the orthostatic hypotension and ameliorated symptoms. Hypotension eventually resolved and therapy was stopped four months after the myocardial infarction. .A Hill PE; Mason TJ; Provus R; Neill WA. .I 274821 .U 91005368 .S Chest 9101; 98(4):1032-4 .M Adult; Case Report; Chronic Disease; Colectomy/*; Colitis, Ulcerative/CO/SU; Female; Hepatic Encephalopathy/CO/SU; Human; Liver Transplantation/*; Positive-Pressure Respiration; Respiratory Distress Syndrome, Adult/CO/*PP/RA; Septicemia/CO. .T Resolution of the adult respiratory distress syndrome following colectomy and liver transplantation. .P JOURNAL ARTICLE. .W A 32-year-old woman with liver failure from end-stage cirrhosis and ulcerative colitis developed septicemia and severe ARDS. Subtotal colectomy and a successful liver transplantation resulted in complete resolution of the ARDS. .A Ali M; Wall WJ. .I 274822 .U 91005369 .S Chest 9101; 98(4):1034-7 .M Adult; Bone Marrow Transplantation/*AE; Bronchiolitis Obliterans/ET/PA/RA; Case Report; Cytomegalic Inclusion Disease/*ET/IM/TH; Human; Male; Pneumonia, Viral/*ET/IM/TH; Support, Non-U.S. Gov't. .T Cytomegalovirus pneumonia in allogeneic bone marrow transplantation. An immunopathologic process? .P JOURNAL ARTICLE. .W Recent literature suggests that CMV pneumonia is an immunopathologic process. This case report summarizes the clinical course of a patient which supports this hypothesis. The patient is the recipient of an allogeneic BMT who recovered from an episode of CMV pneumonia that occurred about two months after the transplant. Despite recovery from the viral infection, follow-up BALs revealed persistent lymphocytosis in an apparent asymptomatic patient. He subsequently developed BOOP about four months after the initial CMV infection. These observations suggest that the viral infection may have resulted in the activation of the host's cell-mediated response and provides evidence to support the hypothesis that CMV pneumonia is an immune-mediated process. .A Chien J; Chan CK; Chamberlain D; Patterson B; Fyles G; Minden M; Meharchand J; Messner H. .I 274823 .U 91005370 .S Chest 9101; 98(4):1037-9 .M Adult; Cardiac Output, Low/ET; Case Report; Diagnosis, Differential; Female; Human; Pulmonary Veno-Occlusive Disease/*/CO/PA/RA. .T Florid pulmonary veno-occlusive disease. .P JOURNAL ARTICLE. .W A young woman presented with rapidly progressive dyspnea and clinical findings strongly suggestive of primary pulmonary hypertension or possible pulmonary embolism (or both). She died of acute right-sided heart failure. A diagnosis of pulmonary veno-occlusive disease was made at autopsy. Approximately 100 cases of this disease have been reported previously in the literature. We describe a patient with a particularly florid progression of this unusual disease. Death occurred within six weeks of the onset of symptoms. .A Nawaz S; Dobersen MJ; Blount SG Jr; Firminger HI; Petty TL. .I 274824 .U 91005371 .S Chest 9101; 98(4):1040-1 .M Catheterization, Central Venous/*MT; Human; Jugular Veins/*/RA; Thoracic Radiography. .T Triple-lumen central venous access via the external jugular vein [letter] .P LETTER. .A Manishen WJ; Paradowski L. .I 274825 .U 91005372 .S Chest 9101; 98(4):1041 .M Case Report; Human; Male; Middle Age; Pneumocephalus/*ET/RA; Spinal Puncture/*AE. .T Pneumocephalus in association with lumbar punctures [letter; comment] .P COMMENT; LETTER. .A Flora GS; Tuchschmidt JA; Sharma OP. .I 274826 .U 91005373 .S Chest 9101; 98(4):1041-2 .M Adult; Case Report; Drug Interactions; Female; Gemfibrozil/*AE; Human; Warfarin/*AE. .T Gemfibrozil interaction with warfarin sodium (coumadin) [letter] .P LETTER. .A Ahmad S. .I 274827 .U 91005374 .S Chest 9101; 98(4):1042 .M Anemia, Sickle Cell/*CO; Human; Hypertension, Pulmonary/DI/*ET; Pulmonary Embolism/ET. .T Pulmonary hypertension and sickle hemoglobinopathy [letter; comment] .P COMMENT; LETTER. .A Verresen D; De Backer W; Vermeire P. .I 274828 .U 91005375 .S Chest 9101; 98(4):1042-3 .M Biopsy/*MT; Freezing; Human; Lung/*PA; Pleura/*PA. .T Pleural and lung cryobiopsies [letter] .P LETTER. .A Homasson JP; Lange F. .I 274829 .U 91005377 .S Chest 9101; 98(4):1043 .M Adult; Case Report; Charcot-Marie Disease/CO/*PP; Human; Male; Neural Conduction; Phrenic Nerve/*PP; Respiratory Paralysis/ET. .T Phrenic nerve involvement in Charcot-Marie-Tooth disease [letter; comment] .P COMMENT; LETTER. .A Snyder RW; Mishel HS; Christensen GC 3d. .I 274830 .U 91005378 .S Chest 9101; 98(4):1043-7 .M Combined Modality Therapy; Human; Lung Neoplasms/*TH; Lymphangiomyoma/*TH. .T Lymphangiomyomatosis [letter] .P LETTER. .I 274831 .U 91005379 .S Chest 9101; 98(4):1047-8 .M Human; Pulmonary Embolism/RA/*RI. .T Testing for pulmonary embolism [letter; comment] .P COMMENT; LETTER. .A Shaheen MZ; Windebank WJ. .I 274832 .U 91005380 .S Chest 9101; 98(4):1048 .M Adult; Amyloidosis/*CO/PA; Case Report; Human; Kidney Diseases/*CO/PA; Male; Pulmonary Alveolar Proteinosis/*CO/DI. .T Pulmonary alveolar phospholipoproteinosis associated with amyloidosis [letter] .P LETTER. .A Merino-Angulo A; Perez-Marti M; Diaz de Otazu R. .I 274833 .U 91005381 .S Chest 9101; 98(4):785-6 .M Educational Status; Emergencies; Hypertension/ET/*TH; Pulmonary Disease (Specialty)/*; Questionnaires; Societies, Medical/*. .T American College of Chest Physicians' Consensus Panel on Hypertensive Emergencies [editorial] .P EDITORIAL. .A Frohlich ED. .I 274834 .U 91005382 .S Chest 9101; 98(4):786 .M Ethics, Medical/*; Expert Testimony/*. .T ACCP statement on the expert witness [editorial; comment] .P COMMENT; EDITORIAL. .A Rosenow EC 3d. .I 274835 .U 91005383 .S Chest 9101; 98(4):786-7 .M Catheterization/IS; Fiber Optics; Human; Monitoring, Physiologic/IS; Oximetry/IS; Oxygen/*BL; Veins. .T Mixed venous saturation. The puzzle is still incomplete [editorial; comment] .P COMMENT; EDITORIAL. .A Gettinger A. .I 274836 .U 91005384 .S Chest 9101; 98(4):787-9 .M Epinephrine/AD/TU; Heart Arrest/DT/PP; Human; Resuscitation/*; Vasoconstrictor Agents/*TU. .T Vasoconstrictors during CPR. Are they used optimally? [editorial; comment] .P COMMENT; EDITORIAL. .A Halperin HR; Guerci AD. .I 274837 .U 91005385 .S Chest 9101; 98(4):789-90 .M Human; Internal Mammary-Coronary Artery Anastomosis; Mammary Arteries/*SU; Regional Blood Flow; Sternum/*BS. .T Effect of internal mammary arterial mobilization on sternal blood flow [editorial; comment] .P COMMENT; EDITORIAL. .A Meland NB. .I 274838 .U 91005386 .S Chest 9101; 98(4):790-1 .M Adrenal Cortex Hormones/*TU; Human; Lung Diseases, Obstructive/*DT; Recurrence. .T Recidivism revisited. A case for steroids in relapsing COPD? [editorial; comment] .P COMMENT; EDITORIAL. .A Powles AC. .I 274839 .U 91005387 .S Chest 9101; 98(4):791-2 .M Ambulatory Care/*; Human; Lung Diseases, Obstructive/*TH; Oxygen Inhalation Therapy/*. .T Ambulatory oxygen. The standard of care [editorial] .P EDITORIAL. .A Petty TL; O'Donohue WJ. .I 274840 .U 91005388 .S Chest 9101; 98(4):792-3 .M Communication; Human; Respiration, Artificial/*; Speech, Alaryngeal/*; Tracheostomy/*. .T Importance of verbal communication for the ventilator-dependent patient [editorial] .P EDITORIAL. .A Leder SB. .I 274841 .U 91005389 .S Chest 9101; 98(4):794-800 .M Adult; Aged; Chronic Disease; Female; Fibrosis/PA; Heart Enlargement/PA; Heart Ventricle/PA; Human; Lung Diseases, Obstructive/CO; Male; Middle Age; Myocardium/*PA; Organ Weight; Pulmonary Fibrosis/CO; Pulmonary Heart Disease/CO/*PA; Tuberculosis, Pulmonary/CO. .T Pathologic involvement of the left ventricle in chronic cor pulmonale. .P JOURNAL ARTICLE. .W To determine whether or not the left ventricle is pathologically involved in patients with chronic cor pulmonale, right and left ventricular weights, wall thickness, myocyte diameters, and percentage of fibrosis in 18 autopsied hearts were examined in patients with chronic pulmonary disease (CPD); ten had right ventricular hypertrophy on their electrocardiograms, and eight were without right ventricular hypertrophy. Five with extracardiopulmonary disease were used as controls. The weight of the right ventricle was significantly increased in CPD when compared to control subjects. Walls of both ventricles were significantly thicker in CPD. Myocyte diameters of both ventricles were significantly greater in CPD. The percentage of fibrosis in the right ventricle was significantly greater in CPD. The percentage of fibrosis in the left ventricle was significantly greater only in patients with right ventricular hypertrophy. We concluded that the left ventricle was also involved pathologically in patients with chronic cor pulmonale in the end stage of the disease. .A Kohama A; Tanouchi J; Hori M; Kitabatake A; Kamada T. .I 274842 .U 91005390 .S Chest 9101; 98(4):801-5 .M Acquired Immunodeficiency Syndrome/*CO; Bronchoalveolar Lavage Fluid/*PA; Human; Immune Tolerance/*; Lung/*UL; Pneumonia, Pneumocystis carinii/*CO/PA; Pulmonary Alveolar Proteinosis/*CO/PA; Support, Non-U.S. Gov't. .T Pulmonary alveolar proteinosis associated with Pneumocystis carinii. Ultrastructural identification in bronchoalveolar lavage in AIDS and immunocompromised non-AIDS patients. .P JOURNAL ARTICLE. .W Pneumocystis carinii (PC) has been recognized as frequently responsible for most opportunistic pulmonary infections occurring in immunocompromised AIDS and non-AIDS patients. Moreover, these patients can be considered at risk for secondary pulmonary alveolar proteinosis. Therefore, we have investigated the occurrence of associated secondary alveolar proteinosis and PC pneumonitis in AIDS and non-AIDS immunocompromised patients. In a series of 26 bronchoalveolar lavages (BAL) in patients with PC pneumonitis (19 AIDS and seven non-AIDS patients), we observed on light microscopy, in addition to the honeycombed material, areas of an extracellular material that had a different pattern which was suggestive of that described in alveolar proteinosis. A systematic ultrastructural study of these 26 BAL fluid samples demonstrated in each of them an accumulation of phospholipid surfactantlike extracellular material mixed or not with the PC cysts. In nine cases, the observation of lipoproteinaceous material on light microscopy and abundant phospholipid material with myelinlike and myelin tubular laminated structures on electron microscopy was highly suggestive of an associated pulmonary alveolar proteinosis (PAP). Such an accumulation of extracellular material was not observed in the 11 BAL fluid samples collected in immunocompromised patients (seven AIDS and four non-AIDS patients) without PC pneumonitis. These findings demonstrated a particular frequency of associated PAP with PC pneumonitis. These results raise important questions concerning (1) the consequence of such an alveolar accumulation of lipoproteinaceous material on the clinical status and prognosis of the pneumonitis, and (2) the mechanisms responsible for this accumulation. .A Tran Van Nhieu J; Vojtek AM; Bernaudin JF; Escudier E; Fleury-Feith J. .I 274843 .U 91005391 .S Chest 9101; 98(4):806-10 .M Aged; Angina Pectoris/*CO/PP; Chest Pain/*ET; Electrocardiography, Ambulatory; Esophageal Motility Disorders/*CO/PP; Esophagus/PP; Human; Hydrogen-Ion Concentration; Male; Manometry; Middle Age; Prospective Studies. .T Esophageal contribution to chest pain in patients with coronary artery disease. .P JOURNAL ARTICLE. .W We conducted a prospective study to determine the role of the esophagus in causing chest pain in patients with established CAD on optimum therapy. Thirty-two men with documented CAD who complained of frequent and usually daily retrosternal chest pain were evaluated. Following a standard esophageal manometry and acid perfusion test, simultaneous two-channel ambulatory Holter monitor and esophageal pH record tests were performed for 24 hours. Fifty-three episodes of chest pain were documented in 20 patients; 11 patients were free of pain. Of the 20 patients who complained of chest pains, 17 (85 percent) demonstrated at least one episode of PPR, defined as a drop in distal esophageal pH to less than 4 within ten minutes before or after the onset chest pain. Episodes of asymptomatic GER were common. The correlation of PPR with chest pain was 70 percent (37/53 episodes) and of ischemic ECG changes with chest pain 13 percent (7/53); in the remaining, there was no correlation with either. Two patients demonstrated simultaneous PPR and ischemic ECG changes. Seventeen esophageal motility abnormalities were observed in 14 patients (45 percent). It is our conclusion that esophageal disorders contribute to chest pain in patients with documented CAD. In this group, GER plays a greater role than in those with normal coronary arteries. In addition, esophageal motility disorders are common in these patients. Esophageal testing can be undertaken safely in these patients. .A Garcia-Pulido J; Patel PH; Hunter WC; Douglas JE; Thomas E. .I 274844 .U 91005392 .S Chest 9101; 98(4):811-5 .M Adult; Albuterol/AD/*AE; Bendroflumethiazide/AD/*AE; Drug Synergism; Drug Therapy, Combination; Electrocardiography/*DE; Human; Hypokalemia/*CI/PC; Spironolactone/AD/*PD; Triamterene/AD/*PD. .T Hypokalemic and ECG sequelae of combined beta-agonist/diuretic therapy. Protection by conventional doses of spironolactone but not triamterene. .P JOURNAL ARTICLE. .W Salbutamol (Albuterol) and diuretics are commonly prescribed together in patients with airflow obstruction and are associated with electrocardiographic effects. We have now investigated whether the use of potassium-sparing drugs might prevent the ECG sequelae of such combined therapy. Ten healthy subjects received seven days of randomized treatments with: placebo, bendrofluazide (5 mg), bendrofluazide plus triamterene 50 mg (conventional dose), or triamterene 200 mg (high dose), and bendrofluazide plus spironolactone (100 mg). Potassium and ECG responses to inhaled salbutamol, 2 mg, were measured after each treatment period. The T-wave flattening in response to bendrofluazide and salbutamol (0.24[CI, 0.19 to 0.29]mV) was attenuated by the addition of triamterene, 200 mg (0.33[CI, 0.28 to 0.37]mV; p less than 0.05) and spironolactone 100 mg (0.42[CI, 0.37 to 0.47]mV; p less than 0.01), but not by triamterene 50 mg (0.25[CI, 0.20 to 0.30]mV). Spironolactone and high dose triamterene also diminished the frequency of U waves and ST depression. The ECG effects mirrored hypokalemic responses which were also blunted by high dose (p less than 0.01) but not low dose triamterene, as well as by spironolactone (p less than 0.001). Thus, the use of high dose triamterene and spironolactone protected against the hypokalemic and ECG sequelae of combined beta-agonist/diuretic therapy, whereas a conventional dose of triamterene had no effect. These findings may be important in the prevention of a potentially dangerous interaction in susceptible patients taking this combination of drugs. .A Lipworth BJ; McDevitt DG; Struthers AD. .I 274845 .U 91005393 .S Chest 9101; 98(4):816-20 .M Adult; Aged; Female; Heart Failure, Congestive/PP/SU; Heart Transplantation/*; Hemodynamics; Human; Male; Middle Age; Pulmonary Diffusing Capacity; Respiratory Airflow; Respiratory Mechanics/*; Smoking/AE; Total Lung Capacity. .T Ventilatory and diffusion abnormalities in potential heart transplant recipients. .P JOURNAL ARTICLE. .W Few data are available concerning pulmonary function in patients with severe chronic congestive heart failure. Of 315 patients evaluated for potential cardiac transplantation at UCLA, 132 underwent pulmonary function tests. The latter patients had severe heart failure with a mean left ventricular ejection fraction of 19 percent and mean cardiac index of 2.1 L/min/m2. Diffusion impairment either alone or combined with restrictive and/or obstructive ventilatory defects occurred in 67 percent of the patients evaluated. Diffusion impairment occurred as the sole abnormality in 31 percent of the patients and in combination with a restrictive ventilatory defect in 21 percent. A reduction in diffusing capacity has not been previously described as a frequent finding in patients with chronic congestive heart failure. In contrast to other studies involving patients with acute heart failure, obstructive ventilatory defects were uncommon. None of the lung function abnormalities was associated with smoking status, prior drug use, chest roentgenographic changes, hemodynamic findings, or clinical features, including duration of congestive heart failure. The mechanism for the diffusion impairment is unclear but could be due to chronic passive congestion with pulmonary fibrosis and/or recurrent pulmonary emboli. Recognition of diffusion impairment as a common finding in patients with severe chronic congestive heart failure who are candidates for heart transplantation is important for proper interpretation of possible post-transplant changes in diffusing capacity due to other causes. .A Wright RS; Levine MS; Bellamy PE; Simmons MS; Batra P; Stevenson LW; Walden JA; Laks H; Tashkin DP. .I 274846 .U 91005394 .S Chest 9101; 98(4):821-8 .M Adult; Aged; Ambulatory Care Facilities; Asthma/CO/DI/DT/*PP; Female; Forced Expiratory Volume; Health Services/UT; Human; Male; Middle Age; Support, U.S. Gov't, P.H.S.; Vital Capacity. .T Characteristics and correlates of asthma in a university clinic population. .P JOURNAL ARTICLE. .W To contribute more comprehensive information about the characteristics of asthma, this article analyzed patients served by the University of Alabama at Birmingham Comprehensive Asthma Program. Their physicians rated one fifth of these patients as having "severe" asthma with the remainder about equally divided between "moderate" and "mild". One in two first received a diagnosis of asthma ten or more years previously. Common comorbidities were hypertension, obesity, rhinitis, bronchitis, sinusitis, and arthritis. One half had visited an emergency room or been hospitalized for asthma in the past year. Inhaled bronchodilators and continuous theophylline were the most commonly prescribed medications. Side effects, especially tachycardia and insomnia, were common and almost exclusively associated with theophylline or corticosteroid therapy. Spirometric assessment showed chronic airflow obstruction in those with more severe asthma. Prevalence of respiratory symptoms, intensity of medication regimen, incidence of side effects, and health care utilization increased as asthma severity increased. .A Bailey WC; Richards JM Jr; Manzella BA; Brooks CM; Windsor RA; Soong SJ. .I 274847 .U 91005395 .S Chest 9101; 98(4):829-34 .M Calcium Channel Blockers/*TU; Comparative Study; Diltiazem/TU; Exercise Test; Hemodynamics/*DE; Human; Hypertension, Pulmonary/*DT/ET/PP; Lung Diseases, Obstructive/*CO; Middle Age; Nifedipine/TU; Prospective Studies; Pulmonary Gas Exchange/DE; Verapamil/TU. .T Differential therapy with calcium antagonists in pulmonary hypertension secondary to COPD. Hemodynamic effects of nifedipine, diltiazem, and verapamil. .P JOURNAL ARTICLE. .W In 53 patients with COPD and precapillary pulmonary hypertension, we investigated the effect of three typical calcium antagonists on hemodynamics at rest and during bicycle ergometer exercise. In the responders, the decrease in pulmonary vascular resistance following nifedipine was 23 percent at rest (p less than 0.0005) and 35 percent during exercise (p less than 0.0005); following diltiazem, it was 10 percent at rest (p less than 0.05) and 23 percent during exercise (p less than 0.025); following verapamil, it was 22 percent at rest (p less than 0.005) and 11 percent during exercise (p less than 0.025). The cardiac index rose significantly at rest and under exercise only after the administration of nifedipine (+16 percent and +8 percent, resp). Nifedipine caused the most distinctive peripheral vasodilation. The heart rate increased slightly following nifedipine and decreased slightly following diltiazem and verapamil. After long-term therapy with nifedipine (13 +/- 5 months), the decrease in pulmonary artery pressure and pulmonary vascular resistance was no longer significant. In our opinion, the different hemodynamic action profiles will have consequences for the differential therapy in patients with COPD and pulmonary hypertension. .A Gassner A; Sommer G; Fridrich L; Magometschnigg D; Priol A. .I 274848 .U 91005397 .S Chest 9101; 98(4):840-4 .M Adolescence; Adult; Aged; Aged, 80 and over; Bacteria/*IP; Biopsy, Needle/*/AE/MT; Child; False Positive Reactions; Female; Fluorescent Antibody Technique; Human; Lung/*MI/PA; Male; Middle Age; Pneumonia/*DI/MI; Sensitivity and Specificity. .T Diagnostic value of nonfluoroscopic percutaneous lung needle aspiration in patients with pneumonia. .P JOURNAL ARTICLE. .W In forty-one patients (mean [+/- SD] age 51 +/- 19 years; range, 11 to 88 years; seven female and 34 male) with clinical signs and symptoms of pneumonia, we performed a nonfluoroscopic percutaneous lung needle (22 gauges) aspiration (PLNA) to investigate the diagnostic yield of this technique. All the patients were receiving antibiotics at the time of the study, and PLNA was performed either because of a lack of response to empiric antibiotic treatment or because of the severity of the pneumonia or the underlying condition of the patient. Eight patients were mechanically ventilated (MV) due to acute respiratory failure. The PLNA was performed at bedside and without fluoroscopic guidance. Twenty-two microorganisms were identified by means of stains and/or cultures of PLNA samples. Sensitivity of PLNA was 43 percent (18/41). We detected three false-positive cultures probably due to contamination from the skin area punctured. In the eight MV patients studied, the sensitivity of PLNA was 37.5 percent, and the microbiologic findings turned out to be crucial for the outcome of the patients. Pneumothorax developed in three patients (7 percent) after PLNA. None of these three patients developed a pleural infection but two of them required thoracostomy drainage. None of the MV patients presented complications. Our results showed that nonfluoroscopic PLNA is a technique with moderately good sensitivity and with a low rate of false-positive cultures (8 percent) to diagnose pulmonary infections in patients with unresponsiveness to empiric antibiotic treatment or with severe pneumonia. Further evaluation of its diagnostic value and complications in MV patients is needed, although our preliminary results suggest that PLNA can be an alternative technique to other methods for diagnosing pulmonary infections in patients receiving artificial ventilatory support. .A Torres A; Jimenez P; Puig de la Bellacasa J; Celis R; Gonzalez J; Gea J. .I 274849 .U 91005398 .S Chest 9101; 98(4):845-9 .M Acute Disease; Administration, Oral; Adrenal Cortex Hormones/*AD/TU; Aged; Bronchodilator Agents/TU; Emergency Service, Hospital; Forced Expiratory Volume/DE; Human; Hydrocortisone/AD/TU; Injections, Intravenous; Lung Diseases, Obstructive/*DT/PP; Methylprednisolone/AD/TU; Prednisone/AD/TU; Recurrence; Retrospective Studies; Vital Capacity/DE. .T Intravenous and oral corticosteroids for the prevention of relapse after treatment of decompensated COPD. Effect on patients with a history of multiple relapses [see comments] .P JOURNAL ARTICLE. .W To determine if a regimen of intravenous and oral corticosteroids reduces the relapse rate after treatment of decompensated COPD in the ED, 30 patients were studied. Forty-five visits in which intravenous and oral corticosteroids were given (T visits) were compared with an equal number of matched visits in which they were withheld (N visits). No differences were noted between T and N visits with respect to clinical findings, laboratory results and other forms of therapy. Treatment with corticosteroids reduced the relapse rate within 24 h of discharge. At 48 h, the cumulative relapse rate for T visits (8.9 percent) was significantly lower than for N visits (33.3 percent; p = 0.005). For patients with a history of multiple relapses, a regimen consisting of intravenous and oral corticosteroids reduces the risk of relapse after ED treatment of decompensated COPD. .A Murata GH; Gorby MS; Chick TW; Halperin AK. .I 274850 .U 91005401 .S Chest 9101; 98(4):866-70 .M Adrenergic Beta Receptor Agonists/*TU; Adult; Albuterol/TU; Asthma/*DT/PP; Bronchodilator Agents/*TU; Circadian Rhythm; Comparative Study; Double-Blind Method; Ethanolamines/*TU; Female; Forced Expiratory Volume/DE; Human; Male; Middle Age. .T Formoterol in the treatment of nocturnal asthma. .P JOURNAL ARTICLE. .W Formoterol fumarate is a new beta 2-adrenergic agonist with a long lasting effect. The bronchospasmolytic effect of 12 micrograms of formoterol was compared with that of 200 micrograms of albuterol (salbutamol) in a single-center, double-blind, randomized within-patient study. The drugs were given as aerosols by MDI to 16 patients with nocturnal asthma in a stable phase. The inhalations were given at 10 PM and the FEV1 values as parameter were measured before and at 1, 2, 6, 8, 10, and 12 hours afterwards. The FEV1 6 hours after administration of formoterol was significantly higher than that after albuterol (ANCOVA: p = 0.008), and this was still the case 12 hours after the test dose at 10 AM the following morning (ANCOVA: p = 0.009). At 4 AM, the FEV1 fell below the basic starting value after albuterol, whereas it remained at least 10 percent above the formoterol inhalation. Five patients required rescue therapy after albuterol and two after formoterol. We conclude that formoterol in a dose of 12 micrograms via MDI confers good protection against nocturnal asthma; this was only insufficient for some patients with severe asthma, and further studies with higher dosages in these patients are clearly indicated. .A Maesen FP; Smeets JJ; Gubbelmans HL; Zweers PG. .I 274851 .U 91005402 .S Chest 9101; 98(4):871-4 .M Adult; Forced Expiratory Volume; Glass/*; Human; Male; Middle Age; Occupations/*; Respiratory Airflow/*; Respiratory Muscles/PH; Vital Capacity/*. .T Pulmonary function in commercial glass blowers. .P JOURNAL ARTICLE. .W This study examined the pulmonary function of 87 male commercial glass factory workers. Statistical analysis of the data indicated that workers with full-time glass blowing job descriptions had significantly higher percent predicted values for FVC, FEV1 and significantly higher maximal inspiratory and expiratory muscle pressures than their cohorts with minimal or nonglass blowing job descriptions. The results of this study indicate that persons using their respiratory muscles as full-time blowers to manufacture commercial blown glass products have significantly greater lung function values than part-time blowers or their nonglass blowing co-workers. .A Munn NJ; Thomas SW; DeMesquita S. .I 274852 .U 91005403 .S Chest 9101; 98(4):875-7 .M Aged; Aorta/PA; Aortic Valve Insufficiency/*ET/PA/RA; Aortography; Case Report; Female; Human; Male; Temporal Arteritis/*CO. .T Severe aortic regurgitation as a late complication of temporal arteritis. .P JOURNAL ARTICLE. .W Two patients with a remote history of pathologically documented giant cell arteritis developed severe regurgitation. The first patient developed severe aortic regurgitation five years after the pathologic documentation of giant cell arteritis of the temporal arteries. Giant cell arteritis involvement of the aortic root was confirmed. The second patient developed aortic regurgitation seven years after pathologic documentation of giant cell arteries of the temporal arteries. Although pathologic confirmation of the aortic root process was not obtained, this case strengthens the clinical association between giant cell arteritis of the temporal arteries and subsequent aortic root dilatation and severe aortic regurgitation. Observation for signs of de novo severe aortic regurgitation is indicated in follow-up of patients with temporal arteritis. .A Costello JM Jr; Nicholson WJ. .I 274853 .U 91005406 .S Chest 9101; 98(4):886-9 .M Data Collection; Human; Lung/PH; Nomenclature/*; Respiratory Sounds/*. .T Lung sound nomenclature survey. .P JOURNAL ARTICLE. .W We report the terms used by 223 pulmonary physicians and 54 physicians in other specialties to describe eight recorded examples of lung sounds. The participants listened to the lung sounds at the 1988 American College of Chest Physicians annual convention and wrote "free form" answers. Pulmonary physicians used the terms "crackles" and "rales" with equal frequency to describe discontinuous adventitious lung sounds (ALS) and not at all to describe continuous ALS. Other physicians preferred the term "rales" in describing discontinuous ALS. The terms "wheeze" and "stridor" were used only in describing continuous ALS; however, the term "rhonchi" was frequently used to describe continuous and discontinuous ALS. The majority of participants recognized the normal breath sounds but not the pleural friction rub. Most did not use a qualifying adjective to describe ALS, and there was little agreement among those who did. The lung sound terminology used by physicians is not well standardized and the recommendations of the ATS/ACCP nomenclature subcommittee are not widely accepted. .A Wilkins RL; Dexter JR; Murphy RL Jr; DelBono EA. .I 274854 .U 91005407 .S Chest 9101; 98(4):890-3 .M Adult; Aged; Aged, 80 and over; Drainage/*/MT; Female; Human; Male; Middle Age; Patient Compliance; Peritoneal Cavity; Pleural Effusion/*SU; Postoperative Complications/*; Reoperation; Risk Factors; Veins. .T Predicting failure following shunting of pleural effusions. .P JOURNAL ARTICLE. .W We placed 43 shunts in 34 patients in five years. Twenty-four had malignant effusions and ten had benign effusions. Thirty-one patients had unilateral shunts, three had bilateral shunts and six required revisions for shunt failure. Two patients died after shunt placement from disease progression. Of the nine patients who experienced poor results, one was noncompliant in operating the shunt and eight had occluded shunts. In the 30 patients, who were compliant and had adequate length of follow-up, five had excellent results, 12 had good results, and five had fair results. Two of the patients with occluded shunts had good results after shunt revision; 24 patients had some symptomatic relief with shunting. Evaluation of factors including a history of prior abdominal surgery, performance status, and pleural fluid cell counts, differential, chemistries, and cytology revealed no significant differences between the patients who experienced shunt failure and those who had patent shunts. Shunting of pleural effusions is well tolerated and has good success rates in properly selected patients. .A Tzeng E; Ferguson MK. .I 274855 .U 91005408 .S Chest 9101; 98(4):894-9 .M Activities of Daily Living; Aged; Aged, 80 and over; Asthma/PP/PX; Attitude to Health; Family Practice; Female; Forced Expiratory Volume; Human; Lung Diseases, Obstructive/PP/*PX; Male; Middle Age; Quality of Life/*; Support, Non-U.S. Gov't; Vital Capacity. .T Quality of life in elderly patients with chronic nonspecific lung disease seen in family practice. .P JOURNAL ARTICLE. .W We studied the quality of life of elderly patients with chronic nonspecific lung disease (CNSLD) in family practice. We also investigated the relationship between patients' somatic condition and their quality of life. Seventy patients, aged 40 years or older, with a diagnosis or symptoms of CNSLD completed the Sickness Impact Profile (SIP) and the list of daily activities (DAL). Pulmonary function (FEV1, IVC) and respiratory symptoms were assessed. The results indicated that patients were more impaired in their physical and psychosocial functioning than healthy control subjects. Most lung function parameters showed no correlation with the SIP scores. The respiratory symptoms of wheezing and dyspnea were related to patients' quality of life. Patients with chronic obstructive pulmonary disease (COPD) were more restricted in their daily functioning than patients with asthma. Since the relationship between patients' somatic condition and their quality of life is weak, we recommend comprehensive care that encompasses psychosocial as well as somatic interventions. .A Schrier AC; Dekker FW; Kaptein AA; Dijkman JH. .I 274856 .U 91005409 .S Chest 9101; 98(4):900-6 .M Adult; Female; Forced Expiratory Volume; Human; Male; Middle Age; Mouth/*PH; Pressure; Respiration/*PH; Respiratory Function Tests; Rest; Vital Capacity. .T The relationship of resting ventilation to mouth occlusion pressure. An index of resting respiratory function. .P JOURNAL ARTICLE. .W In order to examine the relationship of mouth occlusion pressure (MOP), an index of central inspiratory neuromuscular drive, to age and sex and to resting ventilation (VE), measurements were made in the seated posture in 84 healthy, normal subjects (38 men, 46 women; ages 18-72 years, mean +/- SD = 39.8 +/- 14.5 years) and in 79 patients with either airways obstruction (n = 63) or restrictive lung disease (n = 16). In the normal subjects, there was no significant relationship between age or sex and MOP (expressed as P0.1), which is the mouth pressure developed against a complete occlusion at 0.1 s after the beginning of inspiration, and dP/dtmax, the maximal rate of rise of this pressure; mean +/- SD for P0.1 = 0.75 +/- 0.32 cmH2O, and dP/dtmax = 19.41 +/- 10.10 cmH2O/s. Similarly, there was no significant relationship between age or sex and VE/P0.1 or VE/dP/dtmax. In 99 percent of normal subjects (83 of 84), VE/P0.1 was greater than 8.0 L/min/cmH2O, whereas in only 1 of the 79 patients was the value greater than 7.9 L/min/cmH2O. While the mean values of P0.1 and dP/dtmax were significantly different between normal subjects and patients, there was considerable overlap, whereas the ratio VE/P0.1 or VE/dP/dtmax provided excellent differentiation between normal subjects and patients with lung disease. This index, which is easily measured and requires minimal patient cooperation, provides valuable information in the clinical assessment of ventilatory drive and lung mechanics. .A Scott GC; Burki NK. .I 274857 .U 91005410 .S Chest 9101; 98(4):907-10 .M Adult; Aerosols; Bronchial Spasm/CI; Cough/CI; Double-Blind Method; Female; Human; Lung/*DE; Male; Pentamidine/AD/*AE; Pneumonia, Pneumocystis carinii/PC; Respiratory Mechanics/DE; Support, Non-U.S. Gov't. .T Acute pulmonary effects of aerosolized pentamidine. A randomized controlled study. Toronto Aerosolized Pentamidine Study (TAPS) Group. .P JOURNAL ARTICLE. .W From June 1988 to February 1989, we enrolled 36 patients with human immunodeficiency virus into a randomized double-blind placebo-controlled trial assessing the efficacy and toxicity of aerosolized pentamidine (AP) as secondary prophylaxis for Pneumocystis carinii pneumonia. Each patient underwent spirometric evaluations before and after aerosolized treatment. There was no significant difference in the results of baseline pulmonary function tests between the two groups. Eleven patients (65 percent) in the AP group developed cough but only four demonstrated significant reduction in the forced expiratory flow rates after AP; four patients (21 percent) in the placebo group developed cough, but no significant change in the expiratory flow rates was noted. All bronchospastic episodes were self-limited and symptomatically responded to remedial inhaled albuterol (salbutamol) treatment. We conclude that AP treatment is frequently associated with coughing attacks (65 percent), but the actual incidence of bronchospasm on spirometry is much lower (24 percent) and is generally quite mild. .I 274858 .U 91005412 .S Chest 9101; 98(4):917-23 .M Adult; Aged; Bacteria/IP; Bronchi/PA; Bronchiolitis/MI/*PA/PP; Bronchoalveolar Lavage Fluid/*PA; Cell Count; Female; Human; Lung/PA; Macrophages/PA; Male; Middle Age; Neutrophils/*PA; Respiratory Mechanics. .T Neutrophilia in bronchoalveolar lavage fluid of diffuse panbronchiolitis. .P JOURNAL ARTICLE. .W The clinical and pathologic features of diffuse panbronchiolitis (DPB) have been well reported to date, although its pathogenesis remains unknown. In the present study, we performed bronchoalveolar lavage (BAL) on three patients with biopsy specimen-proven DPB and eight patients with highly probable DPB (six women and five men; one smoker and ten nonsmokers), nine patients with chronic bronchitis (all men, five smokers and four nonsmokers), and nine normal control subjects (six women and three men, all nonsmokers) to clarify the cell populations in the lower respiratory tract. Neutrophils comprised 55.3 +/- 24.4 percent of recovered cells by BAL in DPB patients but only 6.6 +/- 6.4 percent in chronic bronchitis patients, and 1.8 +/- 1.5 percent in normal control subjects (p less than 0.001, all comparisons). The DPB patients also exhibited a decreased percentage of alveolar macrophages (34.9 +/- 23.5 percent) compared with chronic bronchitis patients and normal control subjects (p less than 0.001, all comparisons). The percentage of lymphocytes of the recovered lavage cells in DPB patients did not differ from that in chronic bronchitis patients and normal control subjects. These results indicate that neutrophils play an important role in the pathogenesis of DPB. They also suggest that neutrophilia of BAL-recovered fluid is a common finding in diseases associated with bronchiolar inflammation despite some clinical and pathophysiologic differences. .A Ichikawa Y; Koga H; Tanaka M; Nakamura M; Tokunaga N; Kaji M. .I 274859 .U 91005413 .S Chest 9101; 98(4):924-7 .M Administration, Oral; Adult; Cytotoxicity, Immunologic/DE; Dose-Response Relationship, Drug; Dose-Response Relationship, Immunologic; Human; Killer Cells, Natural/DE/*IM; Theophylline/AD/*PD. .T Inhibition of natural killer cell activity by oral administration of theophylline. .P JOURNAL ARTICLE. .W Asthmatic patients have a low incidence of malignancies, and this is possibly due to higher NK cell activity in this population. Because theophylline is used widely in this population, we evaluated the influence of theophylline on NK cell activity in vitro and in vivo. The NK cell activity was significantly inhibited by direct addition of concentrations of aminophylline that exceeded 5 x 10(-5) M. To test whether such an effect can be observed in vivo, we administered one sustained-release tablet of theophylline (400 to 500 mg twice daily) to five normal volunteers for seven days. Significant inhibition of NK activity was noted after administration (mean percentage of inhibition, 41.3 percent), but the serum concentrations observed gave a mean value of 2 x 10(-5) M, which was lower than that yielding the same degree of inhibition by direct addition in vitro (about 20 x 10(-5) M). These results suggest that long-term theophylline therapy may inhibit NK cell activity, and thus more information would be needed to determine the position of such therapy in the management of asthmatic patients. .A Yokoyama A; Yamashita N; Mizushima Y; Yano S. .I 274860 .U 91005414 .S Chest 9101; 98(4):928-9 .M Accidents, Traffic/*; Adult; Asthma/*CI/PP; Bronchial Provocation Tests; Case Report; Chlorides/*AE; Forced Expiratory Volume; Human; Male; Middle Age; Silanes/*AE; Silicon/*AE; Sodium Hydroxide/*AE; Vital Capacity. .T Reactive airway dysfunction syndrome in three police officers following a roadside chemical spill. .P JOURNAL ARTICLE. .W The reactive airway dysfunction syndrome (RADS) is a recently described syndrome in which bronchial hyperreactivity and asthmatic symptoms develop in previously healthy individuals after a single large exposure to an irritating gas, fume, or vapor. We report a cluster of three Philadelphia police officers who developed RADS after a common exposure to toxic fumes from a roadside truck accident. Results of initial pulmonary function testing were normal in all three, and methacholine challenge was required for diagnosis in two out of the three. This syndrome needs to be recognized by physicians dealing with environmental or industrial medicine as a potential cause of loss of work or inability to perform on the job. Also, there is a potential for multiple individuals to develop this syndrome from a single incident. .A Promisloff RA; Lenchner GS; Phan A; Cichelli AV. .I 274861 .U 91005415 .S Chest 9101; 98(4):930-5 .M Glutathione/ME; Human; Lipid Peroxidation/*; Lung/*ME; Lung Diseases/ME/PP; Lung Neoplasms/*ME/PP; Male; Malondialdehyde/ME; Middle Age; Respiratory Mechanics; Smoking/*AE; Support, Non-U.S. Gov't; Time Factors. .T Pulmonary lipid peroxidation in cigarette smokers and lung cancer patients. .P JOURNAL ARTICLE. .W Lipid peroxidation (LPO) was studied in lung tissues of patients with lung cancer (LC, n = 37) or nonlung cancer (NLC, n = 13) and its relationships with the smoking habits and the degree of airway obstruction were investigated. Specimens of peripheral lung parenchyma, free of tumor tissue, were taken and the malondialdehyde (MDA) content was measured in the S-12 fractions. Airway obstruction was assessed by flow-volume curves, and data were expressed as percentage of the predicted values. Cigarettes smoked were expressed as pack-years. The patients with LC and NLC did not differ by MDA content, age, and number of pack-years. On the contrary, FEF75-85 and MEF75 were significantly lower in LC than in NLC patients (p less than 0.05). The MDA content was inversely correlated to number of days patients had refrained from smoking (r = -0.66, p less than 0.001). The MDA content was higher in recent smokers (ie, people smoking during the last 30 days before surgery) than in the other patients (0.136 +/- 0.007 vs 0.116 +/- 0.007 mumol/g of tissue, p less than 0.05) and, by considering only recent smokers, MDA content was higher in LC patients (0.144 +/- 0.008 mumol/g of tissue) than in NLC patients (0.113 +/- 0.014 mmol/g tissue, p = 0.059). When patients were divided into "high MDA" and "low MDA" groups, MEF75 was much lower in the high MDA group (35.1 +/- 3.4 percent) than in the low MDA group (55.1 +/- 8.1 percent) (p less than 0.01). These results suggest the following: (1) enhanced level of prooxidant state in the lungs is associated with recent cigarette smoking; (2) LC patients may be more prone than respective NLC patients to oxidative stress; (3) MDA level and degree of small airway obstruction were associated and differed between LC and NLC patients even though these groups did not differ in the percentage of recent smokers; and (4) a common free-radical mediated pathway may be active for both LC and small airway obstruction. .A Petruzzelli S; Hietanen E; Bartsch H; Camus AM; Mussi A; Angeletti CA; Saracci R; Giuntini C. .I 274862 .U 91005416 .S Chest 9101; 98(4):936-41 .M Adult; Asthma/BL/*PP; Bronchial Provocation Tests; Bronchoconstriction/*DE; Female; Forced Expiratory Flow Rates/DE; Forced Expiratory Volume/DE; Human; Isoproterenol/*PD; Leukocyte Count/DE; Male; Methacholine Chloride/DU; Platelet Activating Factor/*PD. .T Effect of PAF-acether inhalation on nonspecific bronchial reactivity and adrenergic response in normal and asthmatic subjects. .P JOURNAL ARTICLE. .W Bronchial hyperreactivity, although recognized as a hallmark of asthma, is not totally understood. Mast cell-derived mediators, including histamine, have been shown to cause immediate bronchoconstriction, but until recently, no single mediator has been shown to induce prolonged changes in airway reactivity. Recent reports indicate PAF-acether (PAF) can induce increased nonspecific bronchial reactivity in normal subjects but not in asthmatics. We sought to elucidate the role of PAF in airway hyperreactivity by comparing the effect of inhaled PAF on methacholine and isoproterenol airway responsiveness in six nonasthmatic and six asthmatic subjects. Neither nonspecific airway reactivity nor isoproterenol responsiveness was changed following PAF inhalation in the nonasthmatic subjects in the six days following PAF. Asthmatics had increased airway responsiveness to methacholine at two hours post-PAF, which did not persist. Responsiveness to isoproterenol did not change in the asthmatic subjects. Additional evaluation of the role of PAF in causing changes in airway reactivity is warranted. .A Hopp RJ; Bewtra AK; Nabe M; Agrawal DK; Townley RG. .I 274863 .U 91005417 .S Chest 9101; 98(4):942-4 .M Adolescence; Bronchoscopy; Child; Child, Preschool; Female; Human; Infant; Larynx/*AB; Male; Respiratory Sounds/ET; Retrospective Studies. .T Laryngomalacia in children. .P JOURNAL ARTICLE. .W Two hundred three (68 percent) of 297 children with laryngomalacia had associated respiratory disorders by flexible fiberoptic bronchoscopy (FFB). Associated disorders included congenital respiratory anomalies, a variety of anatomic obstructions of the upper and lower airways, and aspiration disorders. Mean age for isolated laryngomalacia (type 1) was 11.5 weeks (range, 5 weeks to 4 months) while children with laryngomalacia and associated respiratory disorders (type 2) had a mean age of 9.06 years (range, 6 weeks to 18 years). We conclude the following: (1) complete evaluation of the pediatric airways (bronchoscopy) is recommended in every symptomatic child with diagnosis of laryngomalacia confirmed by laryngoscopy; (2) type 1 laryngomalacia was more common in early infancy while type 2 laryngomalacia was associated with older age; (3) although type 2 laryngomalacia is the most common endoscopic diagnosis in our experience, the majority of cases were associated with lower airway dysfunction. .A Nussbaum E; Maggi JC. .I 274864 .U 91005418 .S Chest 9101; 98(4):945-8 .M Adult; Aged; Bronchial Neoplasms/*/PA/RA/TH; Case Report; Female; Human; Male; Myoblastoma/*/PA/RA/TH; Neoplasms, Multiple Primary/*/PA/RA/TH. .T Multicentric endobronchial granular cell myoblastoma. .P JOURNAL ARTICLE. .W Granular cell myoblastoma (GCM) is a rare benign neoplasm involving the tracheobronchial tree. It is believed to arise from the Schwann cell. Four cases of tracheobronchial GCM, all of which were multicentric, are presented and a conservative therapeutic approach is suggested. .A Redjaee B; Rohatgi PK; Herman MA. .I 274865 .U 91005419 .S Chest 9101; 98(4):949-53 .M Adolescence; Adult; Aged; Blood Pressure/DE; Dopamine/*TU; Epinephrine/*TU; Female; Fluid Therapy; Hemodynamics/*DE; Human; Lactates/BL; Male; Middle Age; Oxygen Consumption/*DE; Prospective Studies; Shock, Septic/DT/ME/*PP/TH. .T Effects of epinephrine on hemodynamics and oxygen metabolism in dopamine-resistant septic shock. .P JOURNAL ARTICLE. .W The hemodynamic effects of epinephrine were prospectively studied in 13 patients with septic shock who remained hypotensive after both fluid loading and dopamine. Hemodynamic measurements were performed before and one hour after the start of epinephrine infusion. Systolic, diastolic, and mean arterial pressure increased in all patients (p less than 0.01). Cardiac index and systemic vascular resistance increased by 34 and 32 percent, respectively (p less than 0.05), but heart rate and pulmonary vascular resistance remained unchanged. There was a concomitant increase in oxygen delivery (p less than 0.01) and oxygen consumption (p less than 0.05), the magnitude of the latter being related to baseline lactacidemia (p less than 0.01). In view of the generally recognized physiologic goals of septic shock management, we conclude that epinephrine could be an appropriate alternative where fluid loading and dopamine have failed. .A Bollaert PE; Bauer P; Audibert G; Lambert H; Larcan A. .I 274866 .U 91005420 .S Chest 9101; 98(4):954-8 .M Carboxyhemoglobin/AN; Catheterization/*IS; Comparative Study; Hemoglobins/AN; Human; Middle Age; Monitoring, Physiologic/IS; Oximetry/*IS; Respiratory Insufficiency/*BL/CO; Shock/*BL/CO; Spectrophotometry; Veins. .T Three mixed venous saturation catheters in patients with circulatory shock and respiratory failure [see comments] .P JOURNAL ARTICLE. .W Thirty-one critically ill patients with acute respiratory failure and circulatory shock were divided into three groups. Group 1 included 11 patients with an inserted mixed venous saturation (SvO2) catheter using three-reference wavelengths and characterized by one transmitting and one detecting fiberoptic filament (Oximetrix opticath catheter); group 2 included eight patients with an inserted SvO2 catheter using two-reference wavelengths and characterized by one transmitting and one detecting fiberoptic filament; (Edwards sat-one catheter); group 3 included 12 patients with an inserted SvO2 catheter using two-reference wavelengths and characterized by one transmitting and two detecting fiberoptic filaments. Once calibration procedures were performed, SvO2 measured by the catheter and by an hemoximeter OSM 3 (reference value) were compared following each therapeutic intervention. Over a period of 1.5 to 6 hours during which the hematocrit value remained unchanged, 119 measurements were obtained in group 1, 91 in group 2 and 181 in group 3. The dispersion of SvO2 values was much more pronounced with the two-reference wavelength systems using either one or two detecting fiber optic filaments, and the correlation coefficient was significantly higher with the three-reference wavelength system (r = 0.970 for the Oximetrix catheter vs r = 0.855 for the Edwards catheter and r = 0.826 for the Spectramed catheter, p less than 0.001). After 24 hours, the spontaneous drifts in the two-reference wavelength systems, using either one or two detecting fiber optic filaments (expressed as the SvO2 value measured by the catheter minus the reference SvO2 value) were significantly higher than the spontaneous drift in the three-reference wavelength system (9.3 +/- 7 percent for the Edwards catheter and +/- 6 +/- 4.1 percent for the Spectramed catheter vs 3.3 +/- 3.1 percent for the Oximetrix catheter, p less than 0.05). This study shows that a three-wavelength system is more accurate than a two-wavelength system for measuring acute changes in SvO2. The addition of a second detecting fiber optic filament does not seem to improve the accuracy of the system when SvO2 changes occur in conditions of stable hematocrit. .A Rouby JJ; Poete P; Bodin L; Bourgeois JL; Arthaud M; Viars P. .I 274867 .U 91005421 .S Chest 9101; 98(4):959-62 .M Human; Lactates/*BL; Oxygen/*BL; Oxygen Consumption/*; Positive-Pressure Respiration; Pulmonary Gas Exchange; Respiratory Distress Syndrome, Adult/BL/*ME/TH. .T Lactate levels as predictors of the relationship between oxygen delivery and consumption in ARDS. .P JOURNAL ARTICLE. .W We reviewed the changes in Do2 and Vo2 in 58 patients with ARDS after interventions which included fluid loading, blood transfusion, and PEEP. After a significant change in Do2, patients with lactic acidosis (lactate level greater than 2.4 mmol/L) exhibited significant corresponding changes in Vo2 (p less than 0.001); however, no change in Vo2 was observed in patients without lactic acidosis (1-beta greater than 0.8). We conclude that a biphasic pattern of oxygen utilization in patients with ARDS emerges when subsets of patients with and without lactic acidosis are compared. Lactic acidosis, a marker of anaerobic metabolism, may be a characteristic of patients with ARDS who exhibit changes in Vo2 that are dependent on changes in Do2. .A Kruse JA; Haupt MT; Puri VK; Carlson RW. .I 274868 .U 91005422 .S Chest 9101; 98(4):963-4 .M Asbestosis/*PA/PP; Human; Pleura/PA; Pleural Diseases/PA. .T What is asbestosis? .P JOURNAL ARTICLE. .A Smith DD. .I 274869 .U 91005423 .S Chest 9101; 98(4):965-72 .M Asbestosis/PA/*PP/RA; Forced Expiratory Flow Rates; Forced Expiratory Volume; Human; Lung Volume Measurements; Male; Middle Age; Pleura/*PA/RA; Respiratory Mechanics/*; Smoking/AE. .T Pulmonary functional impairment associated with pleural asbestos disease. Circumscribed and diffuse thickening. .P JOURNAL ARTICLE. .W To define the pulmonary functional impairment associated with pleural asbestos signs (PAS), we compared 738 men with only circumscribed (plaques) or diffuse pleural thickening on chest roentgenograms but no irregular opacities by ILO pneumoconiosis criteria (1980) with 738 age-matched asbestos-exposed men without any roentgenographic signs and with 228 men unexposed to asbestos. All men were white. Spirometry and total thoracic gas volumes (TGV) were measured and expressed as percentage of predicted of white Michigan men who have been modeled for spirometric values thereby adjusting for height, age, and in current and ex-smokers for duration of smoking. Asbestos-exposed men who never smoked had reduced FEF75-85 (p less than 0.01) and increased TGV (p less than .0001) as compared with unexposed men. The 155 men with PAS who had never smoked had reduced flows (p less than .0001), FVC (p less than 0.0056), and TGV (p less than .0001) when compared with 155 age-matched asbestos-exposed men. The 325 asbestos-exposed current smokers with normal chest roentgenograms compared with unexposed smokers had reduced expiratory airflows (p less than 0.0001), reduced FEV1 (p less than 0.004), and increased TGV (p less than 0.0001). The 325 current smokers with PAS had additional air trapping that further reduced vital capacity. Thus, PAS were associated with significant pulmonary dysfunction in men who never smoked, and current and ex-smokers had additional dysfunction even after adjustment for duration of smoking. .A Kilburn KH; Warshaw R. .I 274870 .U 91005424 .S Chest 9101; 98(4):973-9 .M Airway Obstruction/CO; Atelectasis/TH; Human; Lung/PP; Pulmonary Edema/DI/*ET/PP; Thoracostomy/AE. .T "Mechanical" causes of pulmonary edema. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .A Timby J; Reed C; Zeilender S; Glauser FL. .I 274871 .U 91005425 .S Chest 9101; 98(4):980-6 .M Absorption; Aged; Aged, 80 and over; Aging/ME/PH; Biological Availability; Cardiovascular Agents/AE/*PK; Human; Middle Age. .T Cardiovascular drugs in the elderly. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .A Abrams WB. .I 274872 .U 91005426 .S Chest 9101; 98(4):987-8 .M Air; Case Report; Diagnosis, Differential; Hernia/*RA; Human; Lung Diseases/*RA; Male; Middle Age; Neck/*RA. .T Air in the neck. .P JOURNAL ARTICLE. .A Li C; Miller WT. .I 274873 .U 91005427 .S Chest 9101; 98(4):989-93 .M Acute Disease; Cell Division/PH; Fibrosis/PA/PP; Growth Substances/*PH; Human; Lung/PA/*PP; Lung Diseases/PA/*PP. .T Failure of lung repair following acute lung injury. Regulation of the fibroproliferative response (Part 2). .P JOURNAL ARTICLE. .A Snyder LS; Hertz MI; Harmon KR; Bitterman PB. .I 274874 .U 91005428 .S Chest 9101; 98(4):994-8 .M Animal; Catheterization/*IS/MT; Dogs; Pulmonary Artery/RA; Pulmonary Embolism/RA/*TH. .T Mechanical disruption of pulmonary emboli in dogs with a flexible rotating-tip catheter (Kensey catheter). .P JOURNAL ARTICLE. .W Pulmonary embolism was induced in 11 dogs by the injection of three- to four-day-old allogeneic blood clots. The clots were made radiopaque by soaking them in contrast material. The resulting clots were firm, 3 to 4 cm long, and 1 cm in diameter. Injection of the clots into the external jugular vein consistently produced occlusion of at least one of the lobar pulmonary arteries. In every instance in which the tip of the catheter could be positioned at the clot embolus (six dogs), the clots were readily fragmented with a number 8 French (2.67 mm OD) flexible rotating tip catheter (Kensey catheter) activated at 80,000 rpm. Overall perfusion was shown by posttreatment angiograms to be markedly improved. These studies show that catheter-tip fragmentation of pulmonary emboli with a Kensey catheter has excellent potential for therapeutic application in patients with pulmonary embolism. .A Stein PD; Sabbah HN; Basha MA; Popovich J Jr; Kensey KR; Nash JE. .I 274875 .U 91005429 .S Chest 9101; 98(4):999-1005 .M Animal; Blood Pressure/DE; Cardiac Output/*DE; Cerebrovascular Circulation/DE; Comparative Study; Coronary Circulation/DE; Dogs; Epinephrine/*PD; Heart Massage; Hemodynamics/DE; Methoxamine/*PD; Resuscitation; Vascular Resistance/DE; Ventricular Fibrillation/MO/*PP/TH. .T The effects of methoxamine and epinephrine on survival and regional distribution of cardiac output in dogs with prolonged ventricular fibrillation [see comments] .P JOURNAL ARTICLE. .W This study compares the effects of methoxamine, a pure alpha 1-agonist, and epinephrine on cerebral and myocardial blood flow, central hemodynamics, and survival in a randomized placebo-controlled fashion during prolonged ventricular fibrillation (VF) in a canine model. Twenty-four anesthetized and ventilated adult mongrel dogs were instrumented for regional blood flow determinations using radio-labeled microspheres. The dogs were randomized to receive either 20 mg of methoxamine as a single intravenous bolus or repeated boluses of 0.02 mg/kg of epinephrine, 0.2 mg/kg of epinephrine, or normal saline solution placebo beginning at three minutes following induction of VF and initiation of closed chest cardiac massage (CCCM). Organ blood flow measurements were determined during normal sinus rhythm and after five and 20 minutes of VF. All six dogs receiving methoxamine were successfully resuscitated in contrast to only one in each of the epinephrine-treated groups and none of the dogs receiving placebo (p less than .01). Although epinephrine was associated with significantly higher blood pressures than placebo during cardiopulmonary resuscitation (CPR), blood pressures achieved with methoxamine were significantly higher than those observed in the other three treatment groups (p less than .001). Cerebral blood flow was significantly higher with both methoxamine and high-dose epinephrine (p less than .05). Mean left and right ventricular myocardial flows were highest with methoxamine but this did not achieve statistical significance. In contrast, organ flows measured in the animals receiving the lowest dose of epinephrine were not significantly higher than those associated with placebo. Cardiac output after 20 minutes of CPR was significantly lower with high-dose epinephrine than with methoxamine or placebo (p less than .05). Our results suggest that methoxamine significantly improves regional cerebral blood flow and survival during CPR and although high-dose epinephrine is associated with comparable improvements in regional cerebral blood flow, this treatment is associated with deterioration in central hemodynamics during prolonged VF and does not enhance survival. .A Roberts D; Landolfo K; Dobson K; Light RB. .I 274876 .U 91005625 .S Dis Colon Rectum 9101; 33(10):823-8 .M Adenocarcinoma/MO/*RT/SU; Combined Modality Therapy; Female; Follow-Up Studies; Human; Male; Methods; Neoplasm Recurrence, Local; Prognosis; Prospective Studies; Rectal Neoplasms/MO/*RT/SU; Recurrence; Statistics; Survival Rate. .T Preoperative radiotherapy in operable rectal cancer. .P CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL. .W The effect of preoperative radiotherapy (31.5 Gy in 3.5 weeks) in operable rectal cancer was examined with respect to resectability and prognosis after two surgical procedures, abdominoperineal resection, or low anterior resection. Preoperative radiation did not influence the surgeon's selection of low anterior resection, which was similar (40 percent) in each group. Radiation improved five-year survival probability and decreased the incidence of local recurrence significantly after low anterior resection. In contrast, no improvement of treatment results was found in patients treated by abdominoperineal resection after radiotherapy. .A Horn A; Halvorsen JF; Dahl O. .I 274877 .U 91005626 .S Dis Colon Rectum 9101; 33(10):829-35 .M Adult; Anastomosis, Surgical; Anus/SU; Body Water/ME; Colitis, Ulcerative/PP/SU; Electrolytes/ME; Female; Food; Gastrointestinal Motility/*; Human; Ileostomy; Ileum/*PP/SU; Intestinal Absorption/*; Male; Middle Age; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Time Factors. .T Absorption and motility of the bypassed human ileum. .P JOURNAL ARTICLE. .W The authors assessed absorption and motility of the human ileum after a prolonged period of disuse. In eight patients with ulcerative colitis, a manometric-catheter assembly was placed via the ileostomy into the unused portion of distal ileum two months after ileal pouch-anal anastomosis and temporary diverting loop ileostomy. The distal ileum was perfused at 5 ml/min with an isosmotic solution of either sodium chloride or ileal chyme diluted with sodium chloride for three hours before and three hours after a meal on two consecutive days. Absorption was measured, single and clustered pressure waves were identified and quantitated with the aid of a computer program, and a motility index was calculated. Mean absorption +/- S.E.M. of both perfusates was poor on day 1 (-10 +/- 2 ml/25 cm x 30 min), and the meal induced no ileal motor response. By day 2, however, absorption of both perfusates was much improved (-1 +/- 2 ml/25 cm x 30 min; P less than 0.05), and the number of discrete clustered contractions and the motility index now clearly increased after the meal (2.6 +/- 0.6 vs. 7.2 +/- 1.0 clustered waves/hr; 7.5 +/- 0.5 vs. 9.7 +/- 0.2 motility units/30 min; P less than 0.05). The conclusion was that absorption and motility of the human ileum were impaired after two months of disuse, but that ileal absorption and motility improved one day after the introduction of isosmotic ileal perfusates. .A Miedema BW; Karlstrom L; Hanson RB; Johnson GP; Kelly KA. .I 274878 .U 91005627 .S Dis Colon Rectum 9101; 33(10):836-9 .M Appendix; Cecal Diseases/DI; Cecum/*PA; Chi-Square Distribution; Colonoscopy; Female; Human; Intestinal Mucosa/PA; Male; Middle Age; Prospective Studies. .T The freckle sign--an endoscopic feature of the cecum. .P JOURNAL ARTICLE. .W Mucosal spots, or "freckles," surrounding the appendiceal orifice are an endoscopic feature of the cecum. These are clusters of 1 to 2 mm round or oval slightly raised spots, each with a pale center and an erythematous border. They correlate microscopically with subepithelial and submucosal lymphoid follicles. The freckling pattern, identified in about one third of colonoscopies, was seen best with the videoendoscope and was identified more commonly in patients with systemic illness. Recognition of mucosal freckling around the appendiceal orifice helps identify the cecum and may be useful in the evaluation of cecal and appendiceal pathology. .A Fleshner PR; Ackroyd FW; Shellito PC. .I 274879 .U 91005628 .S Dis Colon Rectum 9101; 33(10):840-5 .M Adult; Aged; Colorectal Neoplasms/*BL/BS/ME/PA; Dinoprostone/*BL/ME; Female; Human; Liver Neoplasms/*SC; Lung Neoplasms/*SC; Male; Middle Age; Support, Non-U.S. Gov't. .T Relationship between blood plasma prostaglandin E2 and liver and lung metastases in colorectal cancer. .P JOURNAL ARTICLE. .W The relationship of prostaglandin E2, of which a large amount is produced in various neoplasms, and hematogenous distant metastases was investigated in a total of 44 colorectal cancer patients because of its varied pathophysiologic potentials. The authors found significantly high levels of PGE2 in local venous blood draining the carcinoma and in peripheral blood in cases with liver or lung metastasis, as well as a significantly large amount of PGE2 production in the carcinoma tissue. The results suggest that increased local blood PGE2 could enhance the metastasis formation, and increased peripheral blood PGE2 may be useful in the detection of such metastasis in colorectal cancer. .A Narisawa T; Kusaka H; Yamazaki Y; Takahashi M; Koyama H; Koyama K; Fukaura Y; Wakizaka A. .I 274880 .U 91005629 .S Dis Colon Rectum 9101; 33(10):846-50 .M Adult; Aged; Aged, 80 and over; Colorectal Neoplasms/MO/PA/*SU; Female; Human; Male; Middle Age; Neoplasm Invasiveness; Neoplasm Metastasis; Palliative Treatment/*; Postoperative Complications/MO; Reoperation; Survival Rate. .T Palliative operations for colorectal cancer. .P JOURNAL ARTICLE. .W A review of 96 consecutive patients who underwent palliative surgery for primary colorectal cancer was undertaken to clarify the value of palliation achieved with surgical treatment. The overall rate of postoperative mortality was 8 percent (8 of 96) and the overall rate of postoperative morbidity was 24 percent (23 of 96). The mortality rate was 5 percent (3 of 66) after resective surgery and 17 percent (5 of 30) after nonresective surgery. Three deaths were related to the malignant disease, three were related to the intra-abdominal infection, and two were related to formation of intestinocutaneous fistulas. Of the 8 patients who died, 1 had a tumor with local visceral involvement only and 7 had a tumor with more distant spread. Median survival was 10 months for all patients, 15 months for patients treated with resective surgery, and 7 months for nonresected patients. Five patients (5 percent) have survived for longer than 5 years. The median relief of preoperative cancer symptoms was 4 months (4 months after resective surgery and 1 month after nonresective surgery). Twenty-five patients have undergone second surgery. It is concluded that palliative resective surgery for colorectal cancer can improve patient comfort with an acceptable postoperative mortality rate when cancer growth is localized and in favorable cases with more distant spread, whereas nonresective surgery fails to achieve symptom relief. .A Makela J; Haukipuro K; Laitinen S; Kairaluoma MI. .I 274881 .U 91005630 .S Dis Colon Rectum 9101; 33(10):851-7 .M Adult; Aged; Chi-Square Distribution; Colorectal Neoplasms/DI; Female; Gastrointestinal Hemorrhage/*/EH/ET; Human; Male; Middle Age; Patient Acceptance of Health Care/*; Patient Education; Patients/*PX; Rectum; Regression Analysis; Social Support; Socioeconomic Factors; Support, Non-U.S. Gov't; Time Factors. .T Rectal bleeding. Patient delay in presentation. .P JOURNAL ARTICLE. .W Patient delay in presentation of rectal bleeding has been identified as a factor in delayed diagnosis among patients with colorectal cancer. The aim of this study was to identify demographic or psychological factors, or beliefs or behaviors related to delay in presentation of rectal bleeding. In 93 patients presenting with this symptom to their general practitioner, delay ranged from 0 to 249 days with a median of 7 days; 27 (29 percent) delayed more than 14 days. Delay was unrelated to age, sex, ethnic origin, competence in English, length of schooling, social status, availability of social support, measured psychologic traits, and to the belief that the cause might be cancer. The proportions delaying more than 14 days were statistically significantly elevated among those who were not worried by the bleeding (47 percent delayed); those who did not regularly look at their feces or the toilet paper after use (37 percent); and those who took some other action before presenting to their general practitioner (43 percent). .A Dent OF; Goulston KJ; Tennant CC; Langeluddecke P; Mant A; Chapuis PH; Ward M; Bokey EL. .I 274882 .U 91005631 .S Dis Colon Rectum 9101; 33(10):858-62 .M Animal; Colitis/*PP; Colon/*PP; Diarrhea/PP; Fatty Acids/ME; Human; Intestinal Absorption/*; Intestinal Mucosa/*PP; Nutrition/*PH; Starvation/PP. .T The starved colon--diminished mucosal nutrition, diminished absorption, and colitis. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Nutrition of colonic epithelial cells is mainly from short chain fatty acids (SCFAs) produced by bacterial fermentation in the colonic lumen. n-Butyrate contributes more carbon of oxidation to epithelial cells than glucose or glutamine from the vasculature. Incomplete starvation of colonic epithelial cells through lack of luminal SCFAs leads, in the short term, to mucosal hypoplasia with either diminished absorption or diarrhea. A chronic lack of SCFAs or complete organ starvation in conjunction with other factors leads to nutritional colitis, either "diversion colitis" or "starvation colitis." Whether predominantly diarrhea or colitis develops in mucosal malnutrition appears to depend upon the severity and duration of starvation. Ulcerative colitis may be classified as a nutritional colitis in that colonic epithelial cells are unable to utilize SCFAs reflecting epithelial starvation despite abundant SCFAs. .A Roediger WE. .I 274883 .U 91005632 .S Dis Colon Rectum 9101; 33(10):863-8 .M Acoustics; Comparative Study; Human; In Vitro; Lymph Nodes/*PA; Lymphatic Metastasis; Neoplasm Staging; Rectal Neoplasms/*PA; Rectum; Sensitivity and Specificity; Support, Non-U.S. Gov't; Ultrasonography/*. .T Endosonography of pararectal lymph nodes. In vitro and in vivo evaluation. .P JOURNAL ARTICLE. .W One hundred thirteen patients with carcinoma of the rectum were evaluated for lymph node metastases by endorectal ultrasound. With the use of 7.5 MHz and based on different echo patterns, two main groups of lymph nodes can be differentiated: hypoechoic and hyperechoic lymph nodes. Compared with pathologic findings, hypoechoic lymph nodes represent metastases, whereas hyperechoic lymph nodes are visualized due to unspecific inflammation. Lymph node metastases can be predicted with a sensitivity of 72 percent and inflammatory lymph nodes with a specificity of 83 percent. The physical basis of the differentiation of lymph nodes was assessed in vitro by the determination of ultrasound parameters (speed of sound, acoustic impedance, attenuation, and backscattered amplitude). The attenuation coefficient of benign lymph nodes [2.5 dB/(MHz x cm)] is significantly higher than the mean value of lymph node metastases [1.3 db/(MHz x cm)]. The results demonstrate that involved nodes can principally be differentiated from not involved nodes. Micrometastases, mixed lymph nodes, and changing echo patterns within inflammatory nodes explain the accuracy rate of 78 percent. .A Hildebrandt U; Klein T; Feifel G; Schwarz HP; Koch B; Schmitt RM. .I 274884 .U 91005633 .S Dis Colon Rectum 9101; 33(10):869-73 .M Adult; Crohn Disease/*/DT/PP/SU; Female; Fertilization; Human; Pregnancy; Pregnancy Complications/*/DT/PP/SU; Pregnancy Outcome/*; Prognosis; Recurrence; Retrospective Studies; Support, Non-U.S. Gov't. .T Crohn's disease and pregnancy. .P JOURNAL ARTICLE. .W Seventy-eight pregnancies in 50 patients were reviewed to evaluate the effects of Crohn's disease on the outcome of pregnancy and the influence of the pregnancy on the course of Crohn's disease. Overall, 21 pregnancies (27 percent) had abnormal outcomes including spontaneous abortions (9), infants small for gestational age (6), premature infants (5), and infants who developed respiratory distress (1). Eight (50 percent) patients with active disease compared with 13 (21 percent) patients with inactive disease at conception had abnormal outcomes (P less than 0.05). During pregnancy 15 (55 percent) with active disease and 6 (12 percent) with inactive disease had an abnormal outcome (P less than 0.001). Neither medical nor surgical treatment, independent of disease activity, appeared to affect the outcome adversely. Eighteen of 73 (25 percent) patients with quiescent or mild disease relapsed, and seven of 16 patients with some disease activity improved (44 percent). Of 34 patients on medication, nine relapsed (27 percent), and of 39 patients not on medication, nine relapsed (24 percent) (P = N.S.). These results suggest that the outcome of pregnancy is not adversely affected by Crohn's disease. However, patients with active disease at conception and/or during the pregnancy have poorer outcomes independent of the use of medication or requirement of surgery. Neither pregnancy nor medications taken affect the course of the disease. .A Woolfson K; Cohen Z; McLeod RS. .I 274885 .U 91005634 .S Dis Colon Rectum 9101; 33(10):874-7 .M Adult; Aged; Anus Neoplasms/*/EP/PA/SU; Female; Human; Incidence; Male; Melanoma/*/EP/PA/SU; Middle Age; Palliative Treatment; Prognosis; Rectal Neoplasms/*/EP/PA/SU; Recurrence; Survival Rate; Sweden/EP. .T Anorectal malignant melanoma in Sweden. Report of 49 patients. .P JOURNAL ARTICLE. .W Clinicopathologic features and prognosis of 49 patients with anal malignant melanoma were investigated in the total Swedish population between 1970 and 1984. Median age was 71 years (range, 50 to 87 years), and there was a female predominance (31 females, 18 males). The most common symptom at presentation was bleeding. The majority of tumors ranged between 2 and 5 cm in diameter and all invaded at least into the submucosa and/or the lamina propria. At diagnosis, one third of the patients had either regional or distant metastasis with a median survival of 5 months. The remaining patients were surgically treated with curative intent, either by abdominoperineal resection (APR) or local excision. Median survival was poor in both treatment groups (APR, 12 months; local excision, 13 months). Most patients died with distant metastasis. Our results confirm the opinion that APR offers no more curative potential than a more conservative surgical approach. However, tumor sizes were on average smaller in the group treated by local excision. This could indicate that, in the absence of known distant metastasis, radical surgery should be performed, particularly since local recurrences tended to be more common after a local excision. .A Goldman S; Glimelius B; Pahlman L. .I 274886 .U 91005635 .S Dis Colon Rectum 9101; 33(10):878-82 .M Aminoglycosides/*AD; Bacterial Infections/*PC; Ceftizoxime/*AD; Comparative Study; Drug Administration Schedule; Human; Incidence; Intestinal Diseases/MI/*SU; Metronidazole/*AD; Postoperative Complications/*PC; Premedication/*; Prospective Studies; Risk Factors; Surgical Wound Infection/PC. .T Short-term chemoprophylaxis with ceftizoxime vs. five-day aminoglycoside with metronidazole in 'contaminated' lower gastrointestinal surgery. .P CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL. .W In a prospective, open, randomized controlled trial, 173 patients requiring surgery for potentially "contaminated" lower gastrointestinal surgery were allocated to receive either two doses of ceftizoxime (2 gm) with one dose of metronidazole (1.5 gm) or gentamicin 3 mg/kg/day for five days with one dose of metronidazole (1.5 gm). Eighty-nine patients received ceftizoxime and 84 patients received gentamicin. The groups were comparable with respect to diagnosis, procedure, type of anastomosis, and wound closure. The incidence of withdrawal due to failure to respond to the study drug (11.5 percent) was equivalent in the two groups. There was no difference in the overall incidence of postsurgical infection between the ceftizoxime and metronidazole group (22.2 percent) and the gentamicin and metronidazole group (25.7 percent). The incidence of wound infection (ceftizoxime and metronidazole, 6.9 percent; gentamicin and metronidazole, 10 percent) and deep sepsis (ceftizoxime and metronidazole, 15.3 percent; gentamicin and metronidazole, 15.7 percent) was similar. .A Winslet MC; Youngs D; Burdon DW; Keighley MR. .I 274887 .U 91005636 .S Dis Colon Rectum 9101; 33(10):883-5 .M Adult; Case Report; Female; Human; Intestines/*AB/BS/SU; Mesenteric Veins/*AB/SU; Rotation. .T Reversed intestinal rotation associated with anomalous mesenteric venous drainage. Report of a case. .P JOURNAL ARTICLE. .W Reverse intestinal rotation is a congenital abnormality of midgut rotation. Mesenteric arterial, venous, and lymphatic compression may occur, but associated anomalous mesenteric venous drainage is extremely rare. The case presented illustrates the importance of recognition of intestinal malrotation and the danger of bowel resection in the presence of anomalous mesenteric venous drainage. .A O'Connell PR; Lynch G. .I 274888 .U 91005637 .S Dis Colon Rectum 9101; 33(10):886-9 .M Adult; Aged; Aged, 80 and over; Anus Diseases/DI/EP; Diagnosis, Differential; Female; Human; Incidence; Male; Middle Age; Tuberculosis, Gastrointestinal/CO/*DI/DT. .T Gastrointestinal tuberculosis. Report of four cases. .P JOURNAL ARTICLE. .W Gastrointestinal tuberculosis is a rare disease in the United States. Correct identification is often delayed because it is not considered early on in the differential diagnosis. Four patients with gastrointestinal tuberculosis and the symptoms, diagnosis, complications, and treatment of the disease are discussed. Gastrointestinal tuberculosis should be considered in Asian immigrant patients who present with symptoms and signs of inflammatory bowel disease. .A Abel ME; Chiu YS; Russell TR; Volpe P. .I 274889 .U 91005638 .S Dis Colon Rectum 9101; 33(10):891-901 .M Anastomosis, Surgical; Animal; Biomechanics; Collagen/ME; Intestines/PH/*SU; Surgical Wound Dehiscence/ET/PP; Tensile Strength; Wound Healing/*. .T Healing of experimental intestinal anastomoses. Parameters for repair. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Anastomotic dehiscence remains a major complication in surgery of the large bowel, and studies on the healing sequence of experimental anastomoses are necessary to define underlying mechanisms and find ways to improve surgical outcome, particularly in high-risk situations. For the quantitative description of anastomotic repair, both mechanical and biochemical parameters are employed, each with their own limitations. Mechanical parameters, either bursting pressure or breaking strength, only reflect growing anastomotic strength as long as disruption occurs within the anastomotic area, which is less than one week after surgery for the bursting pressure and probably up to two weeks for the breaking strength. The biochemical description of anastomotic repair has been limited to behavior of collagen, as represented by its rather unique constituent amino acid hydroxyproline. Conclusions based on collagen concentrations--per unit weight--should be considered with caution since they may change as a consequence of changes in noncollagenous substances. In this respect, collagen content, per unit length, is probably a better parameter to describe anastomotic collagen levels. Few investigations have addressed the quality of collagen (e.g., crosslinking or type). Since, at this time, no distinct correlations have been demonstrated between development of mechanical strength or occurrence of leakage and collagen levels in the healing anastomosis, attention should not be restricted to a description of the quantity of collagen present: the quality of anastomotic collagen should be investigated, perhaps even more so. .A Hendriks T; Mastboom WJ. .I 274890 .U 91005639 .S Dis Colon Rectum 9101; 33(10):902 .M Appendix/*SU; Child; Foreign Bodies/*SU; Human; Methods. .T Foreign body removal through an appendicostomy. .P JOURNAL ARTICLE. .W The removal of button cell batteries or small coins impacted in the terminal ileum or right colon through an appendicostomy is described. This technique was used effectively in three patients. .A Mizrahi S; Eyal I; Shtamler B. .I 274891 .U 91005640 .S Dis Colon Rectum 9101; 33(10):903-4 .M Anus/*SU; Hemorrhoids/*SU; Human; Intestinal Mucosa/*SU; Surgical Flaps/*MT. .T Surgical treatment of circumferential hemorrhoids. .P JOURNAL ARTICLE. .A Selvaggi F; Scotto di Carlo E; Silvestri A; Notaroberto A; Maffettone V. .I 274892 .U 91005641 .S Dis Colon Rectum 9101; 33(10):905-6 .M Diverticulitis, Colonic/*SU; Human; Mesenteric Arteries/SU; Mesenteric Veins/SU; Methods; Sigmoid/SU; Sigmoid Diseases/*SU. .T A safe technique for resection of perforated sigmoid diverticulitis. .P JOURNAL ARTICLE. .A Abcarian H; Pearl RK. .I 274893 .U 91005642 .S Dig Dis Sci 9101; 35(10):1185-9 .M Adolescence; Adult; Barrett Esophagus/CO/*EP/PA; Child; Child, Preschool; Female; Human; Incidence; Male; Mental Retardation/CO/EP; Retrospective Studies; Risk Factors. .T Barrett's esophagus in children and young adults. Frequent association with mental retardation. .P JOURNAL ARTICLE. .W Since few data are available on epidemiologic features of Barrett's esophagus in young persons, we reviewed the case records of patients undergoing esophageal biopsies at Children's Hospital, Boston, from 1982 through 1986. There were 1423 esophageal biopsies obtained from 1173 patients, and histological evidence of esophagitis was present in 397 cases; Barrett's epithelium was diagnosed in 10 patients (0.9% of total and 2.5% of esophagitis cases). Specialized columnar epithelium was present in seven of these 10 patients. The mean age of those with Barrett's epithelium was 19.0 +/- 7.9 years (range 3.7-27 years) compared to 8.7 +/- 6.7 years (range 4 days to 31 years) for all patients biopsied (P less than 0.0001); 80% (8/10) of the Barrett's cases were male compared to 54% of all cases. The relative importance of the possible risk factors was assessed by comparing the 10 patients with Barrett's with the 541 patients that had esophageal biopsies in calendar years 1984-1985. Mental retardation, a risk factor not previously described for young persons with Barrett's esophagitis, was present in 70% (7/10) of the Barrett's patients but in only 15% of all patients biopsied (P less than 0.0002). The frequency of mental retardation was also higher, but not significantly so (P greater than 0.07), in patients with biopsies that were positive for esophagitis (19%) than in those with normal biopsies (14%). No significant differences were found between the Barrett's group and all patients biopsied in regards to racial origin, prior stricture, or fundoplication. .A Snyder JD; Goldman H. .I 274894 .U 91005643 .S Dig Dis Sci 9101; 35(10):1190-7 .M Acid-Base Equilibrium/PH; Adult; Circadian Rhythm/*PH; Esophagus/*PH; Female; Human; Male; Manometry; Middle Age; Monitoring, Physiologic; Peristalsis/PH; Reference Values; Support, Non-U.S. Gov't. .T Twenty-four-hour pattern of esophageal motility in asymptomatic volunteers. .P JOURNAL ARTICLE. .W Diurnal variations in the pattern of esophageal motility and acidity were studied in 14 healthy volunteers. Data from a two-channel manometry and one-channel pH-metry recording were stored in a portable 1-MByte, solid-state data logger for subsequent computerised analysis. Comparison of predefined nighttime, mealtime and nonmeal daytime periods showed that propagated contractions predominated during mealtimes (56% of all contractions) and nonmeal daytime periods (53.5% of contractions) and that their propagation velocity (2.98 cm/sec) was at its lowest and the AUC of all contractions (134.6 hectoPascal.sec) at its greatest during mealtime periods. During the night, propagated contractions (0.136/min) and simultaneous contractions (0.025/min) were significantly less frequent than during both meal (1.31/min and 0.172/min, respectively) and nonmeal daytimes (0.665/min and 0.133/min, respectively), whereas the nocturnal segmental contraction frequency (0.181/min) was not significantly lower than the nonmeal daytime contraction frequency (0.243/min). Median reflux time was in the normal range (1.2%), although two subjects had prolonged reflux times (9.5% and 14.5%). In conclusion, all subjects showed similar patterns of diurnal esophageal contractory activity determined partly by meal intake and partly by a characteristic clustering of nocturnal contractions that could not be explained by episodes of nocturnal gastroesophageal reflux. It may, therefore, be speculated that nocturnal contraction clusters are associated with rhythmic phenomena such as MMC or specific sleep stages. .A Armstrong D; Emde C; Bumm R; Castiglione F; Cilluffo T; Blum AL. .I 274895 .U 91005644 .S Dig Dis Sci 9101; 35(10):1198-204 .M Adult; Aged; Deglutition/*PH; Deglutition Disorders/PP/*RI; Female; Gastrointestinal Transit/PH; Human; Male; Middle Age; Neuromuscular Diseases/PP; Oropharynx/PH/*RI; Reproducibility of Results; Technetium Tc 99m Sulfur Colloid/*DU. .T Scintigraphic measurement of oropharyngeal transit in man. .P JOURNAL ARTICLE. .W Scintigraphic studies of the oropharyngeal transit of a liquid bolus were performed in 15 healthy controls, 12 patients with symptoms of oral-pharyngeal dysphagia, and 13 patients with neuromuscular disease, who did not have dysphagia. Gamma camera imaging of the head, neck, and upper thorax was undertaken, in the lateral projection, during the swallowing of the radiolabeled bolus of water. Inspection of summed images permitted the selection of regions of interest (ROI) to represent the mouth, pharynx, and upper esophagus. Transit times between each ROI were calculated and compared. Significant prolongation of bolus transit time between the mouth and esophagus was present in both patients with and without dysphagia (0.59 +/- 0.38 sec and 0.33 +/- 0.7 sec; mean +/- SD, respectively) compared with controls (0.26 +/- 0.04 sec P less than 0.001, P less than 0.01, respectively, Mann-Whitney U test). Repeat studies in 25 individuals indicated that the transit measurements were more reproducible between swallows in normal subjects than in patients with symptoms. Deglutitive scintigraphy provides a noninvasive technique for the quantitative study of swallowing and its disorders. .A Holt S; Miron SD; Diaz MC; Shields R; Ingraham D; Bellon EM. .I 274896 .U 91005645 .S Dig Dis Sci 9101; 35(10):1205-10 .M Animal; Ascorbic Acid/TO; Aspirin/TO; Delayed-Action Preparations; Doxycycline/AA/TO; Esophagus/*DE/PA; Ferrous Compounds/TO; Ibuprofen/TO; Potassium Chloride/TO; Rabbits; Support, Non-U.S. Gov't. .T Drug-induced esophageal injury. Histopathological study in a rabbit model. .P JOURNAL ARTICLE. .W The purpose of this animal study was to investigate the histopathologic consequences of esophageal exposure to a variety of medications known to be injurious to the human esophagus. Twenty-four New Zealand white rabbits were utilized. Tablets or control plastic beads were secured to a silk suture thread and positioned in the rabbit esophagus through a proximal esophagostomy and a gastrostomy. Test medications were allowed to dissolve passively on the surface of the esophageal mucosa in the anesthetized rabbits. After 1 hr of drug exposure, the rabbits were killed and the esophagus removed and examined. No gross abnormalities were detected with the exception of a mild degree of erythema at some of the exposure sites. All medications and control beads produced microscopic mucosal changes when compared to suture controls. The beads and test medications caused thinning of the epithelium and increased subepithelial edema (P less than 0.05). Two changes, however, were unique to animals exposed to test medications: fraying and/or splitting of the epithelium and the presence of balloon cells (P less than 0.05). Balloon cells represent damaged squamous epithelial cells recognizable by their distended, globoid shape. The prevalence of balloon cells ranged from 22% to 89% of sites exposed to drug and was most commonly associated with potassium. Of all drugs reported to cause injury to the human esophagus, potassium chloride has been reported to produce the most severe lesions, including esophageal stricture and perforation.(ABSTRACT TRUNCATED AT 250 WORDS) .A Brewer AR; Smyrk TC; Bailey RT Jr; Bonavina L; Eypasch EP; Demeester TR. .I 274897 .U 91005646 .S Dig Dis Sci 9101; 35(10):1211-6 .M Animal; Antacids/*TU; Duodenitis/*EN/PA/*TH; Male; Milk/*; Myeloperoxidase/*ME; Neutrophils/PA; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; 16,16-Dimethylprostaglandin E2/*TU. .T Effects of milk, prostaglandin, and antacid on experimentally induced duodenitis in the rat. Use of myeloperoxidase as an index of inflammation. .P JOURNAL ARTICLE. .W Ulcerogenesis of the duodenal mucosa frequently involves an inflammatory reaction with infiltration of leukocytes. Measurement of neutrophil myeloperoxidase activity might thus be a sensitive indicator of damage, before visible lesions occur. To test this possibility, a rat model for duodenal injury was used where fasted animals were treated with indomethacin and histamine-diHCl. Twenty-four hours after indomethacin treatment, duodenal tissues were collected for histochemical staining and biochemical assay for myeloperoxidase activity. Indomethacin- and histamine-challenged rats had significantly elevated myeloperoxidase activity compared to unchallenged controls (P less than 0.05) for both histochemistry and biochemistry. There was also a significant correlation between these two parameters (r = 0.68, P less than 0.001). The duodenal injury model then was used to test the effectiveness of known gastric protective agents. Results indicated that milk and buttermilk did not aggravate or protect against duodenal injury, while antacid and prostaglandin did significantly protect against inflammation (P less than 0.02). We concluded that measurement of myeloperoxidase activity is a sensitive and potentially useful estimate of duodenal injury that can be valuable in assessing ulcerogenesis and healing. .A Cooper LC; Dial EJ; Lichtenberger LM. .I 274898 .U 91005647 .S Dig Dis Sci 9101; 35(10):1217-25 .M Animal; Bromodeoxyuridine/DU; Cell Separation/MT; DNA/*DE; Gastric Mucosa/CY/*DE/PA; Hydrogen-Ion Concentration; In Vitro; Male; Necturus; Omeprazole/*TO; Rats; Rats, Inbred Strains. .T Cell isolation and genotoxicity assessment in gastric mucosa. .P JOURNAL ARTICLE. .W It has been claimed that in vitro digestion of in vivo DNA-labeled gastric mucosa is suitable for evaluation of genotoxic effects of drugs or chemicals. This method was then used to show that omeprazole (a novel antiulcer drug) was potentially genotoxic. In this study we have examined the method used and the interaction of omeprazole and its derivatives with purified DNA. The method was shown to enrich for dividing cells (6.92 +/- 0.693%, N = 43, 2-hr labeling) in the digest from the intact tissue and was therefore unsuitable for estimating unscheduled DNA synthesis in the gastric mucosa induced by chemicals or drugs including omeprazole. It was further shown that neither omeprazole or its acid-activated product, a cationic sulfenamide, were able to react with isolated purified DNA from either a prokaryote (E. coli) or a eukaryote (salmon sperm). Hence any conclusions using this method attributing acute genotoxic effects to any chemical are based on unrecognized artifacts of the technique and are unsound. In addition, these results negate the suggestion that omeprazole or its gastric metabolites are genotoxic. .A Scott D; Reuben M; Zampighi G; Sachs G. .I 274899 .U 91005648 .S Dig Dis Sci 9101; 35(10):1226-30 .M Adenocarcinoma/SU; Aged; Anastomosis, Surgical; Case Report; Duodenal Neoplasms/SU; Duodenum/*SU; Gastric Emptying/*PH; Gastrointestinal Motility/PH; Human; Male; Pancreatectomy/*AE; Postoperative Complications/*PP; Stomach Diseases/*ET/PP; Support, U.S. Gov't, Non-P.H.S.. .T Gastric dysrhythmias following pylorus-preserving pancreaticoduodenectomy. Possible mechanism for early delayed gastric emptying. .P JOURNAL ARTICLE. .W Transient delayed gastric emptying is reported as a frequent complication following pancreas-preserving pancreaticoduodenectomy (PPW). We placed serosal electrodes on the stomach of a patient undergoing PPW. Myoelectric recordings were obtained postoperatively and correlated with simultaneous radionuclide liquid gastric emptying studies. The patient developed early postoperative gastric atony, associated with frequent gastric dysrhythmias. These dysrhythmias may have been exacerbated by a perihepatic abscess. The gastric dysrhythmias correlated with alterations in liquid gastric emptying. Gastric dysrhythmias may be a mechanism for gastric dysfunction in the early postoperative period. .A Hocking MP; Harrison WD; Sninsky CA. .I 274900 .U 91005649 .S Dig Dis Sci 9101; 35(10):1231-8 .M Animal; Cholesterol/*PD; Drug Synergism; Gastric Mucosa/*DE; Lipids/PD; Male; Phospholipids/*PD; Rats; Rats, Inbred Strains; Sterols/PD; Stomach Ulcer/*PC; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Triglycerides/PD. .T Sterol-dependence of gastric protective activity of unsaturated phospholipids. .P JOURNAL ARTICLE. .W The major aim of this study was to investigate the gastric protective effect of unsaturated phospholipids and to determine the ability of neutral lipids to enhance this activity. We found that although a liposomal suspension of unsaturated phosphatidylcholine (PC) administered intragastrically failed to protect rats from acid-induced gastric ulcer formation, addition of cholesterol to unsaturated PC induced a dose-dependent protective response with the maximally effective dose, reducing lesion score greater than 70%. This effect also was seen with the plant sterol, beta-sitosterol (reducing lesion score by 81.6 +/- 36%) but was blocked if cholesterol was esterified to fatty acids of varying chain length. Addition of sterols to liposomes of saturated dipalmitoylphosphatidylcholine, in contrast, attenuated the gastric protective action of the saturated PC. It appears that the protective mechanism elicited by sterols and unsaturated PC is not mediated by alterations in gastric emptying rate or prostaglandin biosynthesis, although maintenance of surface hydrophobicity may be involved. These results suggest that the sterol may promote the packing of adjacent unsaturated phospholipid molecules of either the cell membrane or a putative extracellular hydrophobic lining of the gastric epithelium to provide the mucosa with protection against luminal acid. .A Romero JJ; Lichtenberger LM. .I 274901 .U 91005650 .S Dig Dis Sci 9101; 35(10):1239-43 .M Adult; Case Report; Female; Gastric Mucosa/*PA/SE; Human; Male; Prospective Studies; Pyloric Antrum/PA; Running/*; Stomach Diseases/*ET/PA. .T Gastric lesions secondary to long-distance running. .P JOURNAL ARTICLE. .W Gastrointestinal disorders have been reported during long-distance running. The purpose of this study was to evaluate the effects of prolonged exercise on the upper digestive tract. Seven subjects were submitted to a standard endoscopic examination of the upper digestive tract before and after long-distance running (range 18-50 km). Mucosal biopsy specimens were taken during all endoscopies. After running, all runners had histologically pathological features in the stomach. Vascular lesions were present in the chorion in six subjects after running, with the intensity of the lesions ranging from congestion to hemorrhage. Postexercise histological examination also showed a decrease in mucosal secretion. These lesions secondary to prolonged exercise indicate the presence of hemodynamic perturbations in the upper digestive tract. .A Gaudin C; Zerath E; Guezennec CY. .I 274902 .U 91005651 .S Dig Dis Sci 9101; 35(10):1244-8 .M Acid-Base Equilibrium/*PH; Animal; Duodenum/DE/*PH; Female; Gastric Acid/*PH; Intestinal Mucosa/DE/PH; Male; Rats; Rats, Inbred Strains; Secretin/PD; Somatostatin/PD; Support, Non-U.S. Gov't. .T Tolerance of rat duodenum to luminal acid. .P JOURNAL ARTICLE. .W The tolerance of the duodenal mucosa to luminal acid was investigated by measuring with a liquid sensor pH microelectrode technique the epithelial surface pH (pHs) and subepithelial tissue pH (pHt) in rat proximal (duodenal bulb, Brunner gland area) and distal duodenum exposed to luminal acid. Under basal conditions, pHs was roughly equal in both parts of the duodenum; proximal duodenum, 7.40 +/- 0.14 (mean +/- SEM) at the villus tip and 7.54 +/- 0.16 at the depth of crypt; distal duodenum, 7.46 +/- 0.19 and 7.55 +/- 0.09, respectively. Yet, exposure of the mucosa to luminal acid (10 mM HCl) provoked a significantly lesser decrease of pHs (0.25 +/- 0.13 vs 0.42 +/- 0.12 pH units) in the proximal duodenum, suggesting that the response of epithelial HCO3 secretion to luminal acid is stronger in that part of the duodenum. Further, the initial acidification of pHs was followed in the proximal duodenum by a secondary alkalinization of pHs, leading to normalization of pHs, which may suggest activation of compensatory protective mechanisms. pHt at the villus tip was likewise roughly equal in both parts of duodenum (7.29 +/- 0.05 vs 7.17 +/- 0.04), but, again, acidification of the luminal perfusate progressively from 10 to 100 mM HCl induced a much earlier and significantly more profound acidification in the distal than in the proximal duodenum. The possible contribution of Brunner glands to the greater mucosal tolerance to acid in the proximal duodenum was assessed by investigating whether stimulation or inhibition of Brunner gland secretion modulates the response of the duodenal mucosa to acid.(ABSTRACT TRUNCATED AT 250 WORDS) .A Paimela H; Kiviluoto T; Mustonen H; Sipponen P; Kivilaakso E. .I 274903 .U 91005652 .S Dig Dis Sci 9101; 35(10):1249-56 .M Adrenergic Alpha Receptor Agonists/*PD; Animal; Clonidine/*AA/PD; Dogs; Drug Interactions; Eating/PH; Gastrointestinal Motility/*DE; Injections, Intravenous; Injections, Spinal; Morphine/AI/*PD; Naloxone/PD; Phentolamine/PD; Propranolol/PD; Support, U.S. Gov't, P.H.S.. .T Demonstration of intrathecal and systemic morphine and ST-91 effects on fed canine upper gut motility. .P JOURNAL ARTICLE. .W We studied the effects of opioid and adrenergic agonists and antagonists given systemically intravenously and intrathecally on postprandial antral and small bowel motility in a chronic conscious dog model. We studied eight dogs with a surgically implanted thoracic spinal intrathecal injection catheter, and six gastrointestinal manometric perfusion catheters. Morphine given intrathecally or intravenously induced propagated clusters of intestinal pressure activity in the fed dogs. The minimal effective dose for morphine was 150 micrograms/kg by the intrathecal route and 450 micrograms/kg by the intravenous route. ST-91 (an alpha 2-adrenergic agonist) profoundly inhibited antral and small intestinal pressure activity with similar minimal effective dose (100 micrograms/kg) and duration of effect for both intravenous and intrathecal routes. Neither naloxone (3000 micrograms/kg) nor combined phentolamine (1500 micrograms/kg) with propranolol (300 micrograms/kg) altered postprandial antral or small intestinal motility. The capacity of pharmacologic agents to block morphine-induced activity fronts when administered in the same compartment (intravenously or intrathecally) was investigated. The minimally effective morphine-antagonist dose for naloxone was similar intrathecally and intravenously (36 micrograms/kg for both routes). ST-91 (100 micrograms/kg) when given intrathecally or intravenously blocked morphine-induced clustered phasic pressure activity while simultaneously abolishing postprandial small intestine phasic pressure activity. These data suggest the presence of opioid and alpha 2-adrenergic receptors in the spinal cord that can modulate gastrointestinal motility in the postprandial state. Pharmacological interactions between these systems occur at spinal and target organ levels. .A Thomforde GM; Malagelada JR; Camilleri M; Yaksh TL. .I 274904 .U 91005654 .S Dig Dis Sci 9101; 35(10):1265-70 .M Animal; Cholecystokinin/*BL; Circadian Rhythm/*DE/PH; Dietary Proteins/*PD; Female; Gastrins/*BL; Male; Rats; Rats, Inbred Strains; Sex Factors; Support, U.S. Gov't, P.H.S.. .T Effects of dietary protein alterations on circadian rhythms of gastrointestinal peptides in rats. .P JOURNAL ARTICLE. .W Altered protein diets and circadian rhythms of gastrin and cholecystokinin (CCK) were investigated in 126 male and 126 female Sprague-Dawley rats acclimated for two weeks to a 12:12 hr light-dark cycle. Rats were divided equally and fed low-protein (8%), high-protein (64%) or normal protein (27%) diets for four weeks. All animals were fasted for 24 hr prior to blood collections. Blood samples were collected at 4-hr intervals for 24 hr for determination of plasma gastrin and CCK using specific radioimmunoassays. A significant rhythm for gastrin was detected in males on normal and low-protein diets (P less than 0.03) and in females on low-protein diets (P less than .02). A significant rhythm for CCK was detected (P less than 0.05) in rats of both sexes fed normal and high-protein diets. Mean plasma levels of both peptides were lower in females than males. In a separate study, food intake and body weight were monitored in male rats receiving the three diets over 21 days. Animals on the low-protein diet exhibited reduced food intake and body weight compared to rats fed the normal or high-protein diets. .A Pasley JN; Rayford PL. .I 274905 .U 91005655 .S Dig Dis Sci 9101; 35(10):1271-5 .M Adaptation, Physiological; Adult; Colon/*PH; Conditioning (Psychology)/PH; Constipation/*PX; Defecation/PH; Gastrointestinal Transit/PH; Human; Male; Reference Values; Support, Non-U.S. Gov't. .T Behavioral modification of colonic function. Can constipation be learned? .P JOURNAL ARTICLE. .W We challenged the two hypotheses: first, that defecation can be suppressed for an extended time, and second, if so, that this has an effect on upper colonic motility. Thus we studied 12 male volunteers with conditions of identical nutrition and patterns of physical activity over a two-week period, where one week with normal defecation and one week with voluntary prolonged suppression of defecation followed each other in randomized order. Frequencies of defecation, stool weights, total and segmental colonic transit times (using radiopaque markers) were compared. Frequency of defecations and stool weights were lower during suppressed defecation [8.9 +/- 0.66 vs 3.7 +/- 0.41 (mean +/- SE) bowel movements per week, P = 0.003, and 1.30 +/- 0.09 vs 0.98 +/- 0.13 kg/week, P = 0.01]. Total transit times were increased from 28.8 +/- 4.4 to 53.1 +/- 4.3 hr, P = 0.004. Segmental transit times were increased in the rectosigmoid (from 8.83 +/- 3.6 to 32.1 +/- 5.6 hr, P = 0.04) and right hemicolon (from 14.5 +/- 0.9 hr to 19.7 +/- 1.5 hr, P = 0.02) by suppression of defecation. We conclude that defecation habits may induce changes in colonic function such as those seen in constipation and that functional anorectal outlet obstruction may, probably by reflex mediation, affect the right colon. .A Klauser AG; Voderholzer WA; Heinrich CA; Schindlbeck NE; Muller-Lissner SA. .I 274906 .U 91005656 .S Dig Dis Sci 9101; 35(10):1276-80 .M Adolescence; Adult; Aged; Aged, 80 and over; Alberta; Attitude to Health; Child; Colitis, Ulcerative/PX; Consumer Satisfaction; Crohn Disease/PX; Female; Health Status; Human; Inflammatory Bowel Diseases/*PX; Life Change Events; Male; Middle Age; Outpatient Clinics, Hospital/*UT. .T Outpatient health care utilization of patients with inflammatory bowel disease. .P JOURNAL ARTICLE. .W On the basis of the normal life expectancy of inflammatory bowel disease patients, the early onset of their disease, and the variety of symptoms, inflammatory bowel disease patients were anticipated to be frequent users of outpatients services. This study assesses (1) the characteristics, (2) outpatient health care utilization, and (3) the degree of satisfaction with health care of inflammatory bowel disease patients compared to patients with other gastrointestinal disease. The study method was a secondary analysis of data collected on 395 patients attending the University of Calgary Gastroenterology Outpatient Clinic in 1988. Inflammatory bowel disease patients were significantly younger (P less than 0.001) and better educated (P less than 0.05) than other patients. During the past year inflammatory bowel disease patients consulted significantly more often with their gastroenterologist (P less than 0.001) and spent more time in hospital (P less than 0.05) than other patients. Inflammatory bowel disease patients also consulted more frequently with herbalists and naturopaths. Lastly, inflammatory bowel disease patients were as satisfied with the health care they received as other patients. These results provide information useful for health care planners as well as for those dealing directly with inflammatory bowel disease patients. .A Verhoef MJ; Sutherland LR. .I 274907 .U 91005658 .S Dig Dis Sci 9101; 35(10):1285-90 .M Adult; Chronic Disease; Colonic Diseases, Functional/*CO/DI/PX; Female; Genital Diseases, Female/*CO/DI/PX/SU; Human; Hysterectomy; Pain/*ET; Peritoneoscopy. .T Irritable bowel syndrome in women having diagnostic laparoscopy or hysterectomy. Relation to gynecologic features and outcome. .P JOURNAL ARTICLE. .W We identified irritable bowel syndrome (IBS) in 47.7% of 86 women having diagnostic laparoscopy for chronic pelvic pain, 39.5% of 172 women having elective hysterectomy, and 32.0% of 172 controls age-matched for the hysterectomy group (P = NS). Constipation and pain subtype IBS were more common in hysterectomy patients than controls (P less than 0.05). In laparoscopy patients, dyspareunia was more common in those with IBS than in those without it (P less than 0.05). In the hysterectomy group, more IBS patients had chronic pelvic pain (P less than 0.005), and abnormal menses (P less than 0.01). Chronic pelvic pain was more frequently the only prehysterectomy diagnosis in IBS patients (P less than 0.05), and IBS was present more often when pain was a reason for hysterectomy (P less than 0.01). One year after laparoscopy, IBS patients gave lower overall status ratings (P less than 0.01) and lower pain improvement ratings (P less than 0.05) than non-IBS patients. In women who had a hysterectomy for pain, there was less pain improvement one year later in those with the pain subtype of IBS than in non-IBS patients (P less than 0.05). IBS is associated with gynecologic symptoms and affects the symptomatic outcome of diagnostic laparoscopy and hysterectomy. .A Longstreth GF; Preskill DB; Youkeles L. .I 274908 .U 91005659 .S Dig Dis Sci 9101; 35(10):1291-8 .M Adolescence; Adult; Aged; Anus/PH; Biofeedback (Psychology)/*PH; Fecal Incontinence/*PP/*RH; Female; Follow-Up Studies; Human; Male; Middle Age. .T Investigation of mode of action of biofeedback in treatment of fecal incontinence. .P JOURNAL ARTICLE. .W A study was carried out in 25 incontinent patients to evaluate some of the factors thought to be responsible for the success of retraining for fecal incontinence. Subjects were initially allocated to one of two groups; one group was trained to perceive small rectal volumes (active retraining), the other group carried out the same maneuvers but were not given any information or instruction. Active sensory retraining reduced the sensory threshold from 32 +/- 8 to 7 +/- 2 ml (P less than 0.001), corrected any sensory delay that was present (P less than 0.004), and reduced the frequency of incontinence from 5 +/- 1 to 1 +/- 1 episodes per week (P less than 0.01). Sham retraining caused a modest reduction in the sensory threshold (from 29 +/- 9 to 20 +/- 8; P less than 0.05) but did not significantly reduce the frequency of incontinence. Subsequent strength and coordination training did not significantly improve continence, although at the end of the study, 50% of patients had no incontinent episodes at all and 76% of patients had reduced the frequency of incontinence episodes by more than 75%. This improvement in continence was not associated with any change in sphincter pressures or in the continence to rectally infused saline but was associated with significant improvements in rectal sensation. The functional improvement was sustained over a period of two years in 16 of the 22 patients available for follow-up. In conclusion, the results support the use of retraining in the management of fecal incontinence and suggest that retraining may work by enhancing rectal sensitivity and instilling confidence. .A Miner PB; Donnelly TC; Read NW. .I 274909 .U 91005661 .S Dig Dis Sci 9101; 35(10):1305-7 .M Gastric Mucosa/*ME; Glycoproteins/*ME; Human; Mucus/*ME; Pepsin A/*PH; Sialic Acids/ME. .T Pepsin and the gastric mucus barrier [letter; comment] .P COMMENT; LETTER. .A Sidebotham RL; Batten JJ; Dhir NK; Baron JH. .I 274910 .U 91005662 .S Dig Dis Sci 9101; 35(10):1307-8 .M Adenoma/*PA; Animal; Colon/*PA; Human; Lymphoid Tissue/*PA; Polyposis Syndrome, Familial/*PA. .T Relation between adenomas and colorectal-associated lymphoid tissue in familial polyposis coli [letter] .P LETTER. .A Hillon P; Martin MS; Piard F; Jacquot JF. .I 274911 .U 91005663 .S Diabetes Care 9101; 13(10):1029-33 .M Adult; Blood Glucose/AN; Body Temperature/PH; Diabetes Mellitus, Insulin-Dependent/BL/*DT/PP; Female; Human; Hyperemia/BL/*ET/PP; Hypoglycemia/BL/CI/*CO/PP; Insulin/*TU; Lasers; Male; Regional Blood Flow; Skin/*BS; Support, Non-U.S. Gov't; Sweating; Time Factors; Vasodilation/DE. .T Lack of cutaneous hyperemia in response to insulin-induced hypoglycemia in IDDM. .P JOURNAL ARTICLE. .W Cutaneous blood flow was measured with the laser Doppler technique and by recording cutaneous O2 tension on the forearm and forehead in nine young adult patients with insulin-dependent diabetes mellitus (IDDM) and nine sex- and age-matched healthy control subjects after induction of hypoglycemia. In the healthy subjects, cutaneous blood flow measured with the laser Doppler technique was increased by 120 +/- 26% in the forehead (P less than 0.01) and 196 +/- 50% in the forearm (P less than 0.01) at the glucose nadir (blood glucose 1.8 +/- 0.2 mM) compared with basal blood flow. In contrast, in diabetic patients, cutaneous blood flow was unchanged. The corresponding changes, at the glucose nadir, with cutaneous O2 tension recordings were 286 +/- 131% (P less than 0.05) in control subjects and -22 +/- 15% (NS) in diabetic patients. An impairment of sympathetic nervous function, not detectable by simple cardiovascular tests, could be responsible for the lack of cutaneous hyperemia and sweating and could contribute to unawareness of hypoglycemia in diabetic patients. .A Aman J; Berne C; Ewald U; Tuvemo T. .I 274912 .U 91005664 .S Diabetes Care 9101; 13(10):1034-8 .M Adolescence; Adult; Age Factors; Blood Pressure; Diabetic Retinopathy/BL/CL/*CO/PA; Female; Follow-Up Studies; Hemoglobin A, Glycosylated/AN; Human; Menarche/*; Regression Analysis; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Time Factors. .T Is menarche associated with diabetic retinopathy? .P JOURNAL ARTICLE. .W The goal of this study was to evaluate the association between menarchal status and diabetic retinopathy. Diabetic retinopathy was present in 51 of 129 females; 7 were premenarchal, and 44 were postmenarchal. The range of severity of retinopathy was greater in the postmenarchal group. In multivariate analyses, duration of diabetes, menarchal status, and diastolic blood pressure were associated with the prevalence of diabetic retinopathy. After partitioning the duration of diabetes into years before and years after menarche, both were significant, but the number of years of diabetes after menarche was more strongly associated. At a 4-yr follow-up examination, more postmenarchal than premenarchal females had progression of their retinopathy (P = 0.06). These data suggest that stage of sexual development, as reflected by menarchal status, is associated with the presence and possibly the risk of progression of diabetic retinopathy. .A Klein BE; Moss SE; Klein R. .I 274913 .U 91005665 .S Diabetes Care 9101; 13(10):1039-43 .M Adult; Blood Glucose/*AN; Cholesterol/*BL; Diabetes Mellitus, Insulin-Dependent/BL/*PP; Evaluation Studies; Hemoglobin A, Glycosylated/AN; Human; Lipids/*BL; Male; Muscles/*PP; Physical Endurance/*PH; Risk Factors; Support, Non-U.S. Gov't; Time Factors; Triglycerides/BL; Weight Lifting/*. .T Randomized crossover study of effect of resistance training on glycemic control, muscular strength, and cholesterol in type I diabetic men. .P CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL. .W The goal of this study was to evaluate a program of resistance weight training on cardiovascular risk factors, blood glucose management, and overall strength in diabetic subjects. A randomized crossover design was performed on eight male type I (insulin-dependent) diabetic subjects (mean +/- SD age 31 +/- 3.5 yr, height 176 +/- 5.6 cm, body wt 80 +/- 15 kg, duration of diabetes 12.3 +/- 9.8 yr, and insulin dose 24 U NPH/day and 21 U regular/day). The program consisted of heavy-resistance weight training 3 days/wk for 10 wk, concentrating on the strengthening of major muscle groups through progressive resistance. Blood tests included total cholesterol, triglycerides, very-low-density lipoprotein and high-density lipoprotein cholesterol, and HbA1c. These tests were repeated at three time points during the program. Field-strength testing was performed before and after training. An improvement was seen in the squat (93.6% increase, P less than 0.0001) and bench press (58% increase, P less than 0.005). HbA1c and triglyceride levels showed no change during the resting portion of the experiment but showed a significant change with the training program: HbA1c 6.9 +/- 1.4 vs 5.8 +/- 0.9% (P = 0.05) and triglyceride 5.044 +/- 1.06 vs. 4.628 +/- 0.88 mM (P = 0.01). Self-monitored glucose (taken pre- and postexercise) showed a decrease from 7.85 +/- 3.13 to 7.05 +/- 2.91 mM (P = 0.0001). Very-low-density lipoprotein cholesterol and triglycerides did not change after training. Analysis of variance showed no significant differences over time from the three time points with regard to reductions in cardiovascular risk factors or HbA1c.(ABSTRACT TRUNCATED AT 250 WORDS) .A Durak EP; Jovanovic-Peterson L; Peterson CM. .I 274914 .U 91005666 .S Diabetes Care 9101; 13(10):1044-50 .M Aged; Algorithms; Blood Glucose/*AN; Blood Glucose Self-Monitoring/*MT; Body Weight; Comparative Study; Costs and Cost Analysis; Diabetes Mellitus, Non-Insulin-Dependent/*BL/EC/TH/*UR; Dietary Fiber/AD; Evaluation Studies; Exercise Therapy; Follow-Up Studies; Hemoglobin A, Glycosylated/AN; Human; Male; Middle Age; Patient Compliance; Reagent Strips/DU; Regression Analysis; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.. .T Impact of glucose self-monitoring on non-insulin-treated patients with type II diabetes mellitus. Randomized controlled trial comparing blood and urine testing. .P CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL. .W The goal of this study was to compare the relative efficacy and cost of self-monitoring of blood glucose (SMBG) with routine urine testing in the management of patients with type II (non-insulin-dependent) diabetes mellitus not treated with insulin. Fifty-four patients with type II diabetes mellitus, not treated with insulin, who had inadequate glucose control on diet alone or diet and oral hypoglycemic agents were studied. Patients performed SMBG or urine glucose testing as part of a standardized treatment program that also included diet and exercise counseling. During the 6-mo study, both the urine-testing and SMBG groups showed similar improvement in glycemic control; within each group, there were significant improvements in fasting plasma glucose (reduction of 1.4 +/- 3.2 mM, P less than 0.03) and glycosylated hemoglobin (reduction of 2.0 +/- 3.4%, P less than 0.01) levels. Seventeen (31%) of 54 patients actually normalized their glycosylated hemoglobin values, 9 in the urine-testing group and 8 in the SMBG group. Comparisons between the urine-testing and SMBG groups showed no significant differences in mean fasting plasma glucose (P greater than 0.86), glycosylated hemoglobin (P greater than 0.95), or weight (P greater than 0.19). In patients with type II diabetes mellitus not treated with insulin, SMBG is no more effective, but is 8-12 times more expensive, than urine testing in facilitating improved glycemic control. Our results do not support widespread use of SMBG in diabetic patients not treated with insulin. .A Allen BT; DeLong ER; Feussner JR. .I 274915 .U 91005667 .S Diabetes Care 9101; 13(10):1051-6 .M Adolescence; Adult; Age Factors; Child; Child, Preschool; Comparative Study; Diabetes Mellitus, Insulin-Dependent/*EP; Epidemiologic Methods; Evaluation Studies; Human; Incidence; Infant; Infant, Newborn; Italy/EP; Registries/*ST; Support, Non-U.S. Gov't; Time Factors. .T Incidence of IDDM during 1984-1986 in population aged less than 30 yr. Residents of Turin, Italy. .P JOURNAL ARTICLE. .W The goal of this study was to measure the incidence of insulin-dependent diabetes mellitus (IDDM) during 1984-1986 in residents of Turin, Italy, aged less than 30 yr. The primary data source was the list of all subjects diagnosed with IDDM who attended diabetes clinics in Turin. Other data sources were the general register of death certificates, the list of hospital discharges, and the computerized data base of insulin prescriptions. Eighty incident cases of IDDM were identified during the study in 1,130,284 person-yr for those less than 30 yr of age. Age-adjusted (world standard) incidence rates were 8.05, 8.10, and 6.96/100,000 in the age-groups 0-14, 0-19, and 0-29 yr, respectively. Estimated completeness of the primary data source compared with all other data sources was 91%, whereas the estimated completeness of ascertainment of the registry was 99%. Incidence rates of IDDM in northern Italy compare with those of European countries with low-medium incidence. A population-based register is being established for the province of Turin (951,445 inhabitants aged 0-29 yr) for the collection of incident cases since 1984. .A Bruno G; Merletti F; Pisu E; Pastore G; Marengo C; Pagano G. .I 274916 .U 91005668 .S Diabetes Care 9101; 13(10):1057-61 .M Cold; Comparative Study; Diabetes Mellitus, Non-Insulin-Dependent/CO/*PP; Evaluation Studies; Female; Foot Diseases/ET/*PP; Heat; Human; Male; Middle Age; Predictive Value of Tests; Pressure; Regression Analysis; Sensory Thresholds/PH; Skin Ulcer/ET/*PP; Support, U.S. Gov't, P.H.S.; Toes; Vibration. .T Comparison of quantitative sensory-threshold measures for their association with foot ulceration in diabetic patients. .P JOURNAL ARTICLE. .W We compared the accuracy of cutaneous pressure perception-threshold measurements with that of other sensory-threshold measurements for detecting diabetic foot ulcer patients. Three hundred fourteen non-insulin-dependent diabetic patients were studied, of whom 91 had either a current foot ulcer or a history of foot ulceration. Foot ulcer patients had much higher pressure perception thresholds at the hallux than those without foot ulcers (mean +/- SE 4.63 +/- 0.05 vs. 3.54 +/- 0.04 U, P less than 0.001). The magnitude of association was higher than that for vibration thresholds and markedly greater than those for cool and warm thresholds. Pressure thresholds were highly accurate for identifying foot ulcer patients. At a threshold level of 4.21 U, the sensitivity was 0.84, with a specificity of 0.96. At similar sensitivities for vibration and thermal thresholds, specificities were lower. Foot ulceration and cutaneous pressure perception threshold are strongly associated. Pressure-threshold measurements are extremely accurate and perform at least as well as other quantitative sensory tests in identifying foot ulcer patients. Assessment of the foot pressure threshold may have promise as a simple and inexpensive method for detecting diabetic patients at risk for foot ulcers. .A Sosenko JM; Kato M; Soto R; Bild DE. .I 274917 .U 91005669 .S Diabetes Care 9101; 13(10):1062-8 .M Child; Costs and Cost Analysis; Cross-Cultural Comparison; Developing Countries; Diabetes Mellitus, Insulin-Dependent/DT/EC/*EP/MO/PC; Directories; Human; Incidence; Insulin/SD/TU; International Cooperation/*; Registries/*ST; Research; Risk Factors; Time Factors; World Health/*; World Health Organization/*. .T WHO Multinational Project for Childhood Diabetes. WHO Diamond Project Group. .P JOURNAL ARTICLE. .W Insulin-dependent diabetes mellitus (IDDM) is one of the most important chronic diseases of children worldwide. IDDM leads to an 8- to 10-fold excess risk of mortality in developed countries, whereas in developing countries, most cases die within a few years. A 60-fold international gradient in IDDM incidence has been reported, and epidemic periods have been identified. A new World Health Organization program, Multinational Project for Childhood Diabetes (Diabetes Mondiale or DIAMOND), has been developed to investigate and characterize global incidence, mortality, and health care. Over 10 yr (1990-1999), this study will collect population-based data concerning IDDM in greater than 90 centers in 50 countries worldwide. The goals of DIAMOND are to collect standard information on incidence, risk factors, and mortality associated with IDDM; evaluate the efficiency and effectiveness of health care and the economics of diabetes; and establish national and international training programs in diabetes epidemiology. It is hoped that the DIAMOND project will be instrumental for the prevention of this serious disease and its sequelae. .I 274918 .U 91005670 .S Diabetes Care 9101; 13(10):1069-73 .M Adolescence; Adult; Aged; Aged, 80 and over; Albuminuria/*DI/UR; Centrifugation; Comparative Study; Enzyme-Linked Immunosorbent Assay/IS/ST; Evaluation Studies; Female; Human; Male; Middle Age; Observer Variation; Radioimmunoassay/MT/ST; Reagent Strips/*DU/ST; Sampling Studies; Time Factors. .T Evaluation of new rapid office test for microalbuminuria and its comparison to fully quantitative radioimmunoassay. .P JOURNAL ARTICLE. .W A novel enzyme-linked immunosorbent assay (ELISA [Dialbumin]) for rapid office measurement of microalbuminuria was evaluated and its performance compared with that of a commercially available radioimmunoassay (double-antibody albumin). Urine samples containing between 0.75 and 1800 micrograms/ml of albumin were obtained from 31 diabetic patients and assayed by both methods. A comparison of the paired values obtained from the two methods gave a correlation coefficient of greater than 0.99. The Dialbumin assay, which used detachable eight-well strips (1 strip/sample), 10-min incubation, tap water wash, and a 2-min color development step, was read on both an ELISA reader and a hand-held analytical device (Acc-U-Dial) designed specifically for this test. The findings of this study indicate that the Dialbumin assay, used in conjunction with the Acc-U-Dial device, affords a rapid, convenient, and sensitive method for quantitative determination of a broad range (0.3-1280 micrograms/ml) of urinary albumin levels in the office setting. .A Neuman RG; Bonomini LV; Braunstein SN. .I 274919 .U 91005671 .S Diabetes Care 9101; 13(10):1074-7 .M Clonidine/*TU; Comparative Study; Diabetes Mellitus, Non-Insulin-Dependent/*DT; Diabetic Neuropathies/*DT; Double-Blind Method; Drug Evaluation; Human; Male; Middle Age; Pain Measurement/*DE; Pentoxifylline/*TU; Time Factors. .T Lack of effect of clonidine and pentoxifylline in short-term therapy of diabetic peripheral neuropathy. .P CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL. .W The goal of this study was to confirm or rule out anecdotal reports of beneficial effects of clonidine and pentoxifylline in the treatment of painful diabetic peripheral neuropathy. Clonidine was administered to 16 subjects at two dosage levels (0.1 and 0.2 mg/day) and was compared to placebo in a crossover design, with each phase lasting 4 wk. Either pentoxifylline (400 mg 3 times/day) or placebo was given to 21 subjects in a 12-wk trial. Discomfort was characterized and rated with a subjective pain score (range 0-20). There was a significant decrease in pain score from baseline with both active drugs (P less than 0.05), but this was no better than the response to placebo (P less than 0.30 for clonidine and P less than 0.95 for pentoxifylline). This study does not demonstrate a short-term benefit of either clonidine or pentoxifylline in the treatment of peripheral neuropathy. .A Cohen KL; Lucibello FE; Chomiak M. .I 274920 .U 91005672 .S Diabetes Care 9101; 13(10):1077-80 .M Adolescence; Adult; Age Factors; Aged; Comparative Study; Diabetes Mellitus, Insulin-Dependent/*PP; Diabetes Mellitus, Non-Insulin-Dependent/*PP; Diabetic Neuropathies/CO/*PP; Evaluation Studies; Foot Diseases/*ET; Human; Malleus; Middle Age; Neural Conduction/PH; Neurologic Examination/*IS; Regression Analysis; Sensory Thresholds/PH; Skin Ulcer/*ET; Thumb; Time Factors; Toes; Vibration/*. .T Measuring vibration sensations with graduated tuning fork. Simple and reliable means to detect diabetic patients at risk of neuropathic foot ulceration. .P CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL. .W To find a simple and reliable means to measure vibration sensations, 189 diabetic patients and 88 control subjects were tested at different sites with a graduated tuning fork. Within-test variation at big toes reached 8.4% in diabetic patients vs. 2.2% in control subjects. Mean contralateral variation was 7.5% in diabetic patients vs. 2.5% in control subjects. Tuning-fork sensations were inversely correlated with duration of diabetes, whereas no correlation was found with HBA1c levels or the severity of retinopathy. Ninety-nine (52%) patients had vibratory sensation at big toes of less than 99th percentile of normal values for age. In addition, 51% of the patients with clinical symptoms at extremities (n = 67), 70% of the patients without tendon reflexes (n = 50), and 75% of the patients with abnormal nerve conduction velocities (n = 60) also had low vibration sensations. All patients with lower-limb injuries (n = 7) had values at big toes of less than 2. Altogether, the graduated tuning fork represents a simple and reliable alternative to quantitate vibration sensations. Long-term follow-up of asymptomatic patients will indicate whether these abnormalities reflect underlying neuropathy. Patients with abnormal values at screening will necessitate additional investigations and special foot-care education programs. .A Thivolet C; el Farkh J; Petiot A; Simonet C; Tourniaire J. .I 274921 .U 91005673 .S Diabetes Care 9101; 13(10):1080-4 .M Algorithms/*; Blood Glucose Self-Monitoring/*; Child; Comparative Study; Diabetes Mellitus, Insulin-Dependent/*DT; Drug Therapy, Computer-Assisted/*IS; Evaluation Studies; Female; Human; Hypoglycemia/CI; Insulin/*AD/AE; Male; Microcomputers; Prospective Studies; Support, Non-U.S. Gov't. .T Controlled study in diabetic children comparing insulin-dosage adjustment by manual and computer algorithms. .P CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL. .W A controlled trial of a new microprocessor device for insulin-dosage adjustment was undertaken in two matched groups of a priori well-controlled diabetic children. A prospective study design with three equal 8-wk periods was used. In the first period, both groups used manual methods for insulin-dosage adjustment after manual criteria. In the second period, one group of children adjusted insulin dosage by computer algorithms, whereas the other continued to use manual methods. In the third period, both groups again adjusted insulin by traditional methods. Mean premeal glycemia and glycosylated hemoglobin levels did not change in either group throughout the study. During the second period, episodes of hypoglycemia were more frequent in children without the computer than in those who used the device. In keeping with the latter outcome, the group that used the microprocessor device was given less insulin in the second period than the first (0.88 +/- 0.02 vs. 0.94 +/- 0.02 U.kg-1.day-1, P less than 0.0001) and in comparison to the control group of patients who concurrently were given an increased insulin dose in the second period compared with the first. This study showed that insulin treatment through specific computer-mediated dosage-adjusting algorithms was safe and minimized hypoglycemia by effectively accommodating seasonally changing insulin requirements. We recommend the device to help diabetic children and their families in the care of insulin-dependent diabetes. .A Chiarelli F; Tumini S; Morgese G; Albisser AM. .I 274922 .U 91005674 .S Diabetes Care 9101; 13(10):1084-8 .M Adolescence; Adrenal Medulla/IM; Adult; Aged; Autoantibodies/*AN; Carrier Proteins/*IM; Child; Child, Preschool; Complement/*IM; Cross-Sectional Studies; Diabetes Mellitus, Insulin-Dependent/EP/*IM/PP; Electrocardiography; Female; Fluorescent Antibody Technique; Ganglia, Sympathetic/*IM; Heart Rate; Human; Infant; Male; Middle Age; Stains and Staining; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Vagus Nerve/*IM/PP. .T Complement-fixing antibodies to sympathetic and parasympathetic tissues in IDDM. Autonomic brake index and heart-rate variation. .P JOURNAL ARTICLE. .W We describe herein complement-fixing anti-adrenal medullary (CF-ADM) and anti-sympathetic ganglia (CF-SG) antibodies in insulin-dependent diabetes mellitus (IDDM). This study describes complement-fixing anti-vagus (CF-V) nerve antibodies and their relationship to the cardiovascular autonomic brake index (a measure of transient decrease in heart rate during the 1st min after a tilt), and R-R interval variation with deep breathing. CF-V was detectable in 7 of 83 (8.4%) subjects with IDDM aged 1.5-65.5 yr (mean +/- SE 28.7 +/- 1.8 yr) and duration of diabetes 0-47 yr (11.8 +/- 1.4 yr). Seventy-six nondiabetic subjects (aged 10-65 yr) all had negative CF-V scores. CF-V scores correlated with CF-ADM (0-16 yr of IDDM, r = 0.61, P less than 0.0001) and CF-SG (r = 0.39, P less than 0.05). Seventy IDDM subjects (aged 28 +/- 5 yr, duration of diabetes 17 +/- 3 yr) without proteinuria or proliferative retinopathy were screened for CF-ADM, CF-SG, and CF-V antibodies. Five of 70 (7.1%) had CF-SG only (negative for CF-ADM and CF-V). Brake indices ranged from 14.7 to 51.3 (37.3 +/- 6.9). Three of 70 (4.2%) had CF-ADM only, with brake indices from 26.9 to 45.1 (32.9 +/- 6.1). Four of 70 (5.7%) had CF-V antibodies only, with brake indices of 12.7-17.3 (15.1 +/- 1.1). Subjects with CF-SG or CF-ADM (anti-sympathetic) had higher brake indices than subjects with CF-V (anti-parasympathetic) antibodies (P less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) .A Rabinowe SL; Brown FM; Watts M; Smith AM. .I 274923 .U 91005675 .S Diabetes Care 9101; 13(10):1089-91 .M Adolescence; Age Factors; Blood Glucose/*AN; Blood Glucose Self-Monitoring/*; Child; Diabetes Mellitus/*BL; Diabetic Angiopathies/BL/ET; Diabetic Neuropathies/BL/ET; Female; Human; Hypoglycemia/BL/ET/PC; Puberty/PH; Time Factors. .T Too uptight about tight control? .P JOURNAL ARTICLE. .A Copeland KC. .I 274924 .U 91005676 .S Diabetes Care 9101; 13(10):1092 .M Blood Glucose/*AN; Fraud/*; Human; Reagent Strips/*ST. .T Cheating with glucose test strips [letter; comment] .P COMMENT; LETTER. .A Horwitz DL. .I 274925 .U 91005677 .S Diabetes Care 9101; 13(10):1092-3 .M Adult; Aged; Amputation; Child; Diabetes Mellitus, Insulin-Dependent/*CO; Foot Deformities, Acquired/*ET; Human; Leg/SU. .T Acquired foot deformity in diabetic children [letter] .P LETTER. .A Eichold S. .I 274926 .U 91005678 .S Diabetes Care 9101; 13(10):1093-4 .M Animal; Case Report; Cattle; Desensitization, Immunologic; Diabetes Mellitus/*CO/IM; Drug Hypersensitivity/*ET; Human; Insulin, Lente/*AE/CL; Male; Middle Age; Swine. .T Pancreatic diabetes with severe generalized allergy to purified beef, pork, and human insulins [letter] .P LETTER. .A Yoshino G; Yamochi W; Moriyama H; Ueno H; Inui A; Oimomi M; Baba S. .I 274927 .U 91005680 .S Diabetes Care 9101; 13(10):1095-6 .M Blood Glucose/*AN; Computers; Eating/*PH; Female; Human; Male; Reference Standards; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Time Factors. .T Quantitation of the glucose area response to a meal [letter; comment] .P COMMENT; LETTER. .A Gannon MC; Nuttall FQ. .I 274928 .U 91005681 .S Diabetes Care 9101; 13(10):1096-7 .M Body Mass Index; Diabetes Mellitus, Non-Insulin-Dependent/*BL; Female; Human; Male; Sex Characteristics/*. .T Sex differences in metabolic control [letter] .P LETTER. .A Canivet C. .I 274929 .U 91005682 .S Diabetes Care 9101; 13(10):1097-8 .M Adolescence; Child; Diabetes Mellitus, Insulin-Dependent/*CO; Human; Hypoglycemia/EP/*TH; School Health Services/*OG; Support, Non-U.S. Gov't; Virginia/EP. .T Hypoglycemia. Can the school respond? [letter] .P LETTER. .A Clarke WL; Snyder AL. .I 274930 .U 91005683 .S Diabetes Care 9101; 13(8):821-9 .M Blood Glucose/AN; Cardiovascular Diseases/BL/ET/PC; Cholesterol/BL; Diabetes Mellitus, Non-Insulin-Dependent/*BL/CO; Diabetic Angiopathies/BL/ET/PC; Diabetic Diet; Fatty Acids, Omega-3/AD/PD; Female; Fish Oils/AD/*PD; Food, Fortified; Hemostasis/DE; Human; Lipids/BL; Male; Support, Non-U.S. Gov't; Thromboxane B2/BL; Triglycerides/BL. .T Effects of fish oil supplements in NIDDM subjects. Controlled study. .P CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL. .W The aim of this study was to evaluate the effects of a fish oil preparation (MaxEPA) on hemostatic function and fasting lipid and glucose levels in non-insulin-dependent diabetic (NIDDM) subjects. Eighty NIDDM outpatients aged 55.9 yr (mean SD 11.5 yr) participated in a prospective double-blind placebo-controlled study of MaxEPA capsules (10 g/day) or olive oil (control) treatment over 6 wk. Patients received either MaxEPA or olive oil in addition to preexisting therapy. Metabolic and hemostatic variables were measured before treatment and after 3 and 6 wk. Platelet membrane eicosapentaenoic acid (EPA) content increased in the treatment group (P less than 0.001). MaxEPA supplementation was associated with a significant fall in total triglycerides (P less than 0.001) but did not affect total cholesterol (P = 0.7) compared with control treatment. Fasting plasma glucose increased after 3 wk (P = 0.01) but not after 6 wk (P = 0.17) treatment with MaxEPA. Spontaneous platelet aggregation in whole blood fell in the MaxEPA group (P less than 0.02) after 6 wk, but there were no changes in agonist-induced platelet aggregation, thromboxane generation in platelet-rich plasma, or plasma beta-thromboglobulin and platelet factor IV levels. An increase in clotting factor VII (P = 0.02), without changes in fibrinogen or factor X levels, occurred in the MaxEPA group. Similar reductions in blood pressure were observed in both groups. Dietary supplementation with MaxEPA capsules (10 g/day) in NIDDM subjects is associated with improvement in hypertriglyceridemia but with deleterious effects in factor VII and blood glucose levels. Most indices of platelet function are unaffected by this therapy. .A Hendra TJ; Britton ME; Roper DR; Wagaine-Twabwe D; Jeremy JY; Dandona P; Haines AP; Yudkin JS. .I 274931 .U 91005684 .S Diabetes Care 9101; 13(8):830-5 .M Adolescence; Adult; Australia/EP; Blood Glucose/AN; Cholesterol/BL; Diabetes Mellitus/BL/*EP; Female; Glucose Tolerance Test; Human; Hyperinsulinism/BL/*EP; Hyperlipidemia/BL/*EP; Male; Middle Age; Prevalence; Support, Non-U.S. Gov't; Triglycerides/BL. .T Diabetes, hyperinsulinemia, and hyperlipidemia in small aboriginal community in northern Australia. .P JOURNAL ARTICLE. .W A small rural Aboriginal community in northern Australia was surveyed for diabetes, impaired glucose tolerance (IGT), hyperinsulinemia, and lipid levels. Of the 122 adults greater than 17 yr of age who participated (95% response rate), 11.5% had diabetes, 7.4% had IGT, and the remaining 81.1% had normal glucose tolerance. Both diabetes and IGT were strongly age related. This high frequency of diabetes occurred, despite the population being relatively lean. Although the body mass index (BMI) increased with age in both men and women, only 25% of the population overall had BMI greater than 25 kg/m2. There were wide ranges of insulin responses to glucose, with the upper tertile of 2-h insulin levels being more than seven times higher than the lower tertile (144 +/- 13 vs. 19 +/- 1 mU/L). Hyperinsulinemia was associated with IGT, elevated triglycerides, and lower high-density lipoprotein cholesterol levels. Lipid abnormalities were much more frequent among men than women. Cholesterol levels were an average of 0.55 mM higher and triglycerides an average of 1.05 mM higher in men than in women, and both increased with age. In conclusion, this small isolated Aboriginal population from northern Australia had an unexpectedly high frequency of diabetes (in view of their relative leanness) in association with a high frequency of metabolic abnormalities indicative of insulin resistance (hyperinsulinemia, IGT, hypertriglyceridemia). .A O'Dea K; Lion RJ; Lee A; Traianedes K; Hopper JL; Rae C. .I 274932 .U 91005685 .S Diabetes Care 9101; 13(8):836-40 .M Adolescence; Adult; Age Factors; Diabetes Mellitus, Non-Insulin-Dependent/CO/*EP/GE; Female; Human; Incidence; Indians, North American/GE; Male; Middle Age; Periodontal Diseases/*EP/ET; Prevalence; Sex Factors; Support, U.S. Gov't, P.H.S.. .T Periodontal disease and NIDDM in Pima Indians. .P JOURNAL ARTICLE. .W The goal of this study was to determine the prevalence and incidence of periodontal disease and its relationship with non-insulin-dependent diabetes mellitus (NIDDM). Two thousand two hundred seventy-three Pima Indians (949 men, 1324 women) aged greater than or equal to 15 yr from the Gila River Indian Community in Arizona were examined between 1983 and 1989. Periodontal disease was diagnosed by tooth loss and by percentage of interproximal crestal alveolar bone loss ascertained from panoramic radiography. Subjects with little or no evidence of periodontal disease were classified as nondiseased. Thus, the incidence of advanced periodontal disease was determined. The age- and sex-adjusted prevalence of periodontal disease at first dental examination was 60% in subjects with NIDDM and 36% in those without. Twenty-two new cases developed in a subset of 701 subjects (272 men, 429 women) aged 15-54 yr who initially had little or no evidence of periodontal disease and had at least one additional dental examination. The incidence of periodontal disease in this group was similar in men and women (incidence-rate ratio 1.0, 95% confidence interval [Cl] 0.5-1.9, controlled for age and diabetes). Higher age predicted a greater incidence of periodontal disease (chi 2 = 30.6, df = 3, P less than 0.001, controlled for sex and diabetes). The rate of periodontal disease in subjects with diabetes was 2.6 times (95% Cl 1.0-6.6, controlled for age and sex) that observed in those without. Although periodontal disease was common in nondiabetic Pima Indians, in whom most of the incident cases occurred, diabetes clearly conferred a substantially increased risk. Thus, periodontal disease should be considered a nonspecific complication of NIDDM. .A Nelson RG; Shlossman M; Budding LM; Pettitt DJ; Saad MF; Genco RJ; Knowler WC. .I 274933 .U 91005686 .S Diabetes Care 9101; 13(8):841-7 .M Aged; Carbohydrates/ME; Comparative Study; Diabetes Mellitus, Non-Insulin-Dependent/*DH/ME; Diabetic Diet/*; Female; Glucose/ME; Human; Lipids/ME; Male; Middle Age; Patient Education/*MT; Support, Non-U.S. Gov't. .T Impact of intensive educational approach to dietary change in NIDDM. .P JOURNAL ARTICLE. .W The aim of this study was to compare the effects of an intensive educational approach incorporating longer time, greater simplicity, repetition, and cognitive motivational techniques with a conventional one in subjects with established non-insulin-dependent diabetes mellitus (NIDDM) whose weight, glycemic control, and diet were not optimal. Subjects were randomly allocated to intensive or conventional education. Of 350 subjects, 70 met the study criteria, which included established NIDDM (greater than or equal to 3 mo), suboptimal recent glycemic control, dietary fat intake greater than or equal to 35% of total energy intake, and body mass index greater than or equal to 25 kg/m2. The intensive approach was associated with significantly greater improvements in dietary compliance, dietary intake (complex carbohydrate, [P = 0.013], legumes [P less than 0.0001], fiber [P less than 0.0001], total fat [P less than 0.004], saturated fat [P less than 0.004]), and total cholesterol level (P = 0.007). The transient improvement in glycemic control was similar in both groups. An intensive education program can improve dietary compliance in established NIDDM subjects more than a conventional one. These recommended dietary improvements achieve better improvement in total cholesterol but do not necessarily improve glycemic control. .A Campbell LV; Barth R; Gosper JK; Jupp JJ; Simons LA; Chisholm DJ. .I 274934 .U 91005687 .S Diabetes Care 9101; 13(8):848-54 .M Adult; Aged; Blood Glucose/*ME; Diabetes Mellitus, Non-Insulin-Dependent/BL/*EP; Female; Glucose Tolerance Test; Health Surveys; Human; Middle Age; Pregnancy; Pregnancy in Diabetes/*ME/PP; Prevalence; Regression Analysis; Support, U.S. Gov't, P.H.S.; United States/EP. .T Effects of childbearing on glucose tolerance and NIDDM prevalence [published erratum appears in Diabetes Care 1990 Nov;13(11):1138] .P JOURNAL ARTICLE. .W The goal of this study was to estimate the effects of childbearing on subsequent glucose tolerance and non-insulin-dependent diabetes mellitus (NIDDM) prevalence. A sample of subjects from 64 different locations in the United States were recruited for inclusion in the Second National Health and Nutrition Examination Survey. A complex survey design was used to select a probability sample of subjects from each location. A total of 4577 women were recruited, of whom 3057 underwent clinical and laboratory evaluation for the presence of diabetes mellitus. Women were classified as to their glucose tolerance based on the results of an oral glucose tolerance test or previous physician diagnosis of diabetes mellitus combined with current use of hypoglycemic medication. Childbearing was defined as number of live births experienced by each woman at the time of the interview. Fasting plasma glucose increased linearly with increasing number of live births (coefficient 0.009, 95% confidence interval [CI] 0.006-0.012), as did the 2-h value (coefficient 0.015, 95% CI 0.009-0.021). Adjustment for age, body mass index (BMI), education, and income substantially reduced the magnitude of the association between childbearing and either plasma glucose measurement. When the prevalence of NIDDM in relation to childbearing was examined with logistic regression analysis, a significant linear increase in diabetes prevalence was seen with increasing number of live births (relative prevalence of NIDDM, 1 birth vs. 0 = 1.73, 95% CI 1.39-2.15), but adjustment for age, BMI, education, and income greatly reduced the magnitude of this association (relative prevalence of NIDDM, 1 birth vs. 0 = 1.07, 95% CI 0.98-1.17).(ABSTRACT TRUNCATED AT 250 WORDS) .A Boyko EJ; Alderman BW; Keane EM; Baron AE. .I 274935 .U 91005688 .S Diabetes Care 9101; 13(8):855-63 .M Bezafibrate/PD/*TU; Blood Glucose/*AN; Diabetes Mellitus, Non-Insulin-Dependent/BL/*DT; Dose-Response Relationship, Drug; Fatty Acids, Nonesterified/BL; Female; Glucose Tolerance Test; Human; Male; Middle Age; Support, Non-U.S. Gov't; Triglycerides/BL. .T Lowering of plasma glucose concentrations with bezafibrate in patients with moderately controlled NIDDM. .P JOURNAL ARTICLE. .W The goal of this study was to investigate whether treatment with bezafibrate improves glucose tolerance in non-insulin-dependent diabetes mellitus (NIDDM). The study included 37 NIDDM patients with HbA1 concentrations greater than 8.5% and normal kidney and liver function who were being treated with diet alone or diet together with a sulfonylurea drug. One patient withdrew because of constipation. At randomization and after 3 mo of treatment, patients were given a standard mixed-test-meal tolerance test (MTT; 500 cal) after an overnight fast, and plasma glucose, insulin, C-peptide, metabolite, nonesterified fatty acid (NEFA), and triglyceride concentrations were measured at 15- to 30-min intervals. Serum lipid, HbA1, and fructosamine concentrations were measured at monthly intervals. Glucose, NEFA, and triglyceride concentrations were significantly lower throughout the second MTT in bezafibrate patients (P less than 0.01-0.001) but not in the placebo group. Fasting serum insulin and C-peptide levels, but not postprandial concentrations, were reduced only in bezafibrate patients (P less than 0.05). After 3 mo, mean fasting serum triglyceride concentrations fell from 2.2 to 1.4 mM (P less than 0.001), total serum cholesterol concentrations from 6.3 to 5.5 mM (P less than 0.001), and low-density lipoprotein cholesterol concentrations from 4.2 to 3.5 mM (P less than 0.001) in bezafibrate patients. There were no changes in serum lipid concentrations in the placebo group. Treatment of patients with moderately controlled NIDDM with bezafibrate improves glucose tolerance and the serum lipid profile. Bezafibrate treatment may be a useful adjunct to hypoglycemic therapy in patients with NIDDM. .A Jones IR; Swai A; Taylor R; Miller M; Laker MF; Alberti KG. .I 274936 .U 91005689 .S Diabetes Care 9101; 13(8):864-71 .M Adolescence; Adult; Aged; Albuminuria/ME/*PP; Circadian Rhythm/*PH; Comparative Study; Creatinine/UR; Female; Human; Male; Middle Age; Specimen Handling; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.. .T Comparison of albumin excretion rate obtained with different times of collection. .P JOURNAL ARTICLE. .W This study was undertaken to assess the usefulness of different techniques for determination of albumin excretion rate (AER). Ninety patients with type I (insulin-dependent) diabetes mellitus and 45 with type II (non-insulin-dependent) diabetes mellitus, with AER/24 h of less than 200 micrograms/min, were included. All patients were free of major systemic complications of diabetes and overt kidney disease (mean serum creatinine 1.1 +/- 0.1 mg/dl, range 0.4-1.2 mg/dl). We compared timed day, night, and 24-h specimens, as well as timed spot specimens during water-induced diuresis. Most patients with type I (75 of 90) and type II (30 of 45) diabetes had AER less than 20 micrograms/min and showed significant differences in AER that were dependent on the collection time. Differences were diminished or absent with AER less than 20 micrograms/min. Sensitivity, specificity, and prediction rates of AER in different specimens were evaluated against 24-h AER. Use of albumin concentrations and albumin-creatinine ratios did not improve test performance in comparison with AER. Sampling time and the overall rate of AER influenced measurement of urinary albumin excretion. Day or 24-h AER is most useful to determine the presence of abnormal AER. AER and albumin concentration in spot samples are of limited use for initial screening and frequently require day or 24-h specimens of AER for confirmation. Day or 24-h AER should be used for long-term follow-up of the diabetic patient. .A Wiegmann TB; Chonko AM; Barnard MJ; MacDougall ML; Folscroft J; Stephenson J; Kyner JL; Moore WV. .I 274937 .U 91005690 .S Diabetes Care 9101; 13(8):872-5 .M Adolescence; Adult; Blood Glucose Self-Monitoring/MT; Blood Proteins/*AN; Diabetes Mellitus/BL; Female; Glycosylation; Hexosamines/*BL/DU; Human; Pregnancy; Pregnancy in Diabetes/*BL. .T Total serum glycosylated proteins in detection and monitoring of gestational diabetes. .P JOURNAL ARTICLE. .W The goal of this study was to determine whether serum glycosylated protein levels (i.e., fructosamine) can reliably screen for gestational diabetes and whether these levels are valid markers of short-term glycemic control in the third trimester of pregnancy. Ninety-seven pregnant women at 26-28 wk gestation were evaluated over 9 mo. HbA1c and serum glycosylated protein (serum fructosamine) were determined at the baseline venipuncture of the 100-g oral glucose tolerance test performed to detect gestational diabetes. Of the 97 women studied, 13 tested positive for gestational diabetes (National Diabetes Data Group criteria). There were significant differences in the fasting and 1-, 2-, and 3-h glucose values between nondiabetic and diabetic patients (P less than 0.005 at each time point). No difference was noted in the baseline serum glycosylated protein level (2.02 +/- 0.08 vs. 1.98 +/- 0.02 mM, NS) or HbA1c level (4.42 +/- 0.2 vs. 4.6 +/- 0.3%, NS) between gestational and nondiabetic patients. Diabetic patients were followed at 2-wk intervals, with serum glycosylated protein analysis, HbA1c, fasting glucose, and mean glucose determined by outpatient monitoring. Serum glycosylated protein correlated significantly to fasting blood glucose (r = 0.81, P less than 0.001) and mean outpatient glucose (r = 0.62, P less than 0.001) at the 2-wk follow-up visits. No correlation was found between HbA1c and fasting blood glucose (r = 0.11, NS) or mean outpatient glucose (r = -0.12, NS) during the follow-up period. The serum glycosylated protein level (serum fructosamine) is not a useful screening test for gestational diabetes. However, this assay shows potential as an objective marker of short-term control in evaluating the maternal glycemic state. .A Cefalu WT; Prather KL; Chester DL; Wheeler CJ; Biswas M; Pernoll ML. .I 274938 .U 91005691 .S Diabetes Care 9101; 13(8):876-82 .M Diabetes Mellitus/*EP/MO/PC; Human; Influenza/*EP/MO/PC; Influenza Vaccine/TU; Prognosis; Risk Factors; Time Factors; Vaccination. .T Influenza infection and diabetes mellitus. Case for annual vaccination. .P CLINICAL TRIAL; JOURNAL ARTICLE; REVIEW; REVIEW, MULTICASE. .W Herein, epidemiological data on influenza pneumonia and mortality, results of clinical studies, and the outcome of influenza vaccination trials are reviewed. All excess mortality studies that specify for underlying disease list diabetes as one of the major risk factors. During influenza epidemics, death rates among patients with diabetes mellitus may increase by 5-15%. Diabetes mellitus is also mentioned as a risk factor in most clinical studies, making up 3-14% of the patients studied. Even in recent studies, diabetes mellitus is only preceded as a risk factor by cardiovascular disease and chronic pulmonary disorders. To what extent cardiovascular disease and old age contribute to the increased influenza mortality and morbidity in diabetic patients remains unclear. The influence of epidemic influenza on the incidence of diabetic acidosis in combination with an impaired immune response to both Staphylococcus aureus and the influenza virus suggests that diabetes mellitus itself is the main risk factor. It is concluded that all patients with diabetes mellitus should receive annual vaccinations and that, in official recommendations, patients with diabetes mellitus should be mentioned as a separate risk group. Whole-virus vaccines are preferred over subunit vaccines. .A Diepersloot RJ; Bouter KP; Hoekstra JB. .I 274939 .U 91005692 .S Diabetes Care 9101; 13(8):883-5 .M Adult; Autoantibodies/BL; Case Report; Diabetes Mellitus, Insulin-Dependent/BL/*ET; Human; Kidney Transplantation/*AE/CT; Male; Mass Screening/MT; Sibling Relations/*; Support, U.S. Gov't, P.H.S.; Tissue Donors/*. .T Development of IDDM after donating kidney to diabetic sibling. .P JOURNAL ARTICLE. .W The goal of this study was to describe a patient who developed insulin-dependent diabetes mellitus (IDDM) after donating a kidney to his sibling and to suggest a possible solution to prevent such an occurrence. A 42-yr-old man was found to have islet cell autoantibodies (ICAs) as part of a screening program of first-degree relatives with IDDM. Two years previously, he had donated his kidney to his HLA-identical sibling with long-standing IDDM. Both oral and intravenous glucose tolerance tests demonstrated a gradual loss of insulin secretion and increasing glucose intolerance until the patient developed IDDM 6 yr after the nephrectomy. Whether the presence of ICA is an absolute contraindication to being a kidney donor could be debated. Nonetheless, ICA should be used as a screening test to identify individuals at risk for subsequent IDDM. For those found to be positive, counseling should be provided. .A Riley WJ; Maclaren NK; Spillar RP. .I 274940 .U 91005693 .S Diabetes Care 9101; 13(8):886-8 .M Blood Glucose Self-Monitoring/*MT; Comparative Study; Hemoglobin A, Glycosylated/*AN; Human; Reagent Strips; Support, U.S. Gov't, P.H.S.. .T Mail-in paper strip vs. microcolumn technique for measurement of glycosylated hemoglobin. .P JOURNAL ARTICLE. .W We compared glycosylated hemoglobin (GHb) determined from capillary blood samples on paper strips with a standard microcolumn technique in a cross-sectional observational study with laboratories blinded to duplicate samples. Both the standard and the filter strip laboratories were provided with 80 uniquely identified blood samples from 40 individuals. Each laboratory ran duplicate analyses on each sample, yielding 160 GHb values. The within-laboratory correlations between blinded duplicates were 0.98 for the standard (microcolumn technique) and 0.94 for the filter paper (affinity technique) laboratories. The between-laboratory correlations ranged from 0.69 to 0.77. When classifying patients by quartile of glycemic control, the laboratories agreed on 60% of the patients. In an effort to identify sources of between-laboratory variability, varying quantities of blood were applied to strips and reanalyzed. Five microliter drops always yielded inflated estimates of GHb. These data suggest that the estimates of GHb obtained from mail-in paper strips, although internally consistent, differ in important ways from standard laboratory values, reemphasizing the need for caution in the interpretation of interlaboratory and intermethod comparisons. .A Slemenda CW; Marrero DG; Fineberg SE; Moore PS; Gibson R. .I 274941 .U 91005694 .S Diabetes Care 9101; 13(8):888-92 .M Adult; Blood Glucose/AN; C-Peptide/BL; Cacao/*; Carbohydrates/ME; Comparative Study; Diabetes Mellitus, Insulin-Dependent/BL/*ME/UR; Diabetic Diet/*; Female; Glycosuria/ME; Human; Male; Potatoes/*; Sucrose/ME. .T Effect of isocaloric substitution of chocolate cake for potato in type I diabetic patients. .P JOURNAL ARTICLE. .W Traditional dietary advice given to people with diabetes includes eliminating simple sugars (primarily sucrose) from the diet. Many people have difficulty following this recommendation. Because patients with type I (insulin-dependent) diabetes do not need overall calorie restriction, there is no caloric reason to restrict sucrose. In this study, we looked at the effect of the isocaloric substitution of a piece of chocolate cake for a baked potato in a mixed meal to determine whether this would increase the blood glucose in patients with type I diabetes. The glucose response to a cake-added meal was significantly greater than to a standard meal. The glucose response was no different between a cake-substitution meal and a standard meal. The reproducibility studies showed no difference between repeated standard meals. The urinary glucose excretion was significantly greater after a cake-added meal but was no different with the other pairs. There were no significant differences in the counterregulatory hormone responses at baseline between any of the paired studies. In conclusion, patients with type I diabetes may substitute a sucrose-containing dessert for another carbohydrate in their diet without compromising their postprandial glucose response. These data suggest that a dessert exchange may be helpful and not harmful in the management of diabetic patients. There is an inherent variability (at least 16%) in an insulin-requiring patient's response to a meal, making self-monitoring of blood glucose and adjustment of insulin doses necessary to achieve near euglycemia. .A Peters AL; Davidson MB; Eisenberg K. .I 274942 .U 91005695 .S Diabetes Care 9101; 13(8):893-5 .M Adult; Diabetes Mellitus, Insulin-Dependent/*CO/PP/PX; Diabetes Mellitus, Non-Insulin-Dependent/*CO/PP/PX; Diabetic Neuropathies/CO/PP/PX; Human; Impotence/EP/*ET/PX; Incidence; Male; Mental Disorders/EP/*ET; Middle Age; Regression Analysis; Support, U.S. Gov't, P.H.S.. .T Relationship of psychiatric illness to impotence in men with diabetes. .P JOURNAL ARTICLE. .W Clinical data from 37 adult males with diabetes mellitus (insulin dependent, n = 22; non-insulin dependent, n = 15) who had undergone psychiatric diagnosis and peripheral nerve conduction studies were reviewed to determine whether psychiatric illness was significantly related to complaints of sexual dysfunction. Main-effects testing revealed that impotence was associated with both neuropathy (P less than 0.01) and psychiatric illness (P less than 0.001). Logistic regression analysis was then used to determine the independent relationships of these two variables with impotence. After controlling for the effects of neuropathy, psychiatric illness (generalized anxiety disorder and depression) remained significantly associated with sexual dysfunction (P less than 0.01). These data allow for the hypothesis that psychiatric illness may be an important contributor to impotence in diabetic men, as it is in nondiabetic men, even when neuropathic complications of the disease are present. .A Lustman PJ; Clouse RE. .I 274943 .U 91005696 .S Diabetes Care 9101; 13(8):895-8 .M Adolescence; Adult; Contraceptives, Oral/*AE/CT; Diabetes Mellitus/*CO; Diabetic Retinopathy/CI/EP/ET; Female; Follow-Up Studies; Human; Hyperglycemia/CO; Hypertension/CI/EP/ET; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Oral contraceptives in women with diabetes. .P JOURNAL ARTICLE. .W We evaluated the association of oral contraceptive use with the presence and severity of diabetic retinopathy, hypertension, and glycosylated hemoglobin in women of childbearing age who have diabetes. Neither current or past use nor number of years of use of oral contraceptives was associated with severity of retinopathy, hypertension, or current glycosylated hemoglobin. In conclusion, further study of various birth control methods in young women of childbearing age should be considered. .A Klein BE; Moss SE; Klein R. .I 274944 .U 91005697 .S Diabetes Care 9101; 13(8):898-900 .M Blood Glucose/*AN; Comparative Study; Cross-Sectional Studies; Diabetes Mellitus/BL/*DI/EP; Glucose Tolerance Test/MT; Hemoglobin A, Glycosylated/*AN; Hexosamines/*BL; Human. .T Comparison of HbA1 and fructosamine in diagnosis of glucose-tolerance abnormalities. .P JOURNAL ARTICLE. .W Total glycosylated hemoglobin (HbA1) and fructosamine were evaluated as screening tools for detection of glucose-tolerance abnormalities in 144 asymptomatic subjects undergoing a 75-g oral glucose tolerance test. Subjects were classified according to World Health Organization criteria as having normal (n = 78), impaired (n = 40), or diabetic (n = 26) glucose tolerance. We found good specificity for HbA1 and fructosamine (100 and 97%, respectively) but low sensitivity (15 and 19%, respectively). At the intersection of the curves of sensitivity and specificity drawn from various thresholds of normality, both sensitivity and specificity were 75% for HbA1 and 55% for fructosamine. Thus, neither HbA1 nor fructosamine seems to be suitable for the diagnosis of mild abnormalities in glucose tolerance. .A Guillausseau PJ; Charles MA; Paolaggi F; Timsit J; Chanson P; Peynet J; Godard V; Eschwege E; Rousselet F; Lubetzki J. .I 274945 .U 91005698 .S Diabetes Care 9101; 13(8):901-2 .M Adult; Case Report; Compulsive Personality Disorder/DI/EP/ET; Diabetes Mellitus, Insulin-Dependent/CO/*PX; Human; Male; Patient Education/*; Risk Factors. .T Emotional side effects of diabetes educational program [letter; comment] .P COMMENT; LETTER. .A Conget JI; Esmatjes E; Ferrer J; De Pablo J; Gomis R. .I 274946 .U 91005699 .S Diabetes Care 9101; 13(8):902-3 .M Adolescence; Blood Glucose/AN; Blood Glucose Self-Monitoring/MT; Child; Child, Preschool; Diabetes Mellitus, Insulin-Dependent/BL/*DT; Human; Infant; Insulin/TU; Michigan; Primary Health Care/*. .T Pediatric primary care for children with IDDM [letter; comment] .P COMMENT; LETTER. .A Clarke WL; Snyder AL. .I 274947 .U 91005700 .S Diabetes Care 9101; 13(8):903 .M Diabetes Mellitus/*EP; Human; Military Personnel/*; Prejudice; United States. .T Change in army policy [letter; comment] .P COMMENT; LETTER. .A Kussman MJ; Clement SC. .I 274948 .U 91005701 .S Diabetes Care 9101; 13(8):904 .M Blood Glucose/*AN; Caucasoid Race/GE; Diabetes Mellitus/BL/GE; Female; Glucose Tolerance Test; Human; Maternal-Fetal Exchange/*; Pregnancy; Pregnancy in Diabetes/*BL; Pregnancy Outcome/GE. .T Relationship of maternal and fetal outcome to glucose tolerance during pregnancy in whites and Indian Asians [letter] .P LETTER. .A Burden AC; Samanta AK. .I 274949 .U 91005702 .S Diabetes Care 9101; 13(8):904-5 .M Anemia, Hemolytic/*CI/ET; Case Report; Diabetes Mellitus, Non-Insulin-Dependent/CO/DT; Female; Human; Middle Age; Sulfonylurea Compounds/*AE/TU. .T Hemolytic anemia associated with sulfonylurea use. Case study and review of literature [letter] .P LETTER. .A Abbate SL; Hoogwerf BJ. .I 274950 .U 91005703 .S Diabetes Care 9101; 13(8):906-7 .M Administration, Oral; Adult; Animal; Case Report; Diabetes Mellitus/*CO/DT; Diagnosis, Differential; Diarrhea/DT/ET/*PS; Human; Male; Metronidazole/AD/TU; Protozoa/*IP; Protozoan Infections/*CO/DI/DT. .T Blastocystis hominis treatable cause of diabetic diarrhea [letter] .P LETTER. .A Sheehan JP; Ulchaker MM. .I 274951 .U 91005704 .S Diabetes Care 9101; 13(8):907-8 .M Adolescence; Adult; Blood Glucose/*AN; Female; Glucose Tolerance Test; Human; Male; Medicine, Traditional; Support, Non-U.S. Gov't; Tea/*. .T Effect of tea prepared from leaves of Syzygium jambos on glucose tolerance in nondiabetic subjects [letter] .P CLINICAL TRIAL; LETTER; RANDOMIZED CONTROLLED TRIAL. .A Teixeira CC; Fuchs FD; Blotta RM; Knijnik J; Delgado IC; Netto MS; Ferreira E; Costa AP; Mussnich DG; Ranquetat GG; et al. .I 274952 .U 91005705 .S Diabetes Care 9101; 13(8):908-9 .M Clinical Protocols/ST; Diabetic Retinopathy/*DI/PA/PC; Human; Mass Screening/ST; Physicians, Family/*; Support, U.S. Gov't, P.H.S.. .T Diabetic eye disease detection by primary-care physicians [letter] .P LETTER. .A Baker SB; Vallbona C; Campbell JV; Hamill MB; Goetz B; West MS. .I 274953 .U 91005706 .S Diabetes Care 9101; 13 Suppl 3:1-58 .M Human; Sulfonylurea Compounds/*; Support, Non-U.S. Gov't. .T Sulfonylurea drugs: basic and clinical considerations. A symposium presented before the 13th International Diabetes Federation Congress. Sydney, Australia, 20 November 1988. Proceedings. .P MEETING REPORT; OVERALL. .I 274954 .U 91005707 .S Diabetes Care 9101; 13 Suppl 3:18-25 .M Diabetes Mellitus, Non-Insulin-Dependent/CO/DT; Human; Structure-Activity Relationship; Sulfonylurea Compounds/AE/*TU. .T Sulfonylureas. Why, which, and how? .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Although controversies remain as to the usefulness of sulfonylureas, most evidence is in favor of their use in many if not patients with non-insulin-dependent diabetes mellitus. When used properly, sulfonylureas improve insulin secretion and action, and these effects may be maintained for years. If combined with hypocaloric dietary regulation, rapid- and short-acting sulfonylureas may help patients reach and maintain euglycemia without provoking chronic hyperinsulinemia or weight increase. There is no evidence that sulfonylurea treatment causes beta-cell exhaustion; instead, the antihyperglycemic effect helps improve beta-cell function. Sulfonylurea "failures" are often dietary failures or may be due to late introduction of these drugs, i.e., when beta-cell function is already attenuated. Desensitization of the insulinotropic effect of sulfonylureas may occur but might be avoided by discontinuous (less than 24 h/day) sulfonylurea exposure, i.e., once-daily administration of a short-acting sulfonylurea in a moderate dose. The most important adverse effect of sulfonylureas is long-lasting hypoglycemia, which may lead to permanent neurological damage and even death. This is mainly seen in elderly subjects who are exposed to some intercurrent event, e.g., acute energy deprivation or a drug interaction, i.e., aspirin. Long-acting sulfonylureas may be more likely to promote long-lasting hypoglycemia. The dose-response relationships of sulfonylureas have been poorly investigated, and sulfonylurea therapy should always be initiated and maintained at the lowest possible dose. .A Melander A; Lebovitz HE; Faber OK. .I 274955 .U 91005708 .S Diabetes Care 9101; 13 Suppl 3:2-8 .M Animal; Cell Membrane/ME/PH/UL; Insulinoma/ME/PA/UL; Islets of Langerhans/ME/PA/*UL; Pancreatic Neoplasms/ME/PA/UL; Rats; Receptors, Drug/*AN/ME/PH; Sulfonylurea Compounds/ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured. .T Characterization and significance of sulfonylurea receptors. .P JOURNAL ARTICLE. .W This study describes and characterizes a putative sulfonylurea receptor. The radioligand used was [3H]glipizide (9 Ci/mmol). The beta-cell plasma membranes were derived from a transplantable rat insulinoma generated by subcutaneous injection of RINm5F cells and purified by ultracentrifugation on a 15-55% sucrose gradient. Specific binding of [3H]glipizide to purified beta-cell plasma membranes was determined to be maximal at temperatures of 4-23 degrees C, pH 7.3, and an incubation of 2 h. Scatchard analysis indicated a single binding site with Kd = 7 nM and sulfonylurea binding of 0.93 pmol/mg membrane protein. Displacement of [3H]glipizide from the purified beta-cell plasma membranes by various sulfonylureas and their analogues correlated well with their known hypoglycemic and insulin-releasing activities. Various agents, including nutrients, agents affecting Ca2+ flux, gastrointestinal hormones, and pancreatic hormones, had no effect on [3H]glipizide binding to the beta-cell plasma membranes. Putative sulfonylurea receptors on beta-cell and brain cell plasma membranes have been reported by several groups of investigators. Sulfonylurea binding to the beta-cell is hypothesized to close an ATP-sensitive K+ channel, which leads to depolarization of the membrane and activation of a voltage-dependent Ca2+ channel. .A Siconolfi-Baez L; Banerji MA; Lebovitz HE. .I 274956 .U 91005710 .S Diabetes Care 9101; 13 Suppl 3:32-6 .M Aged; Carbohydrates/*ME; Diabetes Mellitus, Non-Insulin-Dependent/*DT/ME; Human; Hypoglycemic Agents/*PD; Lipids/*ME; Middle Age; Sulfonylurea Compounds/*TU; Trisaccharides/*PD. .T Effect of acarbose on carbohydrate and lipid metabolism in NIDDM patients poorly controlled by sulfonylureas. .P JOURNAL ARTICLE. .W The ability of acarbose to lower plasma glucose concentration was studied in 12 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were poorly controlled by diet plus sulfonylurea drugs. Patients were studied before and 3 mo after the addition of acarbose to their treatment program, and a significant improvement in glycemic control was noted. Although the decrease in fasting plasma glucose concentration was modest (12.0 +/- 0.8 to 10.8 +/- 0.3 mM), average postprandial plasma glucose concentration decreased by 3.4 mM. When acarbose therapy was discontinued in 5 patients, plasma glucose levels rapidly returned toward pretreatment levels. In addition to the improvement in glycemia, acarbose treatment also led to a significant reduction in HbA1c (7.4 +/- 0.2 to 6.4 +/- 0.2%, P less than 0.01) and triglyceride (2.4 +/- 0.1 to 2.1 +/- 0.1 mM, P less than 0.01) concentrations. Neither the plasma insulin response to meals nor insulin-stimulated glucose uptake improved with acarbose therapy, consistent with the view that acarbose improves glycemic control by delaying glucose absorption. Considerable individual variation was noted in the response to acarbose, and the results in 4 patients were dramatic, with striking reductions in both fasting and postprandial glucose concentrations. The addition of acarbose to patients with NIDDM not well controlled by sulfonylureas appears to have significant clinical benefit. .A Reaven GM; Lardinois CK; Greenfield MS; Schwartz HC; Vreman HJ. .I 274957 .U 91005711 .S Diabetes Care 9101; 13 Suppl 3:37-41 .M Adult; Aged; Biguanides/*TU; Diabetes Mellitus, Non-Insulin-Dependent/*DT; Drug Therapy, Combination; Human; Lipids/*ME; Middle Age; Sulfonylurea Compounds/*TU. .T Biguanides and sulfonylureas as combination therapy in NIDDM. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Oral combination therapy with biguanides (metformin) and sulfonylureas is discussed. The rationale for the use of this combination is based on the different sites of action of the two kinds of drugs and the possibility for obtaining additive or potentiating effects and reduced side effects. The clinical usefulness of chlorpropamide and glyburide in combination with metformin has been demonstrated in some clinical trials. The combination may provide satisfactory glycemic control for several years, and possibly insulin therapy can be postponed or even avoided. No special safety problems are encountered with the use of the combination other than those attributed to the use of metformin or sulfonylurea alone, i.e., lactic acidosis and hypoglycemia, respectively. The lethality risks of these associated conditions are comparable. It is concluded that more data are needed to evaluate the full clinical potential and the mechanism of action of oral combination therapy. .A Hermann LS. .I 274958 .U 91005712 .S Diabetes Care 9101; 13 Suppl 3:42-6 .M Administration, Oral; Adult; Blood Glucose/ME; Diabetes Mellitus, Non-Insulin-Dependent/*DT/ME; Double-Blind Method; Drug Therapy, Combination; Female; Glipizide/AD/PD/*TU; Human; Hyperglycemia/DT/ME; Injections, Subcutaneous; Male; Middle Age; Proinsulin/AD/PD/*TU; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Metabolic effects of combination glipizide and human proinsulin treatment in NIDDM. .P JOURNAL ARTICLE. .W The effects of 3 mo of treatment with a combination of glipizide and human proinsulin were studied in a small group of closely monitored patients. The patients had non-insulin-dependent diabetes mellitus (NIDDM) and poor glucose regulation, despite maximal sulfonylurea therapy. This was a randomized double-blind placebo-controlled trial in which there were three treatment groups who received either 20 mg glipizide given 30 min before breakfast and dinner and human proinsulin given subcutaneously at bedtime (n = 5), glipizide and human proinsulin placebo (n = 5), or glipizide placebo and human proinsulin (n = 5). Glycemic regulation was assessed by measurements of 24-h plasma glucose profiles and glycosylated hemoglobin. Our observations demonstrate that the combination of glipizide plus human proinsulin was more effective than either agent alone in controlling overall glycemia in patients with NIDDM. The data support the concept of use of an agent during the day that has its major effects postprandially and another agent at bedtime that is relatively hepatospecific. .A Pasmantier R; Chaiken RL; Hirsch SR; Lebovitz HE. .I 274959 .U 91005713 .S Diabetes Care 9101; 13 Suppl 3:47-52 .M Diabetes Mellitus, Non-Insulin-Dependent/*DT; Drug Therapy, Combination; Human; Insulin/*TU; Sulfonylurea Compounds/*TU; Support, Non-U.S. Gov't. .T Combined insulin-sulfonylurea therapy in treatment of NIDDM. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W For the past few years, interest has focused on the combination of insulin and sulfonylurea in the search for effective treatments for non-insulin-dependent diabetes mellitus (NIDDM) patients who fail on oral hypoglycemic agents. Although several studies have demonstrated beneficial effects of such therapy in NIDDM patients, the average effect is small and is observed in only about half of the patients. However, there are several problems with most previous studies, including small sample size, selection of patients, and simultaneous use of several end points. First, residual beta-cell function has been considered to be a prerequisite for a beneficial effect of combination therapy. Therefore, most studies have failed to demonstrate improved glycemic control after adding sulfonylurea to insulin therapy in patients with insulin-dependent diabetes mellitus. Inclusion of patients with impaired beta-cell function will therefore attenuate the effect of combination therapy. Second, most studies have used glycemic control as an end point. Nevertheless, the insulin dose has been reduced by 20-30% to avoid hypoglycemia after adding sulfonylurea to insulin. Thus, the comparison has been made between treatments with a smaller insulin dose with sulfonylurea and a larger insulin dose without sulfonylurea. The patient most likely to benefit from combination therapy is slightly obese, has had NIDDM for a relatively short period, and has preserved beta-cell function. In such a patient, combined insulin-sulfonylurea therapy predominantly stimulates basal insulin secretion, resulting in more effective suppression of hepatic glucose production and lower fasting plasma glucose. The side effects are few, most notably more frequent but mild hypoglycemic reactions. .A Groop LC; Groop PH; Stenman S. .I 274960 .U 91005714 .S Diabetes Care 9101; 13 Suppl 3:53-8 .M Diabetes Mellitus, Non-Insulin-Dependent/CO/ME/*PC; Glucose/*ME; Glucose Tolerance Test; Human; Sulfonylurea Compounds/*TU. .T Will sulfonylurea treatment of impaired glucose tolerance delay development and complications of NIDDM? .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W The chronic hyperglycemia of non-insulin-dependent diabetes mellitus (NIDDM) evolves gradually and is usually preceded by more transient hyperglycemia, classified as impaired glucose tolerance (IGT). Already in this phase, there is an increased risk of cardiovascular complications, and many IGT subjects, like NIDDM patients, often display several of the metabolic and circulatory disturbances that are associated with hyperglycemia, e.g., insulin resistance, hyperinsulinemia and/or hyperproinsulinemia, delayed insulin release, dyslipidemia, and hypertension. Therefore, and because untreated hyperglycemia is a self-perpetuating condition, early detection and early intervention may be necessary to prevent the progression and complications of NIDDM. This in turn would necessitate screening procedures, and the therapeutic goal should include both euglycemia and normalization of plasma insulin, plasma lipids, and blood pressure. A study in the German Democratic Republic indicated that the mortality in screening-detected NIDDM patients did not differ from that in patients detected in routine care. In a Swedish study on screening-detected NIDDM subjects, only those who had IGT rather than manifest NIDDM could maintain fasting blood glucose less than or equal to 6 mM for 5 yr by hypocaloric dietary regulation alone. In those with screening-detected NIDDM, the delayed acute insulin release and net postprandial hyperglycemia were improved by addition of glipizide, and most managed to attain and maintain fasting blood glucose less than or equal to 6 mM for approximately 2 yr after such addition. However, after 4 yr, there was an increase in blood glucose, suggesting that preventive intervention either may not be possible or may have to start in the IGT phase.(ABSTRACT TRUNCATED AT 250 WORDS) .A Melander A; Bitzen PO; Sartor G; Schersten B; Wahlin-Boll E. .I 274961 .U 91005715 .S Diabetes Care 9101; 13 Suppl 3:9-17 .M Human; Insulin/*ME; Pancreas/ME; Sulfonylurea Compounds/*PD; Support, Non-U.S. Gov't. .T Mechanisms of sulfonylurea-induced insulin release. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W The mechanisms responsible for the stimulation of insulin release from the pancreatic beta-cell by hypoglycemic sulfonylureas are reviewed herein. One hypothesis postulates that these agents act, at the level of the plasma membrane, by causing the closure of a class of K+ channels characterized by their sensitivity to ATP. This may lead to depolarization of the plasma membrane, gating of voltage-sensitive Ca2+ channels, increase in cytosolic Ca2+ activity, and activation of the effector system for insulin release. However, it is not evident that the closure of ATP-sensitive K+ channels accounts for effects of sulfonylureas such as inhibition of K+ inflow into the islet cells, increase in their Na+ content, or even stimulation of Ca2+ inflow and insulin release at physiological or higher concentrations of D-glucose. .A Malaisse WJ; Lebrun P. .I 274962 .U 91005728 .S Dis Mon 9101; 36(10):537-91 .M Adult; Diagnosis, Differential; Female; Human; Psychotherapy; Somatoform Disorders/DI/*TH. .T Managing somatization disorder. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Somatization disorder (SD), a chronic psychiatric illness that affects about 1% of adult women, is characterized by multiple somatic complaints. It should be suspected in any woman who presents with a vague or complicated history; unaccountable non-responsiveness to therapy; dramatic, seductive or demanding personality style; family history of personality disorder; sexual abuse as a child; substance abuse; or depression with atypical features. Its cause is unknown, although both genetic and environmental factors have been implicated. At follow-up, patients with SD continue to have somatic symptoms, but many improve with therapy. Nearly two thirds of patients with SD attempt suicide, but few complete it; however, completions may be more common than formerly realized. There is no specific treatment for SD, but management can be organized around the following ABCs: Accommodate initially to forge rapport; Behavior modification (ignore symptoms, praise for improved behavior); Confrontation later about effects of behavior style; Decrease drugs gradually, with praise for reduction; Educate about course and meaning of illness; Family involvement to give information and help with treatment; Guilt should be assuaged in physicians, who may blame themselves when patients do not improve; Hospitalize (closed psychiatric unit) only for serious suicide risk, substance abuse, or other extreme behavior; and Intercurrent depression should be treated conservatively. .A Morrison J. .I 274963 .U 91005729 .S Dis Mon 9101; 36(11):593-637 .M Diagnosis, Differential; Human; Myasthenia Gravis/*/DI/IM/TH. .T Myasthenia gravis. .P JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC. .W Myasthenia Gravis is a disorder of neuromuscular function resulting from an immunologically based premature destruction of acetylcholine receptors. The disease is characterized clinically by variable weakness accentuated by repetitive muscular activity and usually responding to the administration of acetylcholinesterase inhibitors. Myasthenia Gravis is a complex disease and requires understanding of the many facets of its natural history and immunological basis to ensure optimal individual patient management. The long-term goal is control of the immunological imbalance; treatment regimens include thymectomy, corticosteroids, azathioprine, and plasmapheresis. The common use of acetylcholinesterase inhibitors provides symptomatic relief during variable daily muscular activity. Disability due to myasthenia gravis is to a large extent reversible and death is preventable. Early recognition of myasthenia gravis and appropriate treatment are often rewarded by remission that may be permanent. .A Linton DM; Philcox D. .I 274964 .U 91006586 .S Fertil Steril 9101; 54(4):559-73 .M Abortion/*; Amenorrhea/CI; Chromosome Abnormalities/CI; Contraceptives, Oral/*AE; Female; Fertility/*; Fetal Diseases/CI; Human; Intrauterine Devices/*; Pregnancy; Spermatocidal Agents/AE; Uterine Diseases/ET; Virilism/CI. .T Fertility after contraception or abortion. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W There is a very small correlation, if any, between the prior use of OCs and congenital malformations, including Down's syndrome. There are few, if any, recent reports on masculinization of a female fetus born to a mother who took an OC containing 1 mg of a progestogen during early pregnancy. However, patients suspected of being pregnant and who are desirous of continuing that pregnancy should not continue to take OCs, nor should progestogen withdrawal pregnancy tests be used. Concern still exists regarding the occurrence of congenital abnormalities in babies born to such women. The incidence of postoperative infection after first trimester therapeutic abortion in this country is low. However, increasing numbers of women are undergoing repeated pregnancy terminations, and their risk for subsequent pelvic infections may be multiplied with each succeeding abortion. The incidence of prematurity due to cervical incompetence or surgical infertility after first trimester pregnancy terminations is not increased significantly. Asherman's syndrome may occur after septic therapeutic abortion. The pregnancy rate after treatment of this syndrome is low. The return of menses and the achievement of a pregnancy may be slightly delayed after OCs are discontinued, but the fertility rate is within the normal range by 1 year. The incidence of postpill amenorrhea of greater than 6 months' duration is probably less than 1%. The occurrence of the syndrome does not seem to be related to length of use or type of pill. Patients with prior normal menses as well as those with menstrual abnormalities before use of OCs may develop this syndrome. Patients with normal estrogen and gonadotropin levels usually respond with return of menses and ovulation when treated with clomiphene. The rate for achievement of pregnancy is much lower than that for patients with spontaneous return of menses. The criteria for defining PID or for categorizing its severity are diverse. The incidence of PID is higher among IUD users than among patients taking OCs or using a barrier method. The excess risk of PID among IUD users, with the exception of the first few months after insertion, is related to sexually transmitted diseases and not the IUD. Women with no risk factors for sexually transmitted diseases have little increased risk of PID or infertility associated with IUD use. There appears to be no increased risk of congenital anomalies, altered sex ratio, or early pregnancy loss among spermicide users. All present methods of contraception entail some risk to the patient. The risk of imparied future fertility with the use of any method appears to be low.(ABSTRACT TRUNCATED AT 400 WORDS) .A Huggins GR; Cullins VE. .I 274965 .U 91006587 .S Fertil Steril 9101; 54(4):574-6 .M Endoscopy/MT/*TD; Fallopian Tubes/*PA; Female; Human. .T Falloposcopy: frontiers realized ... a fantastic voyage revisited [editorial] .P EDITORIAL. .A Corfman RS. .I 274966 .U 91006588 .S Fertil Steril 9101; 54(4):577-9 .M Cervix Mucus/*ME/PH; Clomiphene/*AE; Estrogens/*TU; Female; Human; Support, Non-U.S. Gov't; Viscosity. .T Exogenous estrogen therapy for treatment of clomiphene citrate-induced cervical mucus abnormalities: is it effective? [see comments] .P JOURNAL ARTICLE. .W Clomiphene citrate (CC) may have an adverse effect on cervical mucus (CM) quality and quantity. A placebo-controlled study was performed to assess the effect of exogenous follicular phase estrogen (E) on CM. Subjects qualified for inclusion by repeated demonstration of poor CM while on CC therapy as judged by spinnbarkeit, quantity, and viscosity. Subjects were treated by a randomized, placebo-controlled format using: (1) oral micronized estradiol (E2), 2 mg; (2) conjugated Es, 5 mg, or (3) placebo administered on cycle days 9 to 14. Cervical mucus was scored blindly during therapy within 48 hours before ovulation. Twelve subjects were observed through 36 treatment cycles with mean (+/- SD) CM scores: micronized E2, 4.2 +/- 1.8; conjugated Es, 4.3 +/- 1.7; and placebo, 4.7 +/- 2.9. There was no significant difference in mean values (P = 0.96, analysis of variance) or frequency of CM score greater than 4 (P = 0.85, Fisher exact test). We conclude that therapy with the E preparations tested did not improve the quality or quantity of CM in CC-treated patients. .A Bateman BG; Nunley WC Jr; Kolp LA. .I 274967 .U 91006589 .S Fertil Steril 9101; 54(4):580-4 .M Epinephrine/*AD; Fallopian Tubes; Female; Follow-Up Studies; Gonadotropins, Chorionic/BL; Human; Injections; Length of Stay; Methotrexate/AE/*TU; Osmolar Concentration; Pregnancy; Pregnancy, Tubal/BL/*DT; Uterus. .T Treatment of tubal pregnancy by local injection of methotrexate after adrenaline injection into the mesosalpinx: a report of 25 patients. .P JOURNAL ARTICLE. .W Twenty-five patients with a tubal pregnancy were treated by an injection of methotrexate (MTX) into the tubal swelling after vasoconstriction of the mesosalpinx with adrenaline. Twenty-four of the 25 patients had an uneventful clinical course. In one case, the tube ruptured despite falling serum human chorionic gonadotropin (hCG) concentrations. In 17 of 24 patients, the dose of 100 mg that was locally injected was sufficient. Seven patients were given additional systemic injections. In 3 of the 4 patients with high initial serum hCG levels (greater than 10.000 mIU/mL), the clinical course was uneventful. The side effects of MTX and adrenaline were minimal. Whether this way of treatment guarantees better chances of fertility in the future is unknown. Therefore a prospective, case-controlled study comparing the fertility rates in different ways of treatment is needed. .A Kooi S; Kock HC. .I 274968 .U 91006590 .S Fertil Steril 9101; 54(4):585-9 .M Comparative Study; Drug Therapy, Combination; Estradiol/BL; Female; Gonadotropins/*TU; Human; Menstrual Cycle/BL; Metoclopramide/*TU; Ovulation Induction; Polycystic Ovary Syndrome/*DT; Prolactin/BL. .T The effect of metoclopramide on ovarian responsiveness to gonadotropin administration in patients with severe polycystic ovarian syndrome. .P CLINICAL TRIAL; JOURNAL ARTICLE. .W Six patients with poor ovarian response to menotropin after pretreatment with a gonadotropin-releasing hormone analog exhibited improved ovarian responsiveness when metoclopramide was added on days 3, 5, and 7 of the cycle. This was evidenced by a higher number of leading follicles (4.4 versus 0.6), a higher mean of maximal serum 17 beta-estradiol levels (560 versus 178 pg/mL), a shorter duration of menotropin treatment (7 versus 11 days), and fewer ampules of menotropin used (20 versus 37 ampules/cycle) in metoclopramide-treated cycles as compared with control cycles, respectively. Serum prolactin levels reached a maximum of 172 ng/mL within 1 hour after metoclopramide administration and declined to normal range within 6 hours. These results suggest that intermittent increased prolactin secretion may augment ovarian response to gonadotropins. .A Lissak A; Dirnfeld M; Sorokin Y; Kahana L; Abramovici H; Koch Y. .I 274969 .U 91006592 .S Fertil Steril 9101; 54(4):597-600 .M Androstenedione/PD; Aromatase/*ME; Body Fluids/ME; Comparative Study; Dexamethasone/*TU; Female; Graafian Follicle/ME; Granulosa Cells/*EN; Human; Polycystic Ovary Syndrome/*DT/EN; Reference Values; Sex Hormones/ME. .T Aromatase activity of human granulosa cells in patients with polycystic ovaries treated with dexamethasone. .P JOURNAL ARTICLE. .W The effect of dexamethasone (DEX) (9 alpha-Fluro-16 alpha-methyl prednisolone) on secretion of steroids by human granulosa luteinized cells was studied by culturing cells from mature follicles of women with polycystic ovarian disease and treated for infertility in the in vitro fertilization program. Patients were treated with DEX 0.5 mg/d until the day of human chorionic gonadotropin administration. The cells were cultured for 24 hours in the presence of androstenedione (10(-7)M). After incubating for 24 hours, the medium was replaced and the cells were incubated for an additional 24 hours. The medium was then harvested and assayed for estradiol (E2) and progesterone (P). Results were compared with those of a control group who was not treated with DEX. Estradiol production by cells was significantly lower in the study group treated with DEX. Progesterone production was not influenced by DEX. Follicular fluid levels, E2, and androgens did not vary with DEX treatment, whereas cortisol levels markedly decreased and P levels increased with the treatment. These findings suggest that glucocorticosteroids can directly influence granulosa luteinized cell function. .A Bider D; Pariente C; Dor J; Zolti M; Mashiach S; Ben-Rafael Z. .I 274970 .U 91006593 .S Fertil Steril 9101; 54(4):601-5 .M Adult; Binding, Competitive; Clomiphene/*PD; Corpus Luteum/AH/*ME; Cytosol/ME; Female; Human; Hydroxyprogesterones/ME; Menstrual Cycle/DE/*ME; Organ Weight/DE; Osmolar Concentration; Progesterone/ME; Receptors, LH/*ME; Support, Non-U.S. Gov't. .T Luteinizing hormone and human chorionic gonadotropin receptors in human corpora lutea from clomiphene citrate-induced cycles. .P JOURNAL ARTICLE. .W Midluteal phase corpora lutea (CL) obtained from women induced with 50 mg (n = 5), 100 mg (n = 5), and 150 mg (n = 5) of clomiphene citrate (CC) were measured for luteinizing hormone/human chorionic gonadotropin (LH/hCG) concentrations and cytosol progesterone (P) and 17 alpha-hydroxyprogesterone (17-OHP) and compared with midluteal phase CL from eight normal women (controls). More CL (26) that were significantly heavier (2.0 +/- 0.3 g, [mean +/- SEM]) were obtained with CC than in controls (10). Clomiphene citrate treatment increased LH/hCG receptor concentrations and the dissociation constant significantly from 69 +/- 12 fmol/mg protein and 1.1 +/- 0.2 x 10(-10) M, respectively, in controls to 112 +/- 6 fmol/mg protein and 2.1 +/- 0.1 X 10(-10) M. Cytosol P and 17-OHP levels were not significantly increased. Cumulatively these cellular effects may be responsible for increasing serum P and responsiveness to hCG and for correcting luteal dysfunction. .A Yeko TR; Khan-Dawood FS; Dawood MY. .I 274971 .U 91006594 .S Fertil Steril 9101; 54(4):606-11 .M Body Fluids/*ME; Carotene/ME; Cleavage Stage, Ovum/*; Female; Fertilization in Vitro/*; Graafian Follicle/*ME; Human; Osmolar Concentration; Proteins/*ME; Sex Hormones/*ME; Spectrophotometry. .T Spectrophotometric analysis of follicular fluid related to oocyte fertilization, embryo cleavage, and follicular fluid protein and hormone content. .P JOURNAL ARTICLE. .W Spectrophotometric absorbance patterns of follicular fluids (FF) obtained from in vitro fertilization patients were analyzed and compared with oocyte fertilization and embryo cleavage rates. Each absorbance pattern was resolved into three components: delta OD360, delta OD415, and delta OD455. A positive correlation was found between fertilization outcome and delta OD455. The absorbances were not related to embryo cleavage rates. We confirmed the presence of bilirubin and beta-carotene in FF: these pigments absorb at 455 nm and are most likely serum-derived. To explain the association between delta OD455 and fertilization, we hypothesized that the FF delta OD455 is a marker of the degree of vascularization of the follicle that could be assessed by FF protein and hormone concentrations. However, no correlation was found between the delta OD455 and these FF parameters, suggesting an alternative explanation for this association. .A Bayer SR; Ransil BJ; Shelton SJ; Armant DR. .I 274972 .U 91006595 .S Fertil Steril 9101; 54(4):612-8 .M Adult; Circadian Rhythm; Female; Human; LH/*BL; Melatonin/BL/*PH; Ovulation/*PH; Radioimmunoassay/MT. .T Melatonin and the ovulatory luteinizing hormone surge [see comments] .P JOURNAL ARTICLE. .W A newly developed 125I-radioimmunoassay allows for the accurate determination of physiological concentrations of plasma melatonin. Melatonin secretion does not change significantly on the day before and the day of the luteinizing hormone (LH) surge when compared with the early follicular phase. In addition, it was confirmed that the beginning of the LH surge frequently occurs in the morning and is associated with low melatonin values (six of nine women). Supraphysiological melatonin concentrations did not decrease the midcycle LH secretion in four women studied. .A Zimmermann RC; Schroder S; Baars S; Schumacher M; Weise HC. .I 274973 .U 91006596 .S Fertil Steril 9101; 54(4):619-23 .M Abortion, Habitual/*TH; Antibodies/*AN; Cardiolipins/*IM; Enzyme-Linked Immunosorbent Assay; Female; Human; IgG/AN; IgM/AN; Immunization/*; Pregnancy; Reference Values. .T Serum levels of anticardiolipin antibodies are pathologically increased after active immunization of patients with recurrent spontaneous abortion. .P JOURNAL ARTICLE. .W Although the pathophysiological mechanisms leading to recurrent spontaneous abortion are still not fully understood, treatment schemes based on immunological principles have been advocated in recent years claiming that the production of the so-called blocking factor is being specifically stimulated. We investigated, retrospectively, whether active immunization can affect the production of immunoglobulin (Ig)G and IgM anticardiolipin antibodies. In a group of untreated recurrent spontaneous abortion patients (n = 9), the range of variation of cardiolipin antibodies, during consecutive controls taken at the same time interval as after immunization, was not statistically significant. In contrast to this, significant increases of both IgG and IgM antibodies occurred after active immunization with paternal leucocytes in 10 of 15, and in 6 of 15 cases, respectively. The mean basal and posttransfusion levels were: 7.26 +/- 2.53 and 30.15 +/- 23 U/mL for IgG and 2.26 +/- 1.2 and 6.82 +/- 5.6 U/mL for IgM, respectively. We conclude that active immunization with human lymphocytes leads to the production of antibodies against cardiolipin. This effect is exerted on both IgM and IgG antibodies. .A Moncayo R; Moncayo H; Steffens U; Soelder E; Kersting A; Dapunt O. .I 274974 .U 91006597 .S Fertil Steril 9101; 54(4):624-31 .M Adult; Antigens/*AN; Antigens, Neoplasm/AN; Antigens, Surface/AN; Endometrium/CY/*IM; Female; Human; HLA-DR Antigens/AN; Immunologic Techniques; Integrins/IM; Membrane Glycoproteins/AN; Menstrual Cycle/*IM; Middle Age; Stains and Staining; Support, U.S. Gov't, P.H.S.. .T Immunoreactivity of human endometrium: correlation with endometrial dating [see comments] .P JOURNAL ARTICLE. .W Human leukocyte antigen (HLA)-DR molecules of the major histocompatibility complex II, very late antigen-1 of the integrin superfamily of molecules, B72.3 (a tumor-associated glycoprotein), Ki67 (a marker of proliferation), and epithelial membrane antigen (EMA, a high molecular weight glycoprotein) were found to have distinctive localization within endometrium throughout the menstrual cycle. These molecules were localized by avidin-biotin-complex procedure in 26 endometria dated to midproliferative, late proliferative, early secretory, midsecretory, and late secretory phases of the menstrual cycle. Proliferative phase of the menstrual cycle was characterized by expression of Ki67 and HLA-DR and absence of very late antigen-1, B72.3, and EMA in endometrial glands. Secretory phase of the menstrual cycle was marked by the appearance and persistence of very late antigen-1, B72.3, and EMA in glandular epithelium. In addition, the solid compactum of the late secretory phase was marked by the development of very late antigen-1 in the predecidual cells. These findings demonstrate that the immunoreactivity of human endometrium is under the same constraints that compel the endometrium to undergo morphological changes. .A Tabibzadeh S. .I 274975 .U 91006598 .S Fertil Steril 9101; 54(4):632-7 .M Adult; Body Composition; Dietary Fats/*AN; Dietary Fiber/*AN; Female; Hormones/UR; Human; Nutrition; Oligomenorrhea/*ET/UR; Risk Factors; Stress, Psychological; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T High dietary fiber and low saturated fat intake among oligomenorrheic undergraduates. .P JOURNAL ARTICLE. .W Numerous functional risk factors are associated with the occurrence of secondary amenorrhea in young women. Less is known regarding factors associated with the more prevalent problem of oligomenorrhea. We have evaluated nutrient intake, body composition, perceived psychological stress, 24-hour urinary cortisol, and urinary C peptide (UCP) in 35 eumenorrheic, 11 mildly oligomenorrheic, and 10 oligomenorrheic nonathletic undergraduate women. Nutrient intake was evaluated by a validated food frequency questionnaire. Oligomenorrheic women were found to consume significantly more dietary fiber, crude fiber, and polyunsaturated fat, and significantly less saturated fat than their eumenorrheic classmates. Oligomenorrheic women had significantly lower 24-hour UCP excretion than mildly oligomenorrheic women. The groups did not differ in any aspect of body composition, body weight, age of menarche, perceived psychological stress, or urinary cortisol excretion. The data suggest that higher intake of fiber and lower intake of saturated fat may be associated with oligomenorrhea among otherwise healthy undergraduate nonathletic women. .A Snow RC; Schneider JL; Barbieri RL. .I 274976 .U 91006599 .S Fertil Steril 9101; 54(4):638-42 .M Adult; Female; Graafian Follicle/*GD; Human; Menstrual Cycle/*PH; Ovary/*PH; Reference Values; Reproducibility of Results; Support, Non-U.S. Gov't. .T Growth patterns of nondominant ovarian follicles during the normal menstrual cycle. .P JOURNAL ARTICLE. .W Transvaginal ultrasound examinations were performed in seven normally cycling women to characterize growth of nondominant follicles in both ovaries. Mean follicle number showed little variation throughout the menstrual cycle with no differences between dominant and nondominant ovaries. Up to 11 follicles (greater than or equal to 2 mm) were observed in any one ovary. From observations of the first appearance of the dominant follicle (mean size 9.9 +/- 3.0 [SD] mm), selection was assumed to take place on cycle day 6.3 +/- 2.3. The diameter of nondominant follicles always remained less than 11 mm. Growth of small follicles was established in both dominant and nondominant ovaries up to the time of selection. The late follicular and luteal phases were characterized by a decrease in mean growth slopes of nondominant follicles in the dominant ovary only. These observations may provide in vivo evidence for the concept of intraovarian paracrine mechanisms and may have implications for the sonographic diagnosis of anovulation and monitoring of ovulation induction. .A Pache TD; Wladimiroff JW; de Jong FH; Hop WC; Fauser BC. .I 274977 .U 91006601 .S Fertil Steril 9101; 54(4):648-51 .M Biopsy; Endometriosis/*PA; Histological Techniques; Human; Pelvis; Peritoneum/*PA; Reference Values. .T A serial section study of visually normal pelvic peritoneum in patients with endometriosis. .P JOURNAL ARTICLE. .W Defined criteria were used to select small samples of visually normal study peritoneum for serial section light microscopy in 45 patients with biopsy-proven endometriosis and 10 patients without endometriosis. A glandular element compatible with possible endometriosis was found in only 1 patient. Visually normal peritoneum does not harbor a high prevalence of invisible microscopic endometriosis. .A Redwine DB; Yocom LB. .I 274978 .U 91006602 .S Fertil Steril 9101; 54(4):652-5 .M Embryo Transfer; Female; Fertilization in Vitro/*MT; Gamete Intrafallopian Transfer; Gonadorelin/*PH; Human; Menstrual Cycle; Oocytes/*; Ovulation Induction; Pregnancy; Specimen Handling/*; Time Factors. .T The use of gonadotropin-releasing hormone agonist to regulate oocyte retrieval time. .P JOURNAL ARTICLE. .W We investigated the use of a gonadotropin-releasing hormone agonist (GnRH-a) to assist in the synchronous entry of a fixed number of subjects into in vitro fertilization (IVF) and gamete intrafallopian tube transfer cycle. Using a protocol in which a GnRH-a was given in the follicular or luteal phase, the clinical pregnancy rate per procedure was 27%. We conclude that the use of a GnRH-a for synchronous cycles in IVF-embryo transfer is efficacious and results in acceptable pregnancy rates. .A Patton PE; Eaton D; Burry KA; Wolf DP. .I 274979 .U 91006605 .S Fertil Steril 9101; 54(4):665-70 .M Female; Gonadotropins/*PD; Human; Karyotyping; Oocytes/*PH; Ovary/*DE; Ploidies; Support, Non-U.S. Gov't. .T Consequences of high ovarian response to gonadotropins: a cytogenetic analysis of unfertilized human oocytes. .P JOURNAL ARTICLE. .W Several reports have shown decreased fertilization and implantation rates in high-responder patients to gonadotropins. In this cytogenetic study of unfertilized human oocytes, we have investigated possible reasons for this clinical evidence. Three groups of patients were established according to the number of oocytes retrieved: group 1 (n = 21), 1 to 5 oocytes; group 2 (n = 32), 6 to 10 oocytes; and group 3 (n = 35), greater than or equal to 11 oocytes. Patients in group 3 had lower estradiol levels per follicle developed, lower follicular volume, higher incidence of diploid oocytes, and higher rate of oocytes with an additional set of prematurely condensed sperm chromosomes of the presynthetic gap than groups 1 and 2. These results suggest that women with greater than or equal to 11 oocytes retrieved have a relative higher cytoplasmic immaturity that could explain the lower fertilization and implantation rates found in other studies. .A Tarin JJ; Pellicer A. .I 274980 .U 91006606 .S Fertil Steril 9101; 54(4):671-7 .M Dissection; Evaluation Studies; Female; Fertilization in Vitro/*MT; Fetal Development; Human; Microsurgery/MT; Zona Pellucida. .T Clinical evaluation of three approaches to micromanipulation-assisted fertilization. .P JOURNAL ARTICLE. .W Three different micromanipulation procedures were used to assist human fertilization in cases of severe male factor infertility. Zona drilling was performed either with acid Tyrode's solution, mechanically following zona softening with chymotrypsin, or by partial zona dissection. The fertilization rate was lowest in the zona drilling/acid Tyrode's group (7/40; 17.5%), although no differences between groups (zona drilling/chymotrypsin: 21/84, 25%; partial zona dissection: 31/143, 21.7%) were significant. The fertilization rate was significantly increased relative to untreated eggs from the same patients only in the partial zona dissection group (31/143, 21.7% versus 4/102, 3.9%). Oocyte damage occurred at a high rate as a result of zona drilling with acid Tyrode's solution (13/41, 37%). Embryonic development was compromised after zona drilling with chymotrypsin: only 7/12 (58.3%) of the fertilized oocytes cleaved, and the morphology of many of the cleaved embryos was abnormal. Although only 61% (16/26) of the diploid embryos resulting from partial zona dissection cleaved, the embryonic morphology of these embryos was comparable with controls. No pregnancies resulted from the transfer of manipulated embryos. We conclude that although zona manipulation increases the fertilization rate, losses due to oocyte trauma, low rates of diploid fertilization, low rates of cleavage, and a high frequency of abnormal cleavage reduce the number of embryos available for transfer. .A Garrisi GJ; Talansky BE; Grunfeld L; Sapira V; Navot D; Gordon JW. .I 274981 .U 91006607 .S Fertil Steril 9101; 54(4):678-81 .M Adult; Catheterization/IS; Comparative Study; Embryo Transfer/IS/*MT; Female; Fertilization in Vitro/*; Human; Pregnancy. .T Dummy embryo transfer: a technique that minimizes the problems of embryo transfer and improves the pregnancy rate in human in vitro fertilization. .P CLINICAL TRIAL; JOURNAL ARTICLE. .W Three hundred thirty-five patients selected for in vitro fertilization (IVF) were randomly divided into two groups. Group A (n = 167) was subjected to dummy embryo transfer (ET) before the start of IVF treatment to choose the most suitable catheter for each patient. Group B (n = 168) started their IVF treatment without dummy ET. Embryo transfer technique was difficult in 50 cases (29.8%) in group B, whereas no difficulty was met in group A. Pregnancy rate and implantation rate (22.8%, 7.2%) in group A were significantly higher than in group B (13.1%, 4.3%). The lower pregnancy rate in group B is due to the very low pregnancy rate (4%) in difficult ET cases. Dummy ET is a simple procedure that determines the most suitable ET catheter for each patient and avoids unexpected difficult and failed ET. .A Mansour R; Aboulghar M; Serour G. .I 274982 .U 91006608 .S Fertil Steril 9101; 54(4):682-8 .M Adult; Cryopreservation/*; Embryo Transfer/*; Female; Fertilization in Vitro/*; Gonadorelin/PD; Human; Luteal Phase; Oocytes/*; Ovum Implantation/*; Pregnancy; Progesterone/PD; Time Factors; Tissue Donors. .T Different implantation rates after transfers of cryopreserved embryos originating from donated oocytes or from regular in vitro fertilization [see comments] .P JOURNAL ARTICLE. .W Most oocyte donation programs have experienced higher pregnancy rates than usually seen in regular in vitro fertilization (IVF), suggesting that the quality of either the oocytes or the endometrium is superior. To clarify this issue we analyzed the results of transfers of 136 cryopreserved embryos originating either from donated oocytes (18 transfers) or from regular IVF (118 transfers). Transfers of embryos originating from donated oocytes took place after administrating oral estradiol (E2) valerate and vaginal micronized progesterone (P) following a regimen designed to mimic the serum levels of E2 and P observed during the menstrual cycle. Transfers of embryos originating from regular IVF took place either in the natural cycle (53 transfers) or after suppressing ovarian function with a single injection of a gonadotropin-releasing hormone agonist (GnRH-a), Decapeptyl-Retard 3.75 mg, and administering the same hormone replacement regimen (E2/P) used in oocyte donation (65 transfers). Eighteen transfers involving 24 embryos originating from donated oocytes were affected, resulting in six pregnancies (4 ongoing). The ongoing pregnancy rate per transfer was 22%. Seventy-nine embryos originating from regular IVF were transferred (53 transfers) in the natural cycle resulting in six pregnancies (2 ongoing). One hundred three other embryos originating from regular IVF were transferred (65 transfers) after administration of GnRH-a and E2/P resulting in four pregnancies. The pregnancy rate after transfers of embryos originating from regular IVF was 9% per transfer. This was significantly less than the pregnancy rate of 33% per transfer seen after the transfers of embryos originating from donated oocytes.(ABSTRACT TRUNCATED AT 250 WORDS) .A de Ziegler D; Frydman R. .I 274983 .U 91006609 .S Fertil Steril 9101; 54(4):689-93 .M Dose-Response Relationship, Drug; Double-Blind Method; Human; Infertility, Male/*DT; Male; Oligospermia/*DT; Pilot Projects; Semen/ME; Sex Hormones/BL; Support, Non-U.S. Gov't; Testosterone/*AA/AD/TU. .T Treatment of idiopathic testicular failure with high-dose testosterone undecanoate: a double-blind pilot study. .P CLINICAL TRIAL; JOURNAL ARTICLE. .W The effect of high-dose (240 mg/d) intake of testosterone (T) undecanoate was studied for sperm characteristics, function of the accessory sex glands, and hormonal parameters of men with idiopathic oligozoospermia, asthenozoospermia, or teratozoospermia using a two-phase protocol including a 3-month double-blind period followed by a 3-month open phase. Increased sperm viability and semen content of adenosine triphosphate were either not reproducible after patients on placebo were switched over to T undecanoate or did not reach statistical significance, whereas no changes were detected in other sperm characteristics and the accessory sex glands. Intake of T undecanoate significantly increased the concentration of 5-alpha-dihydrotestosterone (DHT) and the ratio of DHT over T in peripheral blood, suppressed the luteinizing hormone concentration, and tended to decrease serum follicle-stimulating hormone concentration. It is concluded that high-dose T undecanoate is not effective in the treatment of men with infertility with idiopathic testicular failure. .A Comhaire F. .I 274984 .U 91006610 .S Fertil Steril 9101; 54(4):694-700 .M Adult; Body Temperature/*; Circadian Rhythm; Diagnosis, Computer-Assisted/*IS; Human; Leg; Male; Monitoring, Physiologic/*IS; Scrotum/BS/*PH; Skin Temperature; Supination; Support, Non-U.S. Gov't; Time Factors; Varicocele/PP. .T A portable digital data recorder for long-term monitoring of scrotal temperatures [see comments] .P JOURNAL ARTICLE. .W The application of a new, miniaturized portable digital data recorder "Thermoport" (Institute for Reproductive Medicine, Munster, West Germany) for continuous determination of scrotal temperatures revealed great variations of scrotal temperature during 24 hours in normal men. Maximum temperatures approached body core temperatures. Mean scrotal temperatures of 10 normal men rose during sauna from 32.72 +/- 0.23 degrees C to 37.53 +/- 0.38 degrees C. During treadmill running, scrotal temperatures increased by more than 2.5 degrees C. Minimal scrotal temperatures were increased in some men with varicocele compared with normal fertile men indicating impaired cooling mechanisms. The continuous temperature measurements facilitate assessment of temperature dynamics. The miniaturized design of the Thermoport makes it suitable for routine use in outpatients of infertility clinics, in occupational medicine for evaluation of heat hazards, and for investigations of body temperatures under various experimental conditions. .A Jockenhovel F; Grawe A; Nieschlag E. .I 274985 .U 91006611 .S Fertil Steril 9101; 54(4):701-7 .M Adult; Animal; Cell Membrane/ME; Female; Hamsters; Human; Infertility, Male/*PP; Luminol/DU; Male; Sperm-Ovum Interactions/*; Spermatozoa/ME/*PH. .T Analysis of sperm function in globozoospermia: implications for the mechanism of sperm-zona interaction. .P JOURNAL ARTICLE. .W The globozoospermic condition has provided a unique opportunity to determine how the abnormal mitochondrial organization and acrosomal loss associated with this syndrome, influence sperm function. Despite the abnormal midpiece architecture, the movement characteristics of the spermatozoa, in terms of the curvilinear, path, and progressive velocities, amplitude of head displacement, and hyperactivation were all within the normal range. Similarly, the behavior of the spermatozoa on Percoll gradients was normal, although the capacity of the isolated fractions to generate reactive oxygen species was negligible. Of particular significance was the fact that the globozoospermic spermatozoa were incapable of sperm-oocyte fusion or binding the human zona pellucida, even after an intracellular calcium signal had been generated with the ionophore A23187. The sudden induction of sperm-zona interaction could, however, be achieved by the use of a ferrous ion promoter system to induce limited lipoperoxidation. This result demonstrates that the enhancing effect of peroxidation on sperm-zona adhesion involves a direct action on the properties of the sperm-plasma membrane, rather than an indirect consequence of acrosomal damage and acrosin leakage. Such findings emphasize the value of specific teratozoospermic conditions, such as globozoospermia, in dissecting the mechanisms that regulate human sperm function. .A Aitken RJ; Kerr L; Bolton V; Hargreave T. .I 274986 .U 91006612 .S Fertil Steril 9101; 54(4):708-12 .M Body Fluids/*PH; Female; Fetal Blood/PH; Graafian Follicle/*ME; Human; Male; Serum Albumin, Bovine/PD; Sex Hormones/PH; Sperm Motility/*; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.. .T Human follicular fluid stimulates hyperactivated motility in human sperm. .P JOURNAL ARTICLE. .W Since human follicular fluid (FF) is known to enhance the acrosome reaction and capacitation, we investigated whether hyperactivated motility is stimulated by FF. Follicular fluid-treated sperm exhibited a threefold increase in hyperactivation compared with the controls. The use of fetal cord serum in the medium, instead of bovine serum albumin, supported the same high levels of hyperactivation, although the peak occurred at 3 hours rather than 5 hours of capacitation. When sperm were treated with a steroid-rich fraction of the FF, hyperactivation was stimulated to the same degree as with whole FF. In contrast, no stimulation occurred when sperm were treated with a FF fraction stripped of steroids. The FF enhancement of hyperactivation in vitro could augment the fertilizing capacity of subfertile sperm samples, providing also a glimpse of possible in vivo events as sperm traverse the FF-laden cumulus oophorus. .A Mbizvo MT; Burkman LJ; Alexander NJ. .I 274987 .U 91006613 .S Fertil Steril 9101; 54(4):713-7 .M Adult; Antitubercular Agents/TU; Egypt; Human; Infertility, Male/*ET/MI/UR; Male; Middle Age; Mycobacterium/IP; Tuberculosis, Urogenital/*CO/DT. .T Genitourinary mycobacteria in infertile Egyptian men. .P JOURNAL ARTICLE. .W Forty infertile patients with a preliminary diagnosis of genitourinary tuberculosis were selected for our study when they presented with one or more of the following: (1) personal or family history of tuberculosis, (2) sterile pyuria, (3) voiding urinary symptoms, (4) abnormality in the epididymis, (5) hemospermia, and (6) clinically unexplained obligoathenospermia. Direct smear examination by Ziehl-Neelsen stain for 24-hour urine and freshly ejaculated semen for 3 days as well as culture of midstream urine and semen were done on egg media. Urine smear was positive (+)ive in 20 patients (50%), culture was (+)ive in 23 (57.5%), whereas for semen smear was (+)ive in 3 (7.3%) and culture was (+)ive in 5 (20%). Tuberculous mycobacteria were detected in 5 of 23 cases (21.7%). Nontuberculous mycobacteria were detected in 18 of 23 cases (78.3%). Mycobacterium smegmatis was the most common mycobacterium isolated. There was improvement of the seminal picture, though not significant, after therapy. .A Abdel Razic MM; el-Morsy FE. .I 274988 .U 91006615 .S Fertil Steril 9101; 54(4):725-9 .M Animal; Emetine/PD; Endometriosis/*CO; Female; Infertility, Female/*ET; Macrophage Activation/*/DE; Macrophages/*TR; Male; Mice; Mice, Inbred BALB C; Peritoneal Cavity/CY; Sperm-Ovum Interactions/*; Support, Non-U.S. Gov't; Transplantation, Heterologous. .T Heterologous transplantation of activated murine peritoneal macrophages inhibits gamete interaction in vivo: a paradigm for endometriosis-associated subfertility. .P JOURNAL ARTICLE. .W Macrophage hyperactivation has been postulated to be the pathologic aberration in patients suffering from endometriosis-associated subfertility. In this report an in vivo model for macrophage-mediated infertility is described. Populations of macrophages were obtained from an inbred strain of mice (Balb/C) as follows: (1) in vivo hyperactivated macrophages (harvested from donor mice treated with intraperitoneal thioglycolate); (2) hyperactivated macrophages deactivated ex vivo with the protein synthesis inhibitor emetine; and (3) basal state (nonactivated) macrophages obtained from untreated mice. Recipient mice underwent ovarian hyperstimulation with pregnant mare serum gonadotropins; 2 x 10(6) macrophages were transferred on the afternoon of stimulation day 3 before injection of human chorionic gonadotropin (hCG) and mating. Unfertilized oocytes and 4-cell embryos were counted on day hCG +2 as a reflection of reproductive performance. Heterologous transfer of in vivo hyperactivated macrophages, but not basal state macrophages, significantly inhibited fertilization. This effect was largely reversed by pretreatment with emetine. These experiments confirm the relevance of macrophage-mediated interference with early reproductive performance and provide a model for the development of alternative therapies (e.g., immunomodulation of the peritoneal fluid environment) for endometriosis-associated subfertility. .A Steinleitner A; Lambert H; Lauredo I. .I 274989 .U 91006616 .S Fertil Steril 9101; 54(4):730-2 .M Adult; Female; Gamete Intrafallopian Transfer/*MT; Human; Male; Pregnancy; Specimen Handling/*; Spermatozoa/*; Time Factors. .T Successful pregnancies resulting from the use of prolonged-incubation human spermatozoa in gamete intrafallopian transfer. .P JOURNAL ARTICLE. .W Human spermatozoa that were incubated overnight at room temperature before intrafallopian transfer with freshly collected oocytes gave rise to successful pregnancies and normal live births. The resulting pregnancy rate per transfer of 50% (4 of 8) compared favorably with the average pregnancy rate of 41.8% (38 of 91), achieved by our standard spermatozoal preparation procedure that prepared the spermatozoa approximately 2 hours before the GIFT operation. This new approach for the preparation of human spermatozoa would be applicable to oligospermic patients and some GIFT patients whose partners may have difficulties in producing a semen specimen immediately before the GIFT operation. .A Chan YM; Chan SY; Tucker MJ; Wong CJ; Leong MK; Leung CK. .I 274990 .U 91006617 .S Fertil Steril 9101; 54(4):733-4 .M Culture Media; Embryo/DE; Embryo Transfer/*MT; Female; Fibrin Tissue Adhesive/*TU; Human; Osmolar Concentration; Pregnancy. .T The use of two-component fibrin sealant for embryo transfer. .P JOURNAL ARTICLE. .W This is a report of our preliminary experience using fibrin sealant with a series of 38 patients undergoing IVF and ET. We used a two-component fibrin sealant to create a fibrin plug in the uterine cavity at the time of ET to decrease the possibility of embryo expulsion and also ectopic pregnancy. Our preliminary report proves that it is possible to obtain 26% pregnancies using this two-component biological glue instead of serum or culture medium for uterine embryo replacement. A prospective randomized study will be undertaken to evaluate whether the use of fibrin sealant could significantly improve IVF and ET results. .A Feichtinger W; Barad D; Feinman M; Barg P. .I 274991 .U 91006618 .S Fertil Steril 9101; 54(4):735-6 .M Adult; Case Report; Embryo Transfer; Female; Fertilization in Vitro/*; Human; Neoplasm Staging; Pregnancy; Pregnancy Complications, Neoplastic/*; Progestational Hormones/*TU; Uterine Neoplasms/*DT/PA. .T Pregnancy after in vitro fertilization in a patient with stage I endometrial carcinoma treated with progestins. .P JOURNAL ARTICLE. .W A 35-year-old woman with chronic anovulation and bilateral tubal disease was found during infertility evaluation to have grade I endometrial carcinoma confined to an endometrial polyp. She was treated with polypectomy and endometrial curettage followed by high-dose progestagens for 6 months. Endometrial curettage at 3 and 6 months of therapy indicated regression of the lesion and the patient subsequently achieved successful pregnancy with IVF. .A Paulson RJ; Sauer MV; Lobo RA. .I 274992 .U 91006620 .S Fertil Steril 9101; 54(4):740-2 .M Adult; Amenorrhea/ET; Bloodletting; Case Report; Female; Gonadorelin/DU; Gonads/PP; Hemochromatosis/*CO/PP/TH; Human; Hypogonadism/*ET; Hypothalamo-Hypophyseal System/PP. .T Secondary hypogonadism in hemochromatosis. .P JOURNAL ARTICLE. .W Hemochromatosis is a rare disorder of iron storage. This report illustrates a case of hypogonadotropic-hypogonadism in a female with biopsy-proven hemochromatosis. Dynamic pituitary and gonadal testing revealed subnormal gonadotropin responses to gonadotropin-releasing hormone (GnRH) but normal ovarian reserve, as shown by normal follicular stimulation with hMG. Thus, abnormalities of ovulation and menstruation in patients with hemochromatosis are most likely because of inadequate pituitary responsiveness to GnRH. .A Meyer WR; Hutchinson-Williams KA; Jones EE; DeCherney AH. .I 274993 .U 91006621 .S Fertil Steril 9101; 54(4):743-4 .M Adhesions/*PC; Clinical Trials; Endometriosis/*DT; Female; Gonadorelin/*AA/TU; Human; Observer Variation; Random Allocation; Statistics/*. .T More on "misuse of statistics" [letter; comment] .P COMMENT; LETTER. .A Adamson GD. .I 274994 .U 91006622 .S Fertil Steril 9101; 54(4):744-6 .M Human; Insemination, Artificial/*; Male; Specimen Handling/*; Sperm Count. .T Semen donor insemination [letter] .P LETTER. .I 274995 .U 91006623 .S Fertil Steril 9101; 54(4):746-7 .M Human; Inflammatory Bowel Diseases/DT; Male; Salicylazosulfapyridine/*AE; Spermatogenesis/*DE. .T Effect of sulfasalazine on spermatogenesis [letter; comment] .P COMMENT; LETTER. .A Riley SA. .I 274996 .U 91006624 .S Fertil Steril 9101; 54(4):748-9 .M Antibodies/*AN; Diagnostic Errors; Female; Human; Infertility/DI; Male; Ovary/*IM; Reagent Kits, Diagnostic/*ST; Spermatozoa/*IM. .T Testing for sperm and ovarian antibodies? [letter] .P LETTER. .A Witkin SS. .I 274997 .U 91006859 .S Diabetes 9101; 39(1):1-5 .M Animal; Diabetes Mellitus, Insulin-Dependent/*DT; Human; Insulin/*PH/TU; Monosaccharide Transport Proteins/PH; Vanadates/TO/*TU. .T Insulin-mimetic effects of vanadate. Possible implications for future treatment of diabetes. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Vanadate ions, low-molecular-weight phosphate analogues, mimic most of the rapid actions of insulin in various cell types. When administered orally to diabetic hyperglycemic rats, vanadate reaches the circulation, mimics insulin stimulation of glucose uptake and metabolism, and leads to normoglycemic and partial anabolic states. In addition, vanadate restores tissue responsiveness to insulin and hepatic glycogen levels and activates new synthesis of key enzymes for carbohydrate metabolism. This suggests that correcting hyperglycemia is sufficient to correct the typical metabolic alterations found in streptozocin-induced diabetic rats. Several weeks of oral administration of vanadate to diabetic rats has not produced detectable liver or kidney toxicity. The mechanism by which vanadate mimics the actions of insulin is still obscure. Unlike insulin, vanadate does not seem to stimulate the autophosphorylation and endogenous tyrosine phosphorylation of insulin-receptor kinase or other intracellular proteins either directly or by virtue of its known inhibitory effect on protein phosphotyrosine phosphatase. Results from many studies support a model in which vanadate activates glucose metabolism by either utilizing an alternative (insulin-independent) cascade or bypassing the early events of the insulin-dependent cascade. Either of these possibilities is of clinical importance, because early insulin events may become defective, as a result of severe hyperinsulinemia, and may contribute to insulin resistance. Alternative pathways by which vanadate may stimulate glucose metabolism, e.g., by increasing intracellular Ca2+ levels and/or regulating intracellular and intravesicular pH, are discussed. From a clinical perspective, studies should be continued in evaluating the level of vanadate toxicity after prolonged treatment and searching for agents that potentiate its insulin mimetic actions in vitro and in vivo. .A Shechter Y. .I 274998 .U 91006860 .S Diabetes 9101; 39(1):104-11 .M Abdomen/PA; Adipose Tissue/*PA; Age Factors; Aged; Asian Americans/GE; Blood Glucose/AN; C-Peptide/*BL; Diabetes Mellitus, Non-Insulin-Dependent/EP/GE/*ME; Fasting/*BL; Follow-Up Studies; Glucose Tolerance Test; Human; Insulin/BL; Japan/EH; Longitudinal Studies; Male; Middle Age; Regression Analysis. .T Association of elevated fasting C-peptide level and increased intra-abdominal fat distribution with development of NIDDM in Japanese-American men. .P JOURNAL ARTICLE. .W The Japanese-American population of King County, Washington, is known to have a high prevalence of non-insulin-dependent diabetes mellitus (NIDDM). As part of a community-based study, we reexamined 146 second-generation Japanese-American men who had been initially classified as nondiabetic. At a mean follow-up period of 30 mo, 15 men had developed NIDDM, and 131 remained nondiabetic. The variables measured at the initial visit that distinguished the 15 diabetic men from the 131 nondiabetic men were older age, higher serum glucose level at 2 h after 75 g oral glucose, higher fasting plasma C-peptide level, and increased cross-sectional intra-abdominal fat area as determined by computed tomography. Both older age and higher 2-h glucose levels are variables that have been associated with the development of NIDDM, but the association of higher fasting C-peptide level and greater intra-abdominal fat area with subsequent development of NIDDM were new observations. The elevated fasting C-peptide level persisted after adjustment for fasting serum glucose. The elevated C-peptide level represents hypersecretion of insulin and was interpreted to reflect a compensatory response to an underlying insulin-resistant state that antedates the development of NIDDM. The fasting C-peptide level was correlated with the intra-abdominal fat area, suggesting that the intra-abdominal fat area may be associated with insulin resistance. Thus, in individuals who develop NIDDM, insulin resistance, increased insulin secretion, and increased intra-abdominal fat are present before diabetic glucose tolerance can be demonstrated. .A Bergstrom RW; Newell-Morris LL; Leonetti DL; Shuman WP; Wahl PW; Fujimoto WY. .I 274999 .U 91006861 .S Diabetes 9101; 39(1):112-7 .M Animal; Cell Separation; Cells, Cultured; Culture Media/AN/PD; Glucose/AD/AN/PD; Insulin/*SE; Islets of Langerhans/CY/*SE; Male; Perfusion; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Pulsatile insulin secretion in isolated rat islets. .P JOURNAL ARTICLE. .W The pancreas secretes insulin in an oscillatory fashion, but the precise site of the pacemaker for pulsatile insulin secretion has not been identified. These studies were designed to determine whether islets also secrete insulin in a pulsatile fashion if they are isolated from their pancreatic milieu. Isolated rat islets (80-100) were perifused 8 h in culture medium after overnight incubation, and samples were collected at 3.3-min intervals. Insulin secretion was evaluated for pulsatility with the Clifton Cycle Detection Program. Perifusion of islets was associated with a spontaneous, persistent, and regular pulsatility of insulin secretion, which was observed in all conditions tested. Perifusion with medium containing 5.5 mM glucose (n = 11) demonstrated oscillations with a mean periodicity of 17.6 +/- 1.1 min and a mean amplitude of 4.8 +/- 0.4 microU/ml when overall mean insulin concentration was 16.7 +/- 2.4 microU/ml. When the glucose concentration was 16.7 mM (n = 9), overall mean insulin concentration was 54.4 +/- 2.6 microU/ml, with increases in periodicity (22.0 +/- 1.3 min) and amplitude (10.7 +/- 0.5 microU/ml). All measurements were significantly different from those observed during perifusion with 5.5 mM glucose (P less than 0.02-0.001). Theophylline (1 mM) also enhanced the overall mean insulin concentration and amplitude (69.4 +/- 10.4 and 14.2 +/- 1.2 microU/ml, respectively) compared with control studies without theophylline (16.7 +/- 5.3 and 4.3 +/- 0.5 microU/ml) (P less than 0.01). The period of the cycle was also increased from 17.5 +/- 1.1 to 26.4 +/- 6.3 min, but this was not significantly different from the control group.(ABSTRACT TRUNCATED AT 250 WORDS) .A Chou HF; Ipp E. .I 275000 .U 91006862 .S Diabetes 9101; 39(1):118-22 .M Amino Acid Sequence; Amino Acids/AN; Amyloid/*CH/GE/ME; Animal; Base Sequence; Cats; DNA/AN/GE; Islets of Langerhans/*CH/ME; Molecular Sequence Data; Polymerase Chain Reaction; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Structure of cat islet amyloid polypeptide and identification of amino acid residues of potential significance for islet amyloid formation. .P JOURNAL ARTICLE. .W Cats and humans, unlike most rodent species, develop amyloid in the islets of Langerhans in conjunction with non-insulin-dependent diabetes mellitus. The amyloid consists of a 37-amino acid polypeptide referred to as islet amyloid polypeptide (IAPP). The primary structures of IAPP from human and three rodent species have previously been determined. Sequence divergence was seen in the region corresponding to amino acid residues 20-29, which in human IAPP has been suggested to confer the amyloidogenic properties to the molecule. Using polymerase chain-reaction methodology, we determined the primary sequence of cat IAPP. Amino acid region 20-29 shows specific similarities and differences compared with human and rodent IAPP, respectively. A synthetic cat IAPP20-29 decapeptide formed amyloid fibrils spontaneously in vitro. Comparison between the structure and amyloid fibril-forming activity of various synthetic peptides suggests that the amino acid residues at positions 25-26 in mature IAPP are important for the amyloidogenic properties of the molecule. .A Betsholtz C; Christmanson L; Engstrom U; Rorsman F; Jordan K; O'Brien TD; Murtaugh M; Johnson KH; Westermark P. .I 275001 .U 91006863 .S Diabetes 9101; 39(1):12-6 .M Allantois/CY/DE; Alloxan; Animal; Aqueous Humor/*PH; Cattle; Cell Division/DE; Cells, Cultured; Chorion/CY/DE; Diabetes Mellitus, Experimental/CO/*PP; Diabetic Retinopathy/ET/PP; Dose-Response Relationship, Drug; Endothelium, Vascular/DE/PA; Eye/*BS/DE; Male; Neovascularization/*PP; Rabbits; Time Factors; Tissue Extracts/PD. .T Absence of angiogenesis-inhibitory activity in aqueous humor of diabetic rabbits. .P JOURNAL ARTICLE. .W We studied inhibitory activity of angiogenesis in the eye to explore the formation of new blood vessels in diabetic microvascular diseases. When we examined the effects of extracts from various ocular tissues of nondiabetic rabbits on the proliferation of bovine aortic endothelial cells, potent inhibitory activity was found in lens and aqueous humor. Aqueous humor inhibited both angiogenesis on chorioallantoic membrane in vivo and promotion of endothelial cell growth in vitro, which were induced by retinal extracts. However, in diabetic rabbits, aqueous humor lost the ability to inhibit the growth of endothelial cells. The loss of activity became evident 1 mo after the alloxan injection and lasted while the animals were hyperglycemic. In addition, diabetic aqueous humor failed to suppress retinal extract-induced angiogenesis promotion and endothelial cell growth. The absence of the inhibitory activity of angiogenesis in diabetic aqueous humor might be involved in promotion of neovascularization in diabetic ocular disease. .A Okamoto T; Oikawa S; Toyota T. .I 275002 .U 91006864 .S Diabetes 9101; 39(1):123-8 .M Amino Acid Sequence; Amino Acids/AN; Base Sequence; DNA/AN/GE; Exons; Gene Amplification; Human; Molecular Sequence Data; Nucleotides/AN; Polymerase Chain Reaction; Receptors, Insulin/AN/*GE; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Human insulin-receptor gene. Partial sequence and amplification of exons by polymerase chain reaction. .P JOURNAL ARTICLE. .W The partial sequence of the human insulin-receptor (hINSR) gene is presented. Using the gene sequence as a guide, we selected pairs of oligonucleotide primers from sites in the introns that flank each exon. These primers allowed each of the 22 exons of the hINSR gene to be amplified in vitro by the polymerase chain reaction. The sequences of the gene and oligonucleotide primers will facilitate studies of genetic variation in the hINSR gene and thereby increase our understanding of the role of this gene in the development of insulin-resistant states and glucose intolerance. .A Seino S; Seino M; Bell GI. .I 275003 .U 91006865 .S Diabetes 9101; 39(1):17-21 .M Allosteric Regulation/PH; Allosteric Site; Chromatography, Ion Exchange; Diphosphoglyceric Acids/*PD; Glucose/ME; Hemoglobin A, Glycosylated/*AN/ME; Hemoglobins/*ME; Human; Oxygen/ME; Phytic Acid/*PD; Polyphosphates/*PD; Support, Non-U.S. Gov't. .T Immediate elimination of labile HbA1c with allosteric effectors of hemoglobin. .P JOURNAL ARTICLE. .W Our aim was to find a simple method of removing labile glycosylated hemoglobin (HbA1c) from blood samples before it is measured by cation-exchange chromatography. Labile HbA1c is formed by the binding of glucose to the NH2-terminal valine of the beta-chain of HbA. We sought a more competitive binder for the same site to dissociate labile HbA1c to glucose and HbA. Inorganic phosphates were found to have a strong allosteric effect and a great ability to eliminate labile HbA1c. We developed our method with 4 mM tetrapolyphosphate in the hemolyzing solution to eliminate labile HbA1c during the automatic processing (at pH 6 and heated for 2 min at 45 degrees C) of blood samples for HbA1c estimation. This may be useful when estimating HbA1c by the manual method. .A Nakashima K; Hattori Y; Yamazaki K; Takechi M; Andoh Y; Miyaji T. .I 275004 .U 91006866 .S Diabetes 9101; 39(1):22-30 .M Adult; Blood Glucose/AN; Calorimetry; Comparative Study; Fatty Acids, Nonesterified/BL/*ME; Glucose/*ME/PK; Glucose Clamp Technique; Human; Hyperglycemia/ME/*PP; Hyperinsulinism/ME/*PP; Insulin/BL/PD; Male; Middle Age; Oxidation-Reduction/DE; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Effect of hyperinsulinemia and hyperglycemia on intracellular glucose and fat metabolism in healthy subjects. .P CLINICAL TRIAL; JOURNAL ARTICLE. .W Hyperinsulinemia and hyperglycemia per se both stimulate glucose uptake and the disposal of glucose by oxidative (Gox) and nonoxidative (Nox) metabolism. However, the intracellular metabolic fate of glucose may not be the same when glucose uptake is stimulated predominantly by either of these mechanisms due to different effects on fat oxidation (Fox). To address this issue, 11 healthy subjects each had four glucose-clamp studies performed in combination with indirect calorimetry to compare Gox, Nox, and Fox at two different rates of glucose uptake (approximately 7 and 10 mg.kg-1 fat-free mass [FFM].min-1) matched at each level by either hyperglycemia or hyperinsulinemia. When glucose uptake was matched at the lower rate (7 mg.kg-1 FFM.min-1), there was less suppression of both FFA (33 vs. 43%, P less than 0.05) and Fox (73 vs. 90%, P less than 0.05) and less stimulation of incremental (above basal) Gox (1.95 vs. 2.49 mg.kg-1 FFM.min-1, P less than 0.025) at low insulin (72 pM) and hyperglycemia (21.8 mM) compared with high insulin (280 pM) and euglycemia (5.1 mM). Matching glucose uptake at the higher rates (10 mg.kg-1 FFM.min-1) required greater than 300 pM of insulin (309 and 632 pM) in both studies and resulted in maximal suppression of FFA (49 vs. 46%, NS) and Fox (both greater than 90%, NS) and similar incremental Gox (2.89 vs. 2.73 mg.kg-1 FFM.min-1, NS) whether at hyperglycemia (15.7 mM) or euglycemia (5.2 mM). Therefore, both hyperinsulinemia and hyperglycemia stimulate glucose uptake and increase intracellular glucose availability, but insulin also regulates Gox by suppression of FFA and Fox. However, when FFA and Fox are maximally suppressed, the rate of glucose uptake, rather than the prevailing insulin level, determines the distribution of intracellular glucose metabolism. .A Thorburn AW; Gumbiner B; Brechtel G; Henry RR. .I 275005 .U 91006867 .S Diabetes 9101; 39(1):31-7 .M Adult; Aged; Aged, 80 and over; Animal; Basement Membrane/CH/ME/UL; Cattle; Cell Fractionation; Collagen/AN/*ME/PH; Diabetes Mellitus/*ME; Electrophoresis, Polyacrylamide Gel; Extracellular Matrix/CH/*ME; Glomerular Mesangium/CH/ME/UL; Human; Immunoblotting; Immunohistochemistry; Kidney Glomerulus/CH/CY/*ME; Lens, Crystalline/CH/CY/ME; Middle Age; Radioimmunoassay; Support, U.S. Gov't, P.H.S.. .T Occurrence of type VI collagen in extracellular matrix of renal glomeruli and its increase in diabetes. .P JOURNAL ARTICLE. .W Human and bovine glomerular basement membrane (GBM) preparations, representing the extracellular matrix of the renal filtration units, were found to contain type VI collagen. This protein was solubilized by guanidine and guanidine-dithiothreitol extractions and characterized after polyacrylamide gel electrophoretic resolution by immunoblotting with an antiserum directed against the alpha 1(VI) and alpha 2(VI) polypeptide chains and by its insensitivity to collagenase digestion in the nonreduced state. In contrast to GBM, which is the product of three distinct cells, type VI collagen could not be detected in extracts from calf lens capsule, an epithelial cell-derived basement membrane. Quantitation by radioimmunoassay of the type VI collagen content of GBM from 17 diabetic and 15 nondiabetic human subjects indicated a 2.8-fold higher level (P less than 0.001) in the diabetic preparations. Because in the glomerulus type VI collagen is considered on the basis of immunohistochemistry to be localized to the mesangium, we believe that measurement of this protein in GBM preparations can provide a valuable index of mesangial expansion in diabetic and other glomerulopathies. .A Mohan PS; Carter WG; Spiro RG. .I 275006 .U 91006868 .S Diabetes 9101; 39(1):38-48 .M Adult; Blood Glucose/AN; Diabetes Mellitus, Insulin-Dependent/DT/*ME; Dose-Response Relationship, Drug; Epinephrine/BL; Female; Glucagon/BL; Glucose/ME; Hemoglobin A, Glycosylated/AN; Human; Hydrocortisone/BL; Insulin/PH/TU; Keto Acids/ME; Leucine/BL/*ME/PH; Male; Norepinephrine/BL; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Leucine metabolism in IDDM. Role of insulin and substrate availability. .P JOURNAL ARTICLE. .W The effect of insulin on plasma amino acid concentrations and leucine metabolism was examined in 18 healthy nondiabetic young volunteers and in 7 subjects with insulin-dependent diabetes mellitus (IDDM) with the euglycemic insulin-clamp technique (40 mU.m-2.min-1) in combination with [1-14C]leucine. All diabetic subjects were studied while in poor metabolic control (fasting glucose 13.3 +/- 1.1 mM; HbA1c 10.8 +/- 0.2%) and again after 2 mo of intensified insulin therapy (fasting glucose 7.2 +/- 0.5 mM; HbA1c 8.0 +/- 0.2%). Insulin-mediated total-body glucose uptake in poorly controlled diabetic subjects (3.6 +/- 0.5 mg.kg-1.min-1) was significantly reduced compared with control subjects (7.5 +/- 0.2 mg.kg-1.min-1; P less than .001) and improved slightly after insulin therapy (4.8 +/- 0.3 mg.kg-1.min-1; P less than .05), although it still remained significantly lower than in control subjects (P less than .01). During the insulin-clamp study performed in subjects with poorly controlled IDDM, endogenous leucine flux (ELF), leucine oxidation (LO), and nonoxidative leucine disposal (NOLD) all decreased (50.1 +/- 2.0 to 26.4 +/- 0.4; 9.2 +/- 0.4 to 6.0 +/- 0.3; 40.9 +/- 2.0 to 20.4 +/- 2.0 mumol.m-2.min-1, respectively) to the same extent as in control subjects. After 2 mo of intensified insulin therapy, the effect of acute hyperinsulinemia on ELF, LO, and NOLD was comparable to that of control subjects, whereas insulin-stimulated glucose metabolism was still impaired. To examine the effect of substrate availability on leucine turnover, well-regulated IDDM and control subjects underwent a repeat insulin-clamp study combined with a balanced amino acid infusion designed to increase circulating plasma amino acid levels approximately twofold. Under these conditions, NOLD was equally enhanced above baseline in both control and IDDM subjects (P less than .01), whereas ELF was inhibited to a greater extent (P less than .01) than during the insulin clamp performed without amino acid infusion (control vs. diabetic subjects, NS). In conclusion, insulin-mediated glucose metabolism is severely impaired in subjects with both poorly controlled and well-controlled IDDM, whereas the effect of acute insulin infusion on leucine turnover is normal, and combined hyperaminoacidemia/hyperinsulinemia stimulated NOLD to a similar extent in both IDDM and control subjects. .A Luzi L; Castellino P; Simonson DC; Petrides AS; DeFronzo RA. .I 275007 .U 91006869 .S Diabetes 9101; 39(1):49-56 .M Chromosome Mapping; Comparative Study; Diabetes Mellitus, Non-Insulin-Dependent/GE; DNA/GE; DNA Restriction Enzymes/GE; Evaluation Studies; Gene Frequency; Genotype; Haplotypes/GE; Human; Linkage (Genetics)/GE; Middle Age; Monosaccharide Transport Proteins/*GE; Negroid Race/GE; Nucleotides/AN; Polymorphism (Genetics)/*GE; Restriction Fragment Length Polymorphisms; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Polymorphisms of HepG2/erythrocyte glucose-transporter gene. Linkage relationships and implications for genetic analysis of NIDDM. .P JOURNAL ARTICLE. .W To assess the contribution of the HepG2/erythrocyte glucose-transporter (HepG2 GT) gene to the inherited susceptibility to non-insulin-dependent diabetes mellitus (NIDDM), cDNA and genomic probes were used to search for restriction-endonuclease polymorphisms at this locus. Analysis of DNA from 16 unrelated Black American individuals with 19 enzymes and as many as six different probes, defined four polymorphisms over a 45-kilobase region. Nucleotide diversity (pi = 0.006) was low relative to that at other loci, with an average of 1 in 1700 base pairs different between two chromosomes at this locus. The observed combined heterozygosity for these four sites was 0.69, which indicates that the markers at this locus could be useful for linkage analysis in families. Linkage-disequilibrium values between the four polymorphisms were evaluated by pairwise analysis and extended haplotypes. Calculating pairwise associations by the disequilibrium statistic delta or by another measure of disequilibrium, D' (the maximum likelihood of disequilibrium, which is less dependent on frequency), significant linkage disequilibrium could not be demonstrated. However, the frequencies of the observed extended haplotypes were shown to differ (chi 2 = 9.1, df = 2, P less than 0.025) from predicted frequencies if the sites were in linkage equilibrium in Blacks. The frequencies of these four polymorphisms were determined in Black nondiabetic (n = 44) and NIDDM (n = 63) subjects. Neither the allelic nor genotypic frequencies of the polymorphisms differed between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) .A Kaku K; Matsutani A; Mueckler M; Permutt MA. .I 275008 .U 91006870 .S Diabetes 9101; 39(1):57-61 .M Animal; Blood Glucose/AN; Collagen/*AN/ME; Comparative Study; Diabetes Mellitus, Experimental/*ME; Glycosylation; Imidazoles/*AN/ME; Male; Rats; Rats, Inbred Strains; Spectrum Analysis, Mass/MT; Support, Non-U.S. Gov't. .T Absence of brown product FFI in nondiabetic and diabetic rat collagen. .P JOURNAL ARTICLE. .W Accumulation of brown products in long-lived proteins might be an important factor in determining long-term diabetic complications. Fluorescent chromophore 2-(2-furoyl)-4-(5)-(2-furanyl)-1H-imidazole (FFI), isolated from hydrolyzed brown products synthesized in vitro, was proposed as a specific brown product responsible for functional and structural changes in long-lived proteins. In this study, an attempt was made to demonstrate by means of collision spectroscopy the presence of FFI in collagen samples taken from diabetic rats. Diabetic rat collagen samples showed mean values of absorbance per milligram of 4-hydroxy-L-proline significantly higher than those observed in nondiabetic rats, suggesting higher FFI levels. Surprisingly, all collagen samples from diabetic and nondiabetic rats gave collision spectra in which no peak diagnostic of FFI presence was observed. These data suggest that the absorbance level observed in diabetic rats is not due to the presence of FFI but to structurally related compounds, which are being investigated by means of mass spectrometry. .A Lapolla A; Gerhardinger C; Pelli B; Sturaro A; Del Favero E; Traldi P; Crepaldi G; Fedele D. .I 275009 .U 91006871 .S Diabetes 9101; 39(1):6-11 .M Diabetes Mellitus, Non-Insulin-Dependent/ET/ME/PP; Glucose/*ME/PH; Homeostasis/PH; Human; Monosaccharide Transport Proteins/*GE/ME/PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Family of glucose-transporter genes. Implications for glucose homeostasis and diabetes. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Glucose transport by facilitated diffusion is mediated by a family of tissue-specific membrane glycoproteins. At least four members of this gene family have been identified by cDNA cloning. The HepG2-type transporter is the most widely distributed of these proteins. It provides many cells with their basal glucose requirement for ATP production and the biosynthesis of sugar-containing macromolecules. The liver-type transporter is expressed in tissues from which a net release of glucose can occur and in beta-cells of pancreatic islets. A genetic defect resulting in reduced activity of this transporter could hypothetically lead to the two principal features of non-insulin-dependent diabetes mellitus, insulin resistance and relative hypoinsulinemia. The adipocyte/muscle transporter is expressed exclusively in tissues that are insulin sensitive with respect to glucose uptake. This protein is an excellent candidate for a highly specific genetic defect predisposing to insulin resistance. .A Mueckler M. .I 275010 .U 91006872 .S Diabetes 9101; 39(1):62-9 .M Adenosine/*PH; Animal; Blood Glucose/AN; Dogs; Dose-Response Relationship, Drug; Female; Glucagon/PD; Insulin/*PD; Liver/*DE/ME/PH; Male; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Adenosine reversal of in vivo hepatic responsiveness to insulin. .P JOURNAL ARTICLE. .W Modulation by adenosine of hepatic responsiveness to insulin was investigated in vivo in 10 healthy mongrel dogs of both sexes by determining net hepatic glucose output (NHGO) in response to insulin during the presence or absence of exogenous adenosine infusion. In addition, two separate series of experiments were performed to study the effect of adenosine (n = 7) or glucagon (n = 5) on NHGO. Basal NHGO, quantitated via the Fick principle, was significantly decreased by insulin infusion (4 U/min; 4.8 +/- 0.6 vs. -1.7 +/- 2.6 mg.kg-1.min-1, P less than 0.05). The addition of an intrahepatic arterial infusion of adenosine (10 mumol/min) during insulin infusion caused glucose output to return to basal levels (insulin, -1.7 +/- 2.6 mg.kg-1.min-1; insulin + adenosine, 3.8 +/- 1.6 mg.kg-1.min-1, P less than 0.05). The addition of intrahepatic arterial saline (control) during insulin infusion had no effect on insulin's action (insulin, -1.0 +/- 1.9 mg.kg-1.min-1; insulin + saline, -1.2 +/- 1.6 mg.kg-1.min-1, P greater than 0.05). Hepatic glucose, lactate, and oxygen deliveries were not affected during either insulin or insulin plus adenosine infusion. Intrahepatic arterial infusion of adenosine alone had no effect on NHGO, whereas intrahepatic arterial infusion of glucagon alone stimulated glucose output approximately fivefold (basal, 2.7 +/- 0.4 mg.kg-1.min-1; glucagon, 15.5 +/- 1.2 mg.kg-1.min-1, P less than 0.01). These results show that adenosine completely reversed the inhibition by insulin of NHGO. These data suggest that adenosine may act as a modulator of insulin action on the liver. .A McLane MP; Black PR; Law WR; Raymond RM. .I 275011 .U 91006873 .S Diabetes 9101; 39(1):70-5 .M Animal; Animals, Newborn/ME; Cell Cycle; Cell Division/PH; Cell Separation; Cells, Cultured; Insulin/SE; Islets of Langerhans/CY/*EN/ME; Pancreas/CY/ME/PH; Rats; Rats, Inbred Strains; Regeneration/PH; Support, Non-U.S. Gov't; Thymidine/DU; Thymidine Kinase/*ME; Tritium/DU. .T Islet cell thymidine kinase activity as indicator of islet cell proliferation in rat pancreas. .P JOURNAL ARTICLE. .W The activity of thymidine kinase (TK;EC 2.7.1.21) in homogenates of isolated rat islets of Langerhans was measured and correlated with the DNA replicatory activity of the islet cells. Adult and fetal rat islets were cultured in medium with 2.7 or 16.7 mM glucose or 16.7 mM glucose and 1 microgram/ml human growth hormone. In both types of islets, 16.7 mM glucose doubled [3H]thymidine incorporation compared with 2.7 mM glucose, and the addition of growth hormone caused a further increase in DNA replication. TK activity in the islets showed similar changes in response to glucose and growth hormone. The correlation between [3H]thymidine incorporation and TK activity was thus highly significant. Cell-cycle analysis of cultured fetal rat islets showed that TK activity was preferentially expressed during the S phase of the cell cycle. TK activity of freshly isolated islets declined with the age of the animal. In pancreatic sections, the islet cell autoradiographic labeling index after [3H]thymidine administration in vivo likewise declined with age and was correlated with the TK activity in freshly isolated islets. It is suggested that measurements of islet TK activity can be used as index of islet cell proliferation; this method has the distinct advantage of avoiding the cumbersome procedure of preparing and scoring autoradiograms. .A Swenne I. .I 275012 .U 91006874 .S Diabetes 9101; 39(1):76-82 .M Adult; Angiotensin-Converting Enzyme Inhibitors/*PD/TU; Biological Transport/DE/PH; Cell Membrane/DE/PH/UL; Cell Membrane Permeability/DE/*PH; Dextrans/PK; Diabetic Nephropathies/DT/*PP; Enalapril/PD/TU; Female; Glomerular Filtration Rate/DE/PH; Human; Kidney Glomerulus/DE/*PP/UL; Male; Middle Age; Oligopeptides/*PD/TU; Proteins/PK; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Effects of converting-enzyme inhibition on barrier function in diabetic glomerulopathy. .P CLINICAL TRIAL; JOURNAL ARTICLE. .W Differential solute clearances were used to examine the effects of a 90-day course of enalapril on glomerular barrier function in 16 proteinuric patients with diabetic glomerulopathy. By day 90, plasma renin and prorenin became elevated, and arterial pressure declined. Transglomerular passage of dextrans of broad size distribution (radii 28-60 A) was lowered significantly. In a subset of 8 patients, withdrawal of enalapril was followed after an additional 30 days by a return of renin levels and arterial pressure to pretreatment levels. The dextran-sieving profile also returned to baseline, becoming uniformly elevated above treated day-90 levels. A theoretical analysis of the serial dextran-sieving profiles indicated that enalapril shifted glomerular pore size distribution to smaller size. These changes in barrier size selectivity were associated with a reduction in fractional albumin and IgG clearances during enalapril therapy and a subsequent rise in these quantities after its withdrawal; urinary protein excretion rate tended to vary in parallel. We conclude that inhibition of converting enzyme in humans with established diabetic glomerulopathy diminishes glomerular permeability to proteins by enhancing barrier size selectivity. Because neither enalapril therapy nor its withdrawal influenced the glomerular filtration or renal plasma flow rates significantly, we propose that the primary action of enalapril may be to modulate the intrinsic membrane properties of the glomerular barrier. .A Morelli E; Loon N; Meyer T; Peters W; Myers BD. .I 275013 .U 91006875 .S Diabetes 9101; 39(1):83-6 .M Animal; Cyclosporins/AE/*PD; Diabetes Mellitus, Experimental/CI/*ME/PP; Disease Models, Animal; Dose-Response Relationship, Drug; Endotoxins/AE/PD; Female; Rats; Rats, Inbred Strains; Shwartzman Phenomenon/*ME/PP; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Thrombosis/CI/ME/PP. .T Effect of cyclosporin on generalized Shwartzman reaction in diabetic rats. .P JOURNAL ARTICLE. .W The effect of cyclosporin (CsA) on the endotoxin-induced generalized Shwartzman reaction (GSR) was studied in diabetic and nondiabetic rats. After 4.5 wk of diabetes, CsA (20 mg/kg) or intralipid as a control substance was given intraperitoneally daily for 10 days. Next, diabetic rats were given either high-dose (2 mg/kg or low-dose (0.1 mg/kg) endotoxin (Escherichia coli 026:B6 lipopolysaccharide B) as a single injection. The rats were killed at intervals of 1, 4, 8, and 24 h. No significant glomerular thrombi were seen in the nondiabetic control animals, whereas the severity of glomerular thrombi in the diabetic animals was dependent on the presence or absence of CsA, endotoxin dose, and degree of glycemic control. In the diabetic rats, glomerular thrombi occurred maximally at 4 h but were no longer present at 24 h. The CsA/high-dose-endotoxin rats had fewer glomerular thrombi than rats receiving the intralipid/high-dose endotoxin, but this difference was not statistically significant. The CsA/low-dose-endotoxin rats had increased glomerular thrombi compared with the intralipid/low-dose-endotoxin rats (P less than 0.01). Insulin treatment reduced the glomerular capillary thrombi in the CsA/low-dose-endotoxin diabetic animals. Thus, CsA aggravates the GSR with low-dose endotoxin but has no significant effect when high-dose endotoxin is given. Improved glycemic control reduces the GSR in CsA-treated rats. Thus, the interrelationships of diabetes, endotoxin, and CsA on the GSR are complex, and the pathogenesis of these events is unclear. .A Bunchman TE; Mauer SM; Kim Y. .I 275014 .U 91006876 .S Diabetes 9101; 39(1):87-95 .M Animal; Blood Glucose/AN; Consciousness/*PH; Dogs; Fasting/ME; Female; Glucagon/BL; Glucose/AD/*ME/PK; Hyperinsulinism/ME; Infusions, Intravenous; Insulin/BL/*ME; Lactates/ME; Liver/DE/*ME/PH; Male; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Interaction between insulin and glucose-delivery route in regulation of net hepatic glucose uptake in conscious dogs. .P JOURNAL ARTICLE. .W In the presence of fixed basal levels of insulin, the route of intravenous glucose delivery (protal vs. peripheral) determines whether net hepatic glucose uptake (NHGU) occurs. Our aims were to determine if the route of intravenous glucose delivery also plays a role in regulating NHGU in the presence of hyperinsulinemia and to determine if length of fast (18 vs. 36 h) influences regulation of NHGU. Five conscious dogs fasted 18 h were given somatostatin and replacement insulin (245 +/- 34 microU.kg-1.min-1) and glucagon (0.65 ng.kg-1.min-1) infusions intraportally. After a 40-min control period, the insulin infusion rate was increased fourfold, and glucose was infused for 3 h. Glucose was given either through a peripheral vein or the portal vein for 90 min to double the glucose load reaching the liver. The order of infusions was randomized. NHGU was measured with the arterial - venous difference technique. Insulin and glucagon levels were 12 +/- 2, 35 +/- 6, and 36 +/- 5 microU/ml and 55 +/- 12, 61 +/- 13, and 59 +/- 7 pg/ml during the control, peripheral, and portal infusions, respectively. The glucose infusion rate, the load of glucose reaching the liver, and the arterial-portal plasma glucose gradient were 0, 9.58 +/- 2.28, and 10.44 +/- 2.94 mg.kg-1.min-1; 29.4 +/- 3.6, 56.8 +/- 3.4, and 56.8 +/- 2.8 mg.kg-1.min-1; and 2 +/- 1, 5 +/- 1, and -51 +/- 15 mg/dl during the same periods.(ABSTRACT TRUNCATED AT 250 WORDS) .A Adkins-Marshall BA; Myers SR; Hendrick GK; Williams PE; Triebwasser K; Floyd B; Cherrington AD. .I 275015 .U 91006877 .S Diabetes 9101; 39(1):96-103 .M Alleles; Amino Acid Sequence; Base Sequence; Chromosome Mapping; Diabetes Mellitus, Insulin-Dependent/*GE; Disease Susceptibility/GE; DNA/*GE; Electrophoresis, Polyacrylamide Gel; Haplotypes/GE; Human; HLA-DQ Antigens/*GE; HLA-DR4 Antigen/GE; Molecular Sequence Data; Polymorphism (Genetics)/*GE; Precipitin Tests. .T HLA-DQ beta sequence polymorphism and genetic susceptibility to IDDM. .P JOURNAL ARTICLE. .W The analysis of HLA-DQ beta nucleotide sequence polymorphism in insulin-dependent diabetes mellitus (IDDM) patients and control subjects suggests a role for the DQ beta-chain in genetic susceptibility. Sequence determination and oligonucleotide hybridization was carried out on enzymatically amplified DNA from various HLA-DR-typed individuals, including the rare class of DR2+ patients. In the analysis of DQ beta variation in DR4, DRw6, and DR2 haplotypes, a correlation was observed between the presence of the negatively charged residue Asp at position 57 and low susceptibility and the presence of an Ala (DR4), Val (DRw6), or Ser (DR2) and higher susceptibility. However, important exceptions to this pattern have been identified in the analysis of heterozygous DR1/4 IDDM patients. In these individuals, susceptibility appears to correlate with specific DR beta l alleles (Dw4) on the DR4 haplotype, rather than with the DQ beta allele (DQB3.2) that contains Ala at position 57. The DQ beta alleles found in some Chinese IDDM patients also proved discordant with the position-57 correlations. Thus, although there is a general correlation between the residue at position 57 of the DQ beta-chain and IDDM susceptibility, these data do not support the notion that Asp 57 confers complete resistance or protection to IDDM. In general, these results suggest that IDDM susceptibility is conferred by specific combinations of DQ beta and DR beta sequences. .A Erlich HA; Bugawan TL; Scharf S; Nepom GT; Tait B; Griffith RL. .I 275016 .U 91006878 .S Diabetes 9101; 39(10):1153-7 .M Diabetes Mellitus, Insulin-Dependent/GE/*IM; Disease Susceptibility; Human; HLA Antigens/*GE; Immunity, Natural; Major Histocompatibility Complex/*; Models, Genetic; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T A unified hypothesis for the complex genetics of HLA associations with IDDM. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Our understanding of the role of HLA genes associated with insulin-dependent diabetes mellitus (IDDM) is in disarray, despite recent improvements in the definition of specific alleles and haplotypes. Some genes are highly associated with IDDM, other genes are associated with resistance to IDDM, and some highly associated susceptibility genes are markedly influenced by trans-associated synergistic effects (DR3/4 heterozygotes) or protective effects (DR2/4 heterozygotes). This plethora of genetic associations has spawned the notion that there are many contributing susceptibility genes, which, in turn, has led to the search for shared structural features among different genes on IDDM-associated haplotypes. From a more mechanistic point of view, however, the wide range of variable IDDM associations, with both cis- and trans-encoded protective and/or synergistic effects, suggests a different approach. This article proposes a hypothesis in which the different HLA associations with IDDM can be simply explained by a single unifying concept: a hierarchy of affinities determines the interaction between a diabetogenic peptide and different class II molecules, and an individual is susceptible to IDDM if the class II molecule in that individual with the highest affinity for such a peptide is a DQ beta susceptibility gene. The explicit formulation of this proposal and its genetic implications provide an explanation for HLA-encoded dominant "protection" and for some of the more subtle genetic observations related to cis and trans influences in IDDM susceptibility. .A Nepom GT. .I 275017 .U 91006879 .S Diabetes 9101; 39(10):1158-64 .M Adult; Apolipoproteins/BL; Cholesterol/BL; Diabetes Mellitus, Insulin-Dependent/*BL; Human; Lipoproteins/*BL; Male; Reference Values; Support, Non-U.S. Gov't; Triglycerides/BL. .T Differences in lipoprotein subfraction composition and distribution between type I diabetic men and control subjects. .P JOURNAL ARTICLE. .W Subfractions of very-low-density and low-density lipoproteins were examined in 10 male normolipidemic type I (insulin-dependent) diabetic patients before and after improvement of metabolic control and were compared with subfractions from male control subjects matched to the diabetic patients at entry for age, body mass index, plasma cholesterol, and plasma triglycerides. Two consistent differences in subfraction composition were noted between the diabetic patients at entry and the control subjects. First, subfractions from diabetic patients tended to be cholesterol-ester poor and triglyceride rich; this was particularly marked for the low-density lipoprotein subfractions. Second, the subfractions from pretreatment diabetic patients contained higher proportions of non-apolipoprotein B apolipoproteins. This compositional anomaly, but not the lipid modifications, responded to but was not completely normalized by improved glycemic control, which was also accompanied by reductions in the plasma concentrations of all subfractions. Treatment modified subfraction distribution so that the lipoprotein profile of posttreatment diabetic patients more closely resembled the profile observed in the control subjects. These changes were achieved without significant modification of daily insulin dose. In the context of blood lipid risk factors, the results argue for the need to maintain optimal insulinization even in apparently normolipidemic diabetic patients to avoid modifications of the lipoprotein pattern toward a potentially more atherogenic profile. .A James RW; Pometta D. .I 275018 .U 91006880 .S Diabetes 9101; 39(10):1165-9 .M Adult; Animal; Autoantibodies/*; Diabetes Mellitus, Insulin-Dependent/*IM; Female; Glucose/PD; Human; In Vitro; Insulin/SE; Islets of Langerhans/*IM/ME/SE; Male; Proinsulin/*GE; Protein Precursors/*GE; Rats; Rats, Inbred Strains; RNA, Messenger/DE/*GE/IP; Support, Non-U.S. Gov't. .T Increased preproinsulin mRNA in pancreatic islets incubated with islet cell-stimulating antibodies from serums of type I diabetic patients. .P JOURNAL ARTICLE. .W We recently described autoantibodies that stimulate the release of insulin from pancreatic beta-cells both in vitro and in vivo. The aim of this study was to establish whether islet cell-stimulating antibodies (ICSTAs) also increase islet cell preproinsulin mRNA content. Wistar rat islets, isolated by collagenase digestion, were exposed to 2.7 and 11.1 mM glucose. Insulin release increased 10-fold in response to the higher glucose concentration, and dot-blot analysis of islet mRNA with a rat preproinsulin cDNA probe showed a concomitant increase in mRNA levels. The globulin fractions of four test serums, three from patients with type I (insulin-dependent) diabetes and one from a patient with the insulin autoimmune syndrome, showed clear (5- to 8-fold) stimulation of insulin release. The nonglobulin fractions of these serums and both fractions of three control serums failed to stimulate secretion of insulin. The insulin mRNA content of islets incubated with the ICSTA globulin fractions was greatly increased compared with levels observed in islets treated with control serum globulin fractions. We conclude that ICSTAs not only can stimulate the release of insulin but also increase the preproinsulin mRNA content of islet cells. .A Foggensteiner L; Bone AJ; Webster KA; Wilkin TJ. .I 275019 .U 91006881 .S Diabetes 9101; 39(10):1170-6 .M Animal; Cyclohexanones/*PD; Glucokinase/*AI; Hexokinase/ME; In Vitro; Islets of Langerhans/DE/EN/*SE; Kinetics; Liver/EN; Male; Monosaccharides/PD; Rats; Rats, Inbred Strains. .T Participation of glucokinase inactivation in inhibition of glucose-induced insulin secretion by 2-cyclohexen-1-one. .P JOURNAL ARTICLE. .W We assessed our speculation that 2-cyclohexen-1-one (CHX) impairs glucose-induced insulin secretion through inactivation of glucokinase. Treatment of pancreatic islets with CHX at concentrations (0-5 mM) that caused a dose-dependent inactivation of glucokinase activity similarly inhibited glucose-induced insulin secretion. Another glucose-phosphorylating enzyme (hexokinase) in pancreatic islets was little affected by CHX. CHX-induced inactivation of glucokinase was blocked by the presence of its substrates (glucose and mannose) and an inhibitor (N-acetylglucosamine), all of which also protected against the inhibitory effect of the drug on glucose-induced insulin secretion. CHX also impaired insulin secretion induced by D-glyceraldehyde and dimethyl succinate, which are believed to stimulate the release of the hormone by being directly oxidized by glyceraldehyde-3-phosphate dehydrogenase, by entering the midstream of the glycolytic pathway as glyceraldehyde 3-phosphate, or by entering the tricarboxylic acid cycle in mitochondria after intracellular hydrolysis. The inhibitory effect of CHX on glucose-induced insulin secretion, however, was far more marked than that on insulin secretion evoked by D-glyceraldehyde and dimethyl succinate at any CHX concentrations used. Our study revealed that the inhibitory action of CHX on glucose-induced insulin secretion is exerted mainly, but not solely, through inactivation of glucokinase. This conclusion supports the view that glucokinase is a key enzyme in the recognition of glucose as an insulin secretagogue in pancreatic islets. .A Miwa I; Murata T; Mitsuyama S; Okuda J. .I 275020 .U 91006882 .S Diabetes 9101; 39(10):1177-81 .M Circadian Rhythm; Diabetes Mellitus, Insulin-Dependent/*PP; Diabetic Neuropathies/*PP; Heart Rate/*; Human; Middle Age; Posture; Reference Values; Respiration; Support, Non-U.S. Gov't; Vagus Nerve/PP; Valsalva's Maneuver. .T Heart-rate variability and cardiac autonomic function in diabetes. .P JOURNAL ARTICLE. .W Cardiac autonomic function was measured in 25 subjects with insulin-dependent diabetes mellitus and 11 control subjects. Autonomic integrity was assessed with standard tests of autonomic function and a new technique of measuring heart-rate variability (HRV) for 24 h. All of the diabetic subjects were selected on the basis of peripheral or autonomic neuropathy or long-term poorly controlled diabetes. They were divided into groups according to presence or absence of vagal neuropathy based on the results of standard tests of autonomic function. Thirteen diabetic subjects had normal autonomic function tests (group 1), and vagal neuropathy was detected in 12 diabetic subjects (group 2). All subjects were monitored by ambulatory electrocardiograph, and the recordings were played back through an analyzer that identified and timed successive pulse (R-R) intervals. HRV was measured from the standard deviation of the successive differences between R-R intervals. HRV was significantly reduced in group 1 (mean +/- SE 73 +/- 9 ms) and group 2 (65 +/- 12 ms) diabetic subjects compared with the control group (138 +/- 10 ms). The standard tests of autonomic function did not distinguish the vagal dysfunction noted with HRV monitoring in group 1 diabetic subjects compared with control subjects. Measurement of 24-h HRV can detect small changes in cardiac autonomic function compared with currently available tests. .A Malpas SC; Maling TJ. .I 275021 .U 91006884 .S Diabetes 9101; 39(10):1191-7 .M Animal; Blood Glucose/*ME; Erythrocytes/*ME; Female; Fetus/*ME; Gestational Age; Glucose/ME; Glycogen/BL; In Vitro; Liver/EM/ME; Liver Glycogen/ME; Pregnancy; Rats; Rats, Inbred Strains. .T Compensation by fetal erythrocytes of plasma glucose changes in rats. .P JOURNAL ARTICLE. .W Changes in plasma glucose and glucose and glycogen content in fetal erythrocytes (FRBCs) were studied in rats between days 15 and 21 of gestation and in adult rats. Plasma and FRBC glucose concentrations increased during fetal life and were higher in erythrocytes than in plasma. Glycogen was higher in FRBCs than in adult erythrocytes and tended to decrease from day 15 to 19 of gestation and to increase again on day 21. When FRBCs were incubated in vitro in different glucose concentrations to study their capacity to compensate for changes in plasma glucose concentration, younger cells showed better glucose-buffering capacities. Glucose and glycogen levels in FRBCs increased when they were incubated in high-glucose medium, and the glycogen concentration reached was higher in the early fetal stage than by the end of gestation. Nevertheless, adult erythrocytes accumulated more glycogen in high-glucose medium than cells from any of the fetal-aged erythrocytes. When glucose was injected intraperitoneally into fetuses of different ages, there was an increase of 3.7 microM/ml in glucose concentration in blood from the umbilical artery and 2.5 microM/ml in blood from the umbilical vein. FRBCs buffered some of this change, as evident by an increase in glycogen content. Again, buffering capacity was greater for erythrocytes in younger fetuses. Epinephrine diminished glycogen concentration in venous FRBCs on days 19 and 21 of gestation even in hyperglycemia. Insulin diminished glucose concentration in arterial plasma on days 17 and 21 of gestation, but there were no changes in glucose and glycogen in FRBCs.(ABSTRACT TRUNCATED AT 250 WORDS) .A Guarner V; Alvarez-Buylla R. .I 275022 .U 91006885 .S Diabetes 9101; 39(10):1198-202 .M Blood Glucose/ME; Diabetes Mellitus, Non-Insulin-Dependent/*BL; Eating; Fasting; Human; Insulin/BL; Male; Middle Age; Reference Values; Somatostatin/*BL; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Fasting and postprandial concentrations of somatostatin-28 and somatostatin-14 in type II diabetes in men. .P JOURNAL ARTICLE. .W Recent evidence suggests that somatostatin-28 (SRIF-28), cleaved from prosomatostatin by cells of the upper intestine, acts as a nutrient-stimulated inhibitor of insulin secretion in healthy men. A role for SRIF-28 in the pathophysiology of diabetes has not been previously explored, although several groups have measured circulating somatostatinlike immunoreactivity (SLI) in diabetic subjects. To investigate the possible mediation of abnormal insulin secretion in diabetes by SRIF-28, plasma levels were measured in 10 non-insulin-dependent diabetic men and 9 age- and weight-matched control subjects. Concentrations of SRIF-14 and SLI were also obtained. Subjects were admitted for study after an overnight fast, blood was collected before and at 30-min intervals for 4 h after a fat meal, and plasma samples were analyzed for SRIF-28 and SRIF-14 by specific methods. Basal glucose levels in the diabetic men were significantly higher than in control subjects (10.2 +/- 1 vs. 5.8 +/- 0.2 mM), but insulin levels were similar (79 +/- 14.2 vs. 93.3 +/- 14.2 pM). The diabetic men had significantly lower basal SRIF-28 levels than the control subjects (11.4 +/- 0.6 vs. 14.6 +/- 1.0 pM, P = 0.017). After fat intake, SRIF-28 levels throughout the 4 h of study were indistinguishable in the two groups (270 vs. 292% of basal). Basal SRIF-14 and SLI levels were not significantly different in the two groups, and SRIF-14 and SLI concentrations rose similarly after the meal. There were no correlations between basal SRIF-28 and glucose or insulin levels.(ABSTRACT TRUNCATED AT 250 WORDS) .A D'Alessio DA; Ensinck JW. .I 275023 .U 91006886 .S Diabetes 9101; 39(10):1203-11 .M Adolescence; Adult; Animal; Antibodies, Monoclonal/*IM; Antigen-Antibody Reactions; Antigenic Determinants/AN; Autoantibodies/*IM; Child; Diabetes Mellitus, Insulin-Dependent/BL/*IM; Diabetes Mellitus, Non-Insulin-Dependent/IM; Human; Insulinoma/*IM; Islets of Langerhans/*IM; Mice; Pancreatic Neoplasms/*IM; Rats; Reference Values; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Strong association between diabetes and displacement of mouse anti-rat insulinoma cell monoclonal antibody by human serum in vitro. .P JOURNAL ARTICLE. .W In an attempt to identify novel pancreatic beta-cell surface antigens, mouse monoclonal antibodies (MoAbs) were raised against rat insulinoma (RIN5F) cells with standard techniques. Several clones were identified whose antibodies bound specifically to RIN5F cells but not to other rat, mouse, and human target cells. Each of these MoAbs was radiolabeled, and the specificity of binding of each MoAb was determined by the ability of excess cold homologous MoAb to displace the labeled MoAb. Six RIN5F cell-specific MoAbs of different epitopic specificities were identified. The relevance of these beta-cell epitopes to human insulin-dependent diabetes (IDDM) was demonstrated by the differential ability of human serums from control and diabetic children to displace the radiolabeled MoAbs from the RIN5F cells. Serums from 333 children without diabetes or a family history of diabetes and from 156 newly diagnosed IDDM patients were tested. Only one IgM MoAb was specifically displaced by the IDDM serums, i.e., 146 of 156, compared to serums from control children, i.e., 10 of 333. With immunofluorescence, the serum component responsible for the displacement of the mouse MoAb was identified as IgG. Most of the positive control serums were from children with active autoimmune thyroiditis. Serums from children with other forms of glucose intolerance did not displace MoAb 1A2. There was no correlation between age and the degree of displacement of 1A2. Thus, the displacement of 1A2 is a specific and sensitive marker of diabetes susceptibility easily applicable to mass screening.(ABSTRACT TRUNCATED AT 250 WORDS) .A Thomas NM; Ginsberg-Fellner F; McEvoy RC. .I 275024 .U 91006887 .S Diabetes 9101; 39(10):1212-7 .M Adult; Blood Proteins/ME; Capillary Permeability/*DE; Glucose Clamp Technique; Human; Hyperinsulinism/PP; Insulin/*PD; Insulin Infusion Systems; Male; Potassium/BL; Reference Values; Serum Albumin/*ME; Sodium/BL; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Increased transcapillary escape rate of albumin in nondiabetic men in response to hyperinsulinemia. .P JOURNAL ARTICLE. .W Diabetic patients manifest increased vascular permeability. To determine whether insulin per se might increase vascular permeability, five nondiabetic men were studied by the hyperinsulinemic-euglycemic clamp technique. Each subject received a 0.72-nmol/kg body wt i.v. insulin bolus, followed by a 72-pmol.kg-1.min-1 insulin infusion for 4 h. Euglycemia was maintained by the Biostator glucose controller. At 7 h of study, 10 microCi i.v. 125I-labeled albumin was injected as bolus dose. Frequent blood samples were drawn during the next 70 min for determination of the transcapillary escape rate (TER) of albumin. Subjects returned 1-2 wk later for a control study, during which 0.45% saline was infused at a rate identical to the dextrose and insulin infusion rates during the hyperinsulinemic clamp. The mean +/- SE serum insulin levels during the hyperinsulinemic clamp and saline infusion were 9786 +/- 126 and 46 +/- 4 pM, respectively, whereas serum glucose during the two sessions was similar (5.0 +/- 0.2 vs. 4.8 +/- 0.1 mM, NS). Identical fluid volumes were infused during the two sessions (1767 +/- 197 ml/7 h), and urine outputs did not differ significantly (1615 +/- 309 vs. 1035 +/- 248 ml/7 h). The TER of albumin was greater in all five men after hyperinsulinemia than after saline infusion (18.3 +/- 2.7 vs. -2.8 +/- 2.3%/h, P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) .A Nestler JE; Barlascini CO; Tetrault GA; Fratkin MJ; Clore JN; Blackard WG. .I 275025 .U 91006888 .S Diabetes 9101; 39(10):1218-27 .M Animal; Benzopyrans/*PD; Blood Glucose/*ME; Cholesterol/BL; Fatty Acids, Nonesterified/BL; Glucagon/BL; Glycerin/BL; Hydroxybutyrates/BL; Hyperglycemia/*BL; Hyperinsulinism/*BL; Hypoglycemic Agents/*PD; Insulin/*BL/PD; Kinetics; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Reference Values; Thiazoles/*PD; Triglycerides/BL. .T Actions of novel antidiabetic agent englitazone in hyperglycemic hyperinsulinemic ob/ob mice. .P JOURNAL ARTICLE. .W The effects of CP 68722 (racemic englitazone) were examined in ob/ob mice, in adipocytes and soleus muscles from ob/ob mice, and in 3T3-L1 adipocytes. Administration of englitazone at 5-50 mg.kg-1.day-1 lowered plasma glucose and insulin dose dependently without producing frank hypoglycemia in either the diabetic or nondiabetic lean animals. The glucose-lowering effect in ob/ob mice preceded the reduction in hyperinsulinemia. On cessation of drug, plasma insulin returned to untreated levels within 48 h, whereas plasma glucose rose slowly over 5 days. Englitazone (50 mg/kg) for 11 days lowered plasma glucose (22.2 +/- 1.4 to 14.0 +/- 1.9 mM), insulin (7.57 +/- 0.67 to 1.64 +/- 0.60 nM), nonesterified fatty acids (1813 +/- 86 to 914 +/- 88 microM), glycerol (9.20 +/- 0.98 to 4.94 +/- 0.03 mM), triglycerides (1.99 +/- 0.25 to 1.03 +/- 0.11 g/L), and cholesterol (6.27 +/- 0.96 to 3.87 +/- 0.57 mM), but no effects were observed 3 h after a single dose. Basal and insulin-stimulated lipogenesis were enhanced in adipocytes from ob/ob mice treated with 50 mg/kg englitazone for 11 days compared with lipogenesis in cells from vehicle-treated controls. Treatment of ob/ob mice with 50 mg/kg englitazone reversed the defects in insulin-stimulated glycolysis (from [3-3H]glucose) and glycogenesis and basal glucose oxidation (from [1-14C]glucose) in isolated soleus muscles. Englitazone (30 microM) stimulated 2-deoxy-D-glucose transport in 3T3-L1 adipocytes from 0.37 +/- 0.03 to 0.65 +/- 0.06 and 1.53 nmol.min-1.mg-1 protein at 24 and 48 h, respectively. Thus, englitazone has 1) insulinomimetic and insulin-enhancing actions in vitro and 2) glucose-, insulin-, triglyceride-, and cholesterol-lowering properties in an animal model of non-insulin-dependent diabetes mellitus (NIDDM) in which sulfonylureas have little or no effect. Thus, this new agent may have beneficial effects including a reduced risk of hypoglycemia in patients with NIDDM. .A Stevenson RW; Hutson NJ; Krupp MN; Volkmann RA; Holland GF; Eggler JF; Clark DA; McPherson RK; Hall KL; Danbury BH; et al. .I 275026 .U 91006889 .S Diabetes 9101; 39(10):1228-34 .M Animal; Biological Transport, Active; Carbon Radioisotopes; Cell Line; Fibroblasts/ME; Glucose/*ME; Kinetics; Methylglucosides/ME; Mice; Radioisotope Dilution Technique; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tritium. .T Evidence that downregulation of hexose transport limits intracellular glucose in 3T3-L1 fibroblasts. .P JOURNAL ARTICLE. .W Measurements of initial glucose entry rate and intracellular glucose concentration in cultured cells are difficult because of rapid transport relative to intracellular volume and a substantial extracellular space from which glucose cannot be completely removed by quick exchanges of medium. In 3T3-L1 cells, we obtained good estimates of initial entry of [14C]methylglucose and D-[14C]glucose with 1) L-[3H]glucose as an extracellular marker together with the [14C]glucose or [14C]methylglucose in the substrate mixture, 2) sampling times as short as 2 s, 3) ice-cold phloretin-containing medium to stop uptake and rinse away the extracellular label, and 4) nonlinear regression of time courses. Methylglucose equilibrated in two phases--the first with a half-time of 1.7 s and the second with a half-time of 23 s; it eventually equilibrated in an intracellular space of 8 microliters/mg protein. Entry of glucose remained almost linear for 10 s, making its transport kinetics easier to study (Km = 5.7 mM, Vmax = 590 nmol.s-1.ml-1 cell water). Steady-state intracellular glucose concentration was 75-90% of extracellular glucose concentration. Cells grown in a high-glucose medium (24 mM) exhibited a 67% reduction of glucose-transport activity and a 50% reduction of steady-state ratio of intracellular glucose to extracellular glucose. .A Whitesell RR; Regen DM; Pelletier D; Abumrad NA. .I 275027 .U 91006890 .S Diabetes 9101; 39(10):1235-42 .M Adult; Blood Glucose/ME; C-Peptide/BL/*SE; Diabetes Mellitus, Insulin-Dependent/BL/*SU; Female; Glucagon/DU; Human; Insulin/BL/*SE; Islets of Langerhans/*SE; Kidney Transplantation/PH; Male; Middle Age; Pancreas Transplantation/MT/*PH; Reference Values; Support, U.S. Gov't, P.H.S.; Transplantation, Homologous. .T Physiological and pharmacological stimulation of pancreatic islet hormone secretion in type I diabetic pancreas allograft recipients. .P JOURNAL ARTICLE. .W Successful heterotopic and denervated pancreas allograft transplantation (PAT) often results in normoglycemia and peripheral hyperinsulinemia in insulin-dependent (type I) diabetic recipients. The contribution of altered hepatic insulin extraction (HIE) to the resulting hyperinsulinemia in such patients remains uncertain. Furthermore, whether the denervated pancreas allografts exhibit beta-cell hyperresponsiveness to physiological and pharmacological stimulation is controversial. We evaluated beta-cell function and HIE after successful whole cadaveric PAT with systemic venous drainage in 13 type I diabetic patients before and after mixed-meal and intravenous glucose and glucagon administration. The results were compared with those of 5 nondiabetic patients with kidney transplantation only, who had native innervated pancreases with portal insulin delivery and were receiving an equivalent triple immunosuppressive therapy (cyclosporin, azathioprine, and prednisone), and 7 healthy control subjects with no family history of diabetes. After PAT, fasting and poststimulation serum glucose concentrations were normalized. PAT was associated with marked basal hyperinsulinemia (3- to 8-fold) as assessed by immunoreactive insulin (IRI) levels in type I diabetic patients (mean +/- SE 345 +/- 43 pM) compared with control subjects (43 +/- 14 pM) and nondiabetic kidney-transplantation patients (129 +/- 38 pM). After mixed-meal ingestion, the mean incremental integrated insulin area was similar in PAT patients (18 +/- 3 nM.min) compared with kidney-transplantation patients (20 +/- 4 nM.min) and healthy control subjects (21 +/- 3 nM.min). Basal serum C-peptide levels were significantly greater in PAT (1.72 +/- 0.13 nM) and kidney-transplantation (2.15 +/- 0.33 nM) patients than in healthy control subjects (0.50 +/- 0.10 nM; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) .A Osei K; Henry ML; O'Dorisio TM; Tesi RJ; Sommer BG; Ferguson RM. .I 275028 .U 91006891 .S Diabetes 9101; 39(10):1243-50 .M Animal; Blood Glucose/ME; Diabetes Mellitus, Experimental/BL/DT/*ME; Fatty Acids, Nonesterified/BL; Glucose/ME; Glycogen/ME; Glycolysis/DE; Insulin/*/BL/PD/TU; Lactates/BL; Lithium/*PD/TU; Male; Muscles/DE/ME; Pancreatectomy; Rats; Rats, Inbred Strains; Reference Values; Support, Non-U.S. Gov't; Vanadates/*PD/TU. .T Insulinomimetic properties of trace elements and characterization of their in vivo mode of action. .P JOURNAL ARTICLE. .W Lithium and vanadate have insulinomimetic actions in vitro. In this study, we examined the in vivo effects of lithium and vanadate on glucose metabolism in diabetic (90% partial pancreatectomy) rats. Four groups of chronically catheterized rats were studied: control, diabetic, diabetic treated with lithium (plasma concn 1.0 +/- 0.1 meq/L) and vanadate (0.05 mg/ml in drinking water), and diabetic treated with lithium, vanadate, zinc, and magnesium. Postmeal plasma glucose was increased in diabetic versus control rats (18.7 vs. 7.7 mM, P less than 0.01) and was normalized by addition of lithium and vanadate (8 mM) or lithium, vanadate, zinc, and magnesium (7.4 mM). Euglycemic insulin-clamp studies were performed 2 wk posttreatment; insulin-mediated glucose uptake was reduced in diabetic compared with control rats (142 +/- 4 vs. 200 +/- 5 mumol.kg-1.min-1, P less than 0.01), returned to normal with lithium and vanadate (206 +/- 6 mumol.kg-1.min-1), or increased to supranormal levels with lithium, vanadate, zinc, and magnesium (238 +/- 6 mumol.kg-1.min-1). During the insulin clamp, muscle glycogenic rate was severely impaired in diabetic versus control rats (18 vs. 70 mumol.kg-1.min-1) and was normalized by lithium and vanadate (91 mumol.kg-1.min-1) or lithium, vanadate, zinc, and magnesium (93 mumol.kg-1.min-1).(ABSTRACT TRUNCATED AT 250 WORDS) .A Rossetti L; Giaccari A; Klein-Robbenhaar E; Vogel LR. .I 275029 .U 91006892 .S Diabetes 9101; 39(10):1251-6 .M Adult; Blood Glucose/ME; Carrier Proteins/*ME; Eating; Fasting; Female; Human; Insulin/BL; Kinetics; Male; Recombinant Proteins/PD; Reference Values; Somatomedins/ME; Somatotropin/BL/*PD; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Time Factors. .T Lack of growth hormone effect on insulin-associated suppression of insulinlike growth factor binding protein 1 in humans. .P JOURNAL ARTICLE. .W Insulinlike growth factor binding protein 1 (IGFBP-1) has been shown to modulate the metabolic and mitogenic actions of the growth hormone (GH)-dependent peptide insulinlike growth factor I. Previous studies showed that levels of IGFBP-1 are regulated by insulin. The relative role of GH in the regulation of IGFBP-1 levels is less well defined and was examined in our study with a contiguous two-part protocol. Overnight (part A) and pre- and post-morning meal (part B) blood samples were obtained from eight healthy adults during a constant infusion of saline (SAL) or 4 micrograms.kg-1.min-1 GH. Five of eight subjects were restudied with glucose (GLUC) infused during part B (SAL + GLUC) to match glucose and insulin to levels observed during GH infusion. During SAL infusion, IGFBP-1 levels measured by specific radioimmunoassay showed a marked immediate decline after the evening meal in part A, with a subsequent nocturnal rise of 2.4- to 17.3-fold. GH infusion resulted in a similar meal-induced fall in IGFBP-1 levels but led to a delayed nocturnal rise in IGFBP-1, which was associated with elevated postprandial insulin concentrations. During part B, changes in plasma IGFBP-1 levels showed a similar pattern, with a delayed postprandial increase observed during both GH and SAL + GLUC infusions. The half-life of IGFBP-1 disappearance was calculated at approximately 2 h for all three infusion groups. Comparison of venous and arterialized blood samples showed no consistent pattern of difference, arguing against peripheral tissue clearance or compartmentalization as the mechanism for the rapid rise and fall in IGFBP-1 levels.(ABSTRACT TRUNCATED AT 250 WORDS) .A Conover CA; Butler PC; Wang M; Rizza RA; Lee PD. .I 275030 .U 91006893 .S Diabetes 9101; 39(10):1257-63 .M Animal; Cattle; Cells, Cultured; Endothelium, Vascular/ME; Fibroblasts/ME; Glucose/PD; Glycosylation; Human; Kinetics; Lipoproteins, HDL/*ME; Macrophages/*ME; Mice; Receptors, Endogenous Substances/DE/*ME; Reference Values; Skin/*ME; Sucrose/PD; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Nonenzymatic glycosylation of HDL resulting in inhibition of high-affinity binding to cultured human fibroblasts. .P JOURNAL ARTICLE. .W Nonenzymatic glycosylation of plasma proteins may contribute to the excess risk of developing atherosclerosis in patients with diabetes mellitus. Because high-density lipoprotein (HDL) is believed to protect against atherosclerosis and is glycosylated at increased levels in diabetic individuals, the effects of nonenzymatic glycosylation of HDL3 on binding of HDL3 to cultured fibroblasts and to the candidate HDL-receptor protein were examined. HDL3 was glycosylated in vitro with glucose alone or in combination with sodium cyanoborohydride. With this catalyst, up to 40-50% of the lysine residues could be glycosylated, resulting in a progressive drop to nearly 60% in high-affinity binding to cultured fibroblasts at 4 degrees C. Binding to the 110,000-Mr candidate HDL-receptor protein was reduced by almost 75%. At levels of HDL glycosylation equivalent to the 3-5% observed in diabetes, high-affinity binding to fibroblasts at 4 degrees C was diminished by up to 15-20%. Binding kinetic studies paradoxically suggested that glycosylated HDL3 binds with higher affinity to a reduced number of binding sites. The findings in this study suggest that nonenzymatically glycosylated HDL may be functionally abnormal and might contribute to the development of atherosclerosis in patients with diabetes mellitus. .A Duell PB; Oram JF; Bierman EL. .I 275031 .U 91006894 .S Diabetes 9101; 39(10):1264-72 .M Adolescence; Autoantibodies/AN; C-Peptide/BL; Child; Comparative Study; Cyclosporins/AE/*TU; Diabetes Mellitus, Insulin-Dependent/BL/*DT; Female; Follow-Up Studies; Glucagon/DU; Glucose Clamp Technique; Human; Insulin/BL/SE/*TU; Islets of Langerhans/IM; Male. .T Limited duration of remission of insulin dependency in children with recent overt type I diabetes treated with low-dose cyclosporin. .P JOURNAL ARTICLE. .W Preliminary data from our group indicated that cyclosporin A induced frequent remissions of insulin dependency in a group of 40 insulin-dependent (type I) diabetic children if given at the onset of clinical manifestations of diabetes. We report a 2-yr analysis of the response to cyclosporin A in the group of 81 patients included in the initial study. As observed before, a remission could be obtained in most of the patients (65%) in association with a shorter duration of symptoms, less severe hyperglycemia, lower incidence of ketoacidosis, and higher plasma C-peptide concentrations. All remissions ended during the follow-up period after a mean +/- SE duration of 316 +/- 21 days (range 31-850 days). Two parameters were linked to the duration of remissions: the mean circulating level of cyclosporin during the first 3 mo and the duration of prediagnostic polyuria. We were unable to relate the end of a remission to variations in the cyclosporin regimen, titer of autoantibodies, or progression of beta-cell failure. The euglycemic clamp technique revealed that insulin sensitivity decreases with time in patients not taking insulin. At 24 mo, the patients who had a remission of insulin dependency had better glycemic control, lower insulin dosages, and C-peptide levels two- to threefold higher than the nonremission patients and four- to sixfold higher than the historical control subjects. The cyclosporin regimen was well tolerated over the observed period: more specifically, serum creatinine remained unchanged, and kidney biopsies performed at 18-24 mo of treatment were within normal limits.(ABSTRACT TRUNCATED AT 250 WORDS) .A Bougneres PF; Landais P; Boisson C; Carel JC; Frament N; Boitard C; Chaussain JL; Bach JF. .I 275032 .U 91006895 .S Diabetes 9101; 39(10):1273-8 .M Animal; Autoimmune Diseases/*PA; Islets of Langerhans/*IM/PA; Macrophages/DE/*IM/PA; Mice; Mice, Inbred Strains; Necrosis; Pancreas Transplantation/*PA; Silica/TO; Support, Non-U.S. Gov't; T-Lymphocytes/IM; Transplantation, Isogeneic. .T Studies on autoimmunity for initiation of beta-cell destruction. VI. Macrophages essential for development of beta-cell-specific cytotoxic effectors and insulitis in NOD mice. .P JOURNAL ARTICLE. .W NOD mice were treated with silica (which is selectively toxic to macrophages) from 4 or 20.5 wk of age. Syngeneic neonatal pancreases were transplanted into the renal subcapsular space of the NOD mice at 21 wk of age. Silica treatment was continued until 24 wk of age, and then the mice were killed for examination of islet morphology. Neither the islets in transplanted pancreases nor the host pancreatic islets from the early long-term silica-treated animals revealed insulitis. In contrast, most of the islets in transplanted pancreases from the late short-term silica-treated animals showed severe insulitis and beta-cell necrosis, as did the host islets. A further experiment was performed to compare the effect of late short-term silica treatment with that of anti-L3T4-antibody treatment of the same time and duration. In contrast to the late short-term silica-treated animals, the transplanted pancreases in the anti-L3T4-antibody-treated animals revealed intact islets, although most of the host islets showed insulitis. The control group, which received no treatment but did receive neonatal pancreases, revealed severe insulitis and beta-cell necrosis of both transplanted and host islets. These results suggest that early macrophage depletion can abolish the development of beta-cell-specific immunologic effectors but that late macrophage depletion, after the development of insulitis, does not affect the destruction of beta-cells by preexisting effectors other than macrophages. We conclude that macrophages are essential for the development of beta-cell-specific cytotoxic effectors in the initial phase of insulitis in NOD mice. .A Ihm SH; Yoon JW. .I 275033 .U 91006896 .S Diabetes 9101; 39(10):1279-88 .M Animal; Cells, Cultured; Diabetes Mellitus, Experimental/GE/*IM; Electrophoresis, Polyacrylamide Gel; Female; Fluorescent Antibody Technique; Genes, Structural/*; Histocompatibility Antigens/*GE; Isoantigens/*GE; Lymph Nodes/IM; Lymphocytes/*IM; Male; Rats; Rats, Inbred Lew; Rats, Inbred Strains; Rats, Inbred WF; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Biochemical studies of RT6 alloantigens in BB/Wor and normal rats. Evidence for intact unexpressed RT6a structural gene in diabetes-prone BB rats. .P JOURNAL ARTICLE. .W Lymphocytes bearing the T-lymphocyte differentiation antigen RT6 play an important immunoregulatory role in the development of autoimmune diabetes in BB rats. Immunofluorescence studies suggest that diabetes-prone (DP)- but not diabetes-resistant (DR)-BB rat lymphocytes fail to express RT6 antigen during ontogeny. Two alloantigenic forms of the molecule exist, i.e., RT6.1 and RT6.2; both are linked to cell membranes by a phosphatidylinositol (PI) linkage. In these studies, PI-phospholipase C (PLC) treatment of lymphocytes from BB and normal rats followed by immunoabsorption and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of released proteins with anti-RT6 allotype-specific monoclonal antibodies was performed. RT6.1 in several nondiabetic rat strains was found to consist of a family of nonglycosylated and variably glycosylated molecules: an N-Glycanase-resistant 24,000- to 26,000-Mr peptide and four N-Glycanase-sensitive peptides of 29,000, 31,000, 33,000, and 34,000 Mr. In contrast, RT6.2 was found to be a 24,000- to 26,000-Mr nonglycosylated polypeptide. The electrophoretic pattern of RT6.1 was observed to be the same when the antigen was extracted from W3/25+ (CD4+) versus W3/25- T lymphocytes or from resting versus mitogen-activated cells. A pattern of bands characteristic of the RT6.1 antigen found in normal rat strains was detected after PLC treatment or detergent solubilization of lymphocytes obtained from DR rats. In contrast, no evidence of either RT6 species was found after PLC or detergent treatment of comparable numbers of T lymphocytes from DP-BB rats. Interestingly, T lymphocytes from Wistar-Furth (RT6.2+) x DP (RT6-) F1 crosses were observed to coexpress both RT6.2 and RT6.1 molecules, with the electrophoretic pattern of RT6.1 being similar to that obtained in DR and other rat strains. This study provides biochemical evidence that DP rats may have an intact RT6a structural gene. .A Crisa L; Greiner DL; Mordes JP; MacDonald RG; Handler ES; Czech MP; Rossini AA. .I 275034 .U 91006897 .S Diabetes 9101; 39(10):1289-97 .M Animal; Antihypertensive Agents/*PD; Blood Glucose/*ME; Dynorphin/AN/*PD; Glucagon/AN; Glucose Tolerance Test; Immunoenzyme Techniques; In Vitro; Insulin/BL/*SE; Islets of Langerhans/CY/DE/*SE; Mice; Mice, Obese; Peptide Fragments/*PD; Pyrrolidines/*PD; Reference Values; Support, Non-U.S. Gov't. .T Increased sensitivity to insulin-releasing and glucoregulatory effects of dynorphin A1-13 and U 50488h in ob/ob versus lean mice. .P JOURNAL ARTICLE. .W The effects of two kappa-opiate agonists, U 50488h and dynorphin A1-13, on plasma insulin and glucose concentrations in vivo and insulin release in vitro were tested in fasted genetically obese (ob/ob) and lean (+/+) mice at 12-15 wk of age. Fasting plasma insulin concentrations in ob/ob and lean mice were 1.22 +/- 0.10 and 0.23 +/- 0.05 nM, and plasma glucose levels were 6.90 +/- 0.84 and 4.70 +/- 0.29 mM, respectively. Administration of U 50488h (1 mg/kg body wt i.p.) to ob/ob mice dramatically raised plasma insulin by 670 and 790 pM at 15 and 30 min. Plasma glucose was raised from 5 min onward to a maximum increment of 4.2 mM above baseline. These effects were blocked by simultaneous administration of naloxone (10 mg/kg). A higher dose of U 50488h (10 mg/kg body wt i.p.) was required to produce significant increases in lean mouse plasma insulin (81 pM at 15 min) and glucose (0.7, 1.1, and 1.7 mM at 5, 15, and 30 min, respectively). Dynorphin (1 mg/kg body wt i.p.) raised plasma insulin in ob/ob mice by 380 and 410 pM at 15 and 30 min and raised plasma glucose by 1.6 mM at 15 min. In lean mice, the same dose of dynorphin had no effect on plasma insulin concentrations but induced a small rise in glucose. In ob/ob mice, the agonist-induced rise in glucose did not cause the insulin response, because insulin levels were not elevated by a glucose challenge.(ABSTRACT TRUNCATED AT 250 WORDS) .A Khawaja XZ; Green IC; Thorpe JR; Bailey CJ. .I 275035 .U 91006898 .S Diabetes 9101; 39(10):1298-304 .M Animal; Antibodies, Monoclonal/IM/TU; Autoimmune Diseases/*GE; Blood Glucose/ME; Diabetes Mellitus, Experimental/BL/*IM/PC; H-2 Antigens/*GE/IM; Histocompatibility Antigens Class II/*GE; Islets of Langerhans/DE/PA; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Recombination, Genetic; Reference Values; Streptozotocin/TO. .T Genetic control by I-A subregion in H-2 complex of incidence of streptozocin-induced autoimmune diabetes in mice. .P JOURNAL ARTICLE. .W An experimental autoimmune diabetes in mice characterized by delayed-onset hyperglycemia with lymphocytic infiltrations of the pancreatic islets can be induced by multiple administrations of low doses of streptozocin (STZ). We report on the influence of the MHC (H-2 complex) on this autoimmune diabetes by comparing the susceptibilities of various congenic and recombinant strains with a B10 background. In congenic strains, C57BL/10 (H-2b) and B10.BR (H-2k) mice showed a high incidence of diabetes, whereas B10.D2 (H-2d) and B10.S (H-2s) mice showed a low incidence. Therefore, we suggest that the H-2 complex influences diabetes susceptibility and that both b and k are high-susceptibility alleles, whereas d and s are low-susceptibility alleles. In recombinant strains, those with the same haplotypes on the K, E, S, and D subregions of the H-2 complex showed undefined (high and low) susceptibilities, indicating that the diabetes-susceptibility genes are located outside these loci. Strains possessing I-Ab or I-Ak gene products (C57BL/10, B10.BR, B10.TL, B10.A, and B10.A(2R] showed high incidences, whereas strains possessing I-Ad or I-As (B10.D2, B10.S, B10.S(7R), B10.S(9R), and B10.GD) showed low incidences. In addition, administration of anti-I-A monoclonal antibody prevented the manifestation of diabetes in STZ-administered mice. Passive transfer of STZ-administered T lymphocytes to mice given minute doses of STZ induced significant hyperglycemia. This successful transfer was only observed in H-2-compatible mice. Thus, we conclude that one gene coding for susceptibility to this experimental diabetes was located in the I-A subregion within the H-2 complex. .A Tanaka S; Nakajima S; Inoue S; Takamura Y; Aoki I; Okuda K. .I 275036 .U 91006899 .S Diabetes 9101; 39(10):1305-12 .M Animal; Aqueous Humor/ME; Blood Glucose/ME; Cornea/ME; Diabetes Mellitus, Experimental/BL/*ME; Diabetes Mellitus, Insulin-Dependent/ME; Diabetes Mellitus, Non-Insulin-Dependent/ME; Inositol/BL/*ME; Kidney/ME; Myocardium/ME; Rabbits; Reference Values; Retina/ME; Sorbitol/*ME; Support, U.S. Gov't, P.H.S.. .T Diabetes and the myo-inositol paradox. .P JOURNAL ARTICLE. .W To test the general applicability of the hypothesis that diabetes mellitus causes increased polyol pathway activity, decreased tissue free myo-inositol, and resultant pathological changes in tissues susceptible to the ravages of diabetes, we measured glucose, sorbitol, and myo-inositol with quantitative histochemical techniques in layers of the cornea, the aortic myointima, the cardiac left ventricle and atrioventricular node (AVN), and retina and kidney after 19 days or 2 mo (mildly diabetic non-insulin-treated [MD] and severely diabetic insulin-treated [SD] groups) in the alloxan-induced diabetes model. In the aqueous humor, glucose rose linearly with increased serum glucose, sorbitol was markedly increased in the MD and SD groups, and myo-inositol did not change in any diabetic group. There was no change in glucose or sorbitol in aortic myointima in any group, but myoinositol was decreased in 19-day diabetic rabbits by 26%, unchanged in MD rabbits but paradoxically increased by 60% in SD rabbits. Glucose, sorbitol, and myo-inositol increased in all three corneal layers in SD rabbits but only in epithelium and stroma in 19-day and MD rabbits. AVN glucose and sorbitol did not change in 19-day diabetic, MD, or SD diabetic rabbits. AVN myo-inositol was three times higher than ventricular myo-inositol and did not appear to change in SD rabbits. Retinal pigmented epithelium myo-inositol was decreased 30% in SD rabbits. Glomerular myo-inositol was also decreased, but not significantly, in SD rabbits. We conclude that the paradoxical increase in corneal and aortal myo-inositol raises fundamental questions about the general applicability of the myo-inositol-depletion hypothesis. .A Loy A; Lurie KG; Ghosh A; Wilson JM; MacGregor LC; Matschinsky FM. .I 275037 .U 91007072 .S Gastroenterology 9101; 99(5):1257-64 .M Adult; Chest Pain/*ET; Edrophonium/DU; Esophageal Motility Disorders/*PP; Esophagus/*PP; Female; Gastroesophageal Reflux/*PP; Human; Hydrogen-Ion Concentration; Male; Manometry; Middle Age; Pain Measurement; Pressure; Time Factors. .T Analysis of 24-hour esophageal pressure and pH data in unselected patients with noncardiac chest pain. .P JOURNAL ARTICLE. .W Fourty-four unselected patients with noncardiac chest pain were studied using conventional manometry with additional edrophonium provocation and 24-hour ambulatory esophageal pH and pressure recording with a system developed by our group. New, fully automated techniques of statistical analysis of the complete set of esophageal pressure and pH signals were used to examine the temporal relation between pain, esophageal motility disturbances, and gastroesophageal reflux. The analysis used the 97.5th percentile of amplitude and duration of all esophageal contractions in each patient as well as a chi 2 test of the distribution of contraction types to determine whether a pain episode was related to abnormal motility or not. The edrophonium test results were positive in 2 patients. Only 25 patients (56.8%) had at least one pain episode (total, 111 episodes) during 24-hour recording. Thirty-three percent of the pain episodes were related to reflux and 23.4% to abnormal motility, and 43.2% were not related to an esophageal function disturbance. In the patient-oriented analysis in this study, it was required for a positive correlation that the symptom index (percentage of related pain episodes) was higher than 75%. It was found that the pain was related to reflux in 2 patients (4.6%), to reflux and motor abnormalities in 4 (9.2%), and to motor abnormalities in 2 patients (4.6%). In 36 patients (81.8%), no relation with an esophageal abnormality could be established, either because the patients had no pain during the 24-hour study, or because the pain seemed unrelated to reflux or abnormal motility. .A Breumelhof R; Nadorp JH; Akkermans LM; Smout AJ. .I 275038 .U 91007073 .S Gastroenterology 9101; 99(5):1265-8 .M Deglutition; Diaphragm/*PH; Electromyography; Esophagogastric Junction/*PH; Human; Hydrogen-Ion Concentration; Manometry; Muscle Relaxation; Pressure; Reference Values; Support, U.S. Gov't, P.H.S.. .T Electrical and mechanical inhibition of the crural diaphragm during transient relaxation of the lower esophageal sphincter. .P JOURNAL ARTICLE. .W Electrical and mechanical correlates of crural diaphragm activity during swallow-induced and transient lower esophageal sphincter relaxation were monitored in 12 healthy subjects. Simultaneous esophageal manometric, pH, and crural diaphragm electromyogram recordings were performed for 1 hour in the postprandial period. Swallow-induced lower esophageal sphincter relaxation was associated with minimal inhibition of the crural diaphragm, but transient lower esophageal sphincter relaxation was accompanied by marked inhibition of the crural diaphragm. The degree of lower esophageal sphincter relaxation appeared to correlate with the degree of crural diaphragm inhibition during transient lower esophageal sphincter relaxation. Inhibition of crural diaphragm during transient lower esophageal sphincter relaxation may play an important role in facilitating flow across the gastroesophageal junction. .A Mittal RK; Fisher MJ. .I 275039 .U 91007074 .S Gastroenterology 9101; 99(5):1269-74 .M Adult; Aged; Barium/DU; Biomechanics; Cricoid Cartilage/PH/*PP/RA; Deglutition; Female; Human; Larynx/PH/*PP/RA; Male; Manometry; Middle Age; Muscle Relaxation; Pharynx/PH/*PP/RA; Pressure; Support, U.S. Gov't, P.H.S.. .T Biomechanics of cricopharyngeal bars. .P JOURNAL ARTICLE. .W Patients with a prominent cricopharyngeal bar visible on radiography are generally considered to have spasm of the cricopharyngeus, which is the major muscle component of the upper esophageal sphincter. This condition has been termed "cricopharyngeal achalasia." The aim of this study was to determine the pathogenesis of cricopharyngeal bars. Concurrent videofluoroscopic and manometric examinations of the pharynx and upper esophageal sphincter were performed in a cohort of six patients with prominent cricopharyngeal bars and in eight control volunteers. In each subject, swallows of 2-30-mL barium boluses were recorded. The patients with cricopharyngeal bars showed (a) normal peristaltic contraction in the pharynx, (b) normal axial upper esophageal sphincter pressure and relaxation, (c) normal flow rate across the upper esophageal sphincter, and (d) normal duration of upper esophageal sphincter opening for different bolus volumes. The major abnormalities in the patients with cricopharyngeal bars were (a) reduced maximal dimensions of the upper esophageal sphincter during the transsphincteric flow of barium and (b) increased intrabolus pressure upstream to the upper esophageal sphincter. Thus, the increase in intrabolus pressure preserved normal transsphincteric flow rates even though the upper esophageal sphincter did not open normally. Overall, the constellation of findings in the patients studied suggests that the underlying pathogenesis of their cricopharyngeal bar was reduced muscle compliance wherein the relaxed cricopharyngeus did not distend normally during swallowing. .A Dantas RO; Cook IJ; Dodds WJ; Kern MK; Lang IM; Brasseur JG. .I 275040 .U 91007075 .S Gastroenterology 9101; 99(5):1275-82 .M Analysis of Variance; Fasting; Female; Gastric Emptying/*PH; Gastrointestinal Motility/*PH; Human; Male; Myoelectric Complex, Migrating/*PH; Phenols; Pyloric Antrum/PH; Reference Values; Solutions; Support, Non-U.S. Gov't. .T The influence of the interdigestive migrating myoelectric complex on the gastric emptying of liquids. .P JOURNAL ARTICLE. .W It is unknown how the interdigestive migrating motor complex influences the gastric emptying of liquids. Therefore, the gastric emptying rate of 50- and 200-mL volumes of phenol red solution were measured while monitoring contractile activity. Motor activity was recorded using a hydraulic manometric system and expressed as either the proximity of dosing time to time of appearance of phase III or as a motility index, defined as (contractile area)/(sampling interval time). After an initial lag period, emptying was log linear. With a 50-mL oral dose, the mean gastric emptying rate of the log-linear phase was successively faster during phase I (0.018 +/- 0.003 min-1), phase II (0.083 +/- 0.031 min-1), and late phase II/III (0.171 +/- 0.066 min-1) (P less than 0.05). Similarly, the mean lag time decreased successively with phases I, II, and late II/III (19.1 +/- 12.4, 7.6 +/- 5.6, and 3.8 +/- 2.8 minutes, respectively). At a 200-mL oral dose, there was no difference in the emptying rate between phase I and phase II (0.104 +/- 0.0014 vs. 0.110 +/- 0.041 min-1), but the emptying rate during late phase II/III was significantly greater (0.236 +/- 0.069 min-1); lag time was not dependent on phase. There was a statistical difference in the overall mean emptying rate between the 50- and 200-mL volumes. Also, during phase I, the emptying rate was faster for the 200-mL volume. This study shows a strong dependence of liquid gastric emptying rate and lag time on interdigestive antral motility, the emptying of small volumes being more dependent on motility phase than that of large volumes. Phase-related fluctuations in contractile activity can account for much of the reported variability in gastric emptying data. Furthermore, this study suggests that dose volume and interdigestive motor activity at the time of drug administration can affect absorption and onset of therapeutic response for some drugs. .A Oberle RL; Chen TS; Lloyd C; Barnett JL; Owyang C; Meyer J; Amidon GL. .I 275041 .U 91007076 .S Gastroenterology 9101; 99(5):1283-91 .M Animal; Biopsy; Chromatography, Gel; Gastric Mucosa/*ME; Human; Immune Sera; Immunohistochemistry; Intestinal Mucosa/*ME; Male; Pancreas/*ME; Protein Precursors/*ME; Radioimmunoassay; Rats; Rats, Inbred Strains; Somatostatin/*ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Distribution of somatostatin-14 and somatostatin-28 gastrointestinal-pancreatic cells of rats and humans. .P JOURNAL ARTICLE. .W Somatostatin-14 and somatostatin-28 are biologically active peptides derived from the posttranslational cleavage of prosomatostatin. Because both peptides are found in variable concentrations in the gastrointestinal (GI) tract and pancreas, it has been contended that somatostatin-28 is either an intermediate in the processing to somatostatin-14 or a terminal product derived from prosomatostatin. To address this question, two antisera were used to recognize epitopes in two regions of somatostatin-14; one with high specificity for somatostatin-14 and the other interacting with prosomatostatin, somatostatin-28, and somatostatin-14. Distribution of these peptides was measured in extracts of pancreas and mucosa and submucosa/muscularis from the rat and human GI mucosal biopsies; the antisera were used to immunostain cells in these tissues. Extracts of human and rat intestinal mucosa contained both somatostatin-28 and somatostatin-14. By immunocytochemistry, D cells in stomach and pancreas and neural processes in the intestine, extending into the mucosal villi adjacent to endocrine cells, stained with both antisera indicating the presence of somatostatin-14, prosomatostatin, and possibly somatostatin-28. In contrast, endocrine cells in the gut reacting with antisera against somatostatin-28 did not immunostain with somatostatin-14-specific antisera. Thus, these data suggest that somatostatin-28 is the terminal peptide processed from prosomatostatin in intestinal mucosal cells, whereas somatostatin-14 is the major final product in gastric and pancreatic D cells and neurons. The localization of somatostatin-28 and somatostatin-14 in different cells in the pancreas and GI tract implies that they serve different functions. .A Francis BH; Baskin DG; Saunders DR; Ensinck JW. .I 275042 .U 91007077 .S Gastroenterology 9101; 99(5):1292-6 .M Animal; Dogs; Female; Gastric Mucosa/CH/*ME; Human; Phosphatidylcholines/AN/*ME; Phospholipids/AN/*ME; Rats; Rats, Inbred Strains; Stomach Ulcer/ET; Support, Non-U.S. Gov't. .T Phospholipids from rat, human, and canine gastric mucosa. Composition and metabolism of molecular classes of phosphatidylcholine. .P JOURNAL ARTICLE. .W To validate a recent proposal that a phospholipid lining with a high content of dipalmitoylphosphatidylcholine may protect gastric mucosa against luminal acid, it was decided to study composition and metabolism of phospholipids in the gastric mucosa. Phospholipids were analyzed in rat, human, and dog gastric mucosal surface tissue and in a chloroform/methanol-lavage of rat and canine stomach. Phosphatidylcholine and phosphatidylethanolamine were the main components. Saturated fatty acids were almost exclusively esterified at the sn-1 position of the glycerol moiety of phosphatidylcholine, and unsaturated fatty acids mainly at the sn-2 position. The disaturated class of phosphatidylcholine comprised 2%-6% of total phosphatidylcholine. Precursors of phosphatidylcholine, i.e., [32P]orthophosphate and [methyl-14C]choline, were preferentially incorporated into the disaturated molecular class 0.5-6 hours after IV administration. It can be speculated that disaturated phosphatidylcholine, although quantitatively a minor component, is specifically triggered in mucosal renewal processes. .A Schmitz MG; Renooij W. .I 275043 .U 91007078 .S Gastroenterology 9101; 99(5):1297-302 .M Animal; Atropine/PD; Bombesin/*PD; Comparative Study; Gastrins/ME/*PH; Male; Models, Neurological; Neural Pathways/DE; Rats; Somatostatin/*ME; Stomach/IR; Support, U.S. Gov't, P.H.S.; Tetrodotoxin/PD; Time Factors. .T Role of gastrin in bombesin-stimulated somatostatin release. .P JOURNAL ARTICLE. .W The intermediary pathways in the bombesin-induced somatostatin release were examined in isolated perfused rat stomach obtained from male rats that were fasted overnight. The stomachs were perfused by way of the celiac artery. On coinfusion of 1.0 mumol/L tetrodotoxin and 1 nmol/L bombesin, a significant depression in release of somatostatin was observed compared with that observed with bombesin alone. The 5-minute integrated somatostatin response after treatment with tetrodotoxin and bombesin was 173% +/- 14% of basal, which was significantly lower than that observed with bombesin alone (394% +/- 59% of basal, P less than 0.05) but significantly higher than that observed with medium-199 alone (95% +/- 7% of basal, P less than 0.05); this indicated that approximately 70% of the bombesin-stimulated somatostatin release was indirectly mediated through neural pathways, while a significant (approximately 30%) segment of it was mediated by nonneural mechanisms. To test if the 30% somatostatin release was secondary to gastrin release in response to bombesin, gastrin antiserum and bombesin (1 nmol/L) were coadministrated in the presence or absence of tetrodotoxin (1 mumol/L). Gastrin antiserum alone did not significantly affect basal release of somatostatin but caused a significant inhibition (approximately 23%) of bombesin-provoked somatostatin release. Coadministration of gastrin antiserum and tetrodotoxin attenuated bombesin-stimulated somatostatin release. Gastrin (1 mumol/L) alone significantly stimulated somatostatin release (150% +/- 10% of basal), which was completely attenuated in the presence of gastrin antiserum. Tetrodotoxin did not affect bombesin-elicited gastrin release, confirming that bombesin-stimulated gastrin release was directly mediated. To determine the nature of the neural pathways mediating the bombesin-induced somatostatin release, atropine (100 nmol/L) was used. Atropine inhibited bombesin-induced somatostatin release to the same extent as tetrodotoxin, indicating that cholinergic pathways mediated bombesin-induced somatostatin release. These results show that almost all the somatostatin response to bombesin is indirectly mediated, and is composed of a major neural (cholinergic) and a minor nonneural pathway. The nonneural mechanism appears to be contributed primarily by gastrin released in response to bombesin, which apparently has a short paracrine positive feedback effect on somatostatin release. .A Guo YS; Thompson JC; Singh P. .I 275044 .U 91007079 .S Gastroenterology 9101; 99(5):1303-6 .M Adult; Alcohol, Ethyl/AD/*TU; Comparative Study; Electrocoagulation/*; Endoscopy, Gastrointestinal; Female; Gastrointestinal Hemorrhage/DI/ET/*TH; Human; Injections, Intralesional; Male; Middle Age; Peptic Ulcer/*CO/DI; Prospective Studies; Recurrence; Sclerotherapy/*. .T Multipolar electrocoagulation versus injection therapy in the treatment of bleeding peptic ulcers. A prospective, randomized trial. .P CLINICAL TRIAL; JOURNAL ARTICLE. .W This study prospectively compares multipolar electrocoagulation and injection therapy in high-risk patients with bleeding ulcers. Patients were considered for entry if they had a bloody nasogastric aspirate, melena, or hematochezia and unstable vital signs, transfusion of greater than or equal to 2 U of blood in 12 hours, or a decrease in hematocrit of greater than or equal to 6% in 12 hours. Sixty patients with endoscopic evidence of an ulcer with active bleeding (n = 26) or a nonbleeding visible vessel (n = 34) were randomly assigned to receive multipolar electrocoagulation or injection with absolute ethanol. Hemostasis was achieved in 14 of 14 actively bleeding patients with multipolar electrocoagulation vs. 10 of 12 (83%) treated with injection. No significant differences were observed between electrocoagulation and injection therapy in any parameter assessed during the hospitalization: incidence of further bleeding (6% vs. 10%), units of blood transfused after treatment (1.8 +/- 0.6 vs. 1.3 +/- 0.4), incidence of surgery for bleeding (6% vs. 7%), length of hospital stay in days (5.8 +/- 0.9 vs. 7.2 +/- 2.5), cost of hospitalization (+7160 +/- +1630 vs. +8520 +/- +2960), or mortality rate (3% vs. 3%). Treatment induced bleeding in nonbleeding visible vessels in 35% of subjects in each group, but this was controlled with continued treatment in all patients. One delayed perforation occurred 9 days after multipolar electrocoagulation. Multipolar electrocoagulation and injection therapy are of comparable efficacy in the treatment of patients with clinical evidence of a major upper gastrointestinal bleed and endoscopic evidence of an ulcer with active bleeding or a nonbleeding visible vessel. .A Laine L. .I 275045 .U 91007080 .S Gastroenterology 9101; 99(5):1307-14 .M Achlorhydria/BL/CO/*PA; Aged; Aged, 80 and over; Anemia, Pernicious/BL/CO/PA; Biopsy; Female; Gastric Fundus/*PA; Gastric Mucosa/*PA; Gastrins/BL; Gastritis, Atrophic/BL/CO/*PA; Gastroscopy; Human; Hyperplasia; Male; Middle Age; Schilling Test. .T Evolution of fundic argyrophil cell hyperplasia in nonantral atrophic gastritis. .P JOURNAL ARTICLE. .W Fundic argyrophil cells were studied for a mean period of 68.7 months (range, 11-170) in 18 patients with fundic atrophic gastritis and achlorhydria. Initially, 12 patients had hyperplasia of the argyrophil cells, the severity of which was assessed using a semiquantitative classification based on the number of argyrophil clusters per square millimeter. At the end of the study, the degree of hyperplasia was unchanged in 9 patients, had decreased in 2, and had increased in 1; no significant increase in the number of argyrophil clusters, precarcinoid changes, or carcinoid tumors were observed and the high level of gastrinemia [mean, 4.8 (range, 1.9-8.1) times the upper limit for normal) did not change significantly. Of the 6 patients with no hyperplasia at the outset of the study, 4 continued without hyperplasia and 2 presented a low-grade hyperplasia at the 20th and 130th month. Gastrinemia increased significantly in the last patient and stayed normal in the other 5. This study argues in favor of the stable appearance of fundic argyrophil cells in patients with atrophic gastritis and stable gastrinemia. .A Roucayrol AM; Cattan D. .I 275046 .U 91007081 .S Gastroenterology 9101; 99(5):1315-23 .M Acute Disease; Animal; Chronic Disease; Disease Models, Animal/*; Female; Gastric Fundus/MI/PA; Gastric Mucosa/MI/PA; Gastritis/MI/*PA; Helicobacter pylori/*; Helicobacter Infections/MI/*PA; Mice; Spirillum; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Time Factors. .T A small animal model of human Helicobacter pylori active chronic gastritis. .P JOURNAL ARTICLE. .W Isolation of a spiral-shaped bacterium closely related to Helicobacter pylori from the cat stomach made it possible to investigate new small animal models of gastric infection. Pure cultures of this bacterium, provisionally named "Helicobacter felis," were fed to germ-free mice. The organism colonized the stomach in large numbers in mucus and deep in the gastric pits and showed the same gastric trophism found with H. pylori. Significant histopathology was seen in all H. felis-infected mice. At 2 weeks postinfection, an acute inflammatory response was seen composed primarily of eosinophils and neutrophils. At 3 weeks, the polymorphonuclear response was more pronounced with large numbers of neutrophils in some areas forming small microabscesses. Lymphocytes also increased in number. By 8 weeks, several relatively large lymphoid nodules were present in the submucosa. Multiple small microabscesses were still present in the pyloric mucosa. This is the first animal model of bacterial gastritis to be described that shows progression from acute inflammation to persistent acute on chronic inflammation (active chronic) as is seen in human infection with H. pylori. .A Lee A; Fox JG; Otto G; Murphy J. .I 275047 .U 91007082 .S Gastroenterology 9101; 99(5):1324-32 .M Acetylcholine/*PD; Adolescence; Adult; Aged; Aged, 80 and over; Animal; Child; Colon; Comparative Study; Disease Models, Animal; Female; Histamine/*PD; Human; In Vitro; Inflammatory Bowel Diseases/PP; Leukotrienes/*PD; Male; Middle Age; Muscle Contraction/DE; Muscle Relaxation/DE; Muscle, Smooth/*DE/PP; Prostaglandins/*PD; Rabbits; Regression Analysis. .T A comparison in vitro of human and rabbit distal colonic muscle responses to inflammatory mediators. .P JOURNAL ARTICLE. .W The present study compared in vitro the motor responses of human and rabbit distal colonic longitudinal and circular muscle to acetylcholine, histamine, leukotrienes B4 and D4, and prostaglandins E2 and F2 alpha. The active and passive mechanical properties of these muscles were also evaluated. All muscle types were contracted by acetylcholine and histamine. Longitudinal muscle from both species was contracted by prostaglandin E2 and prostaglandin F2 alpha, although rabbit muscle was more sensitive. Prostaglandin E2 relaxed the majority of both human and rabbit circular muscle preparations that were studied. Prostaglandin F2 alpha first relaxed and then contracted circular muscle from both species. Leukotriene B4 had no effect on any tissue studied. Leukotriene D4 caused transient relaxations in a proportion of all muscle types, but the relaxations were not concentration-related. Contractile responses did not differ under isotonic recording conditions, but relaxations were much more clearly defined. Based on experiments using atropine, phentolamine and propranolol, and pyrilamine or tetrodotoxin, it was concluded that the responses of both human and rabbit distal colonic muscles to these inflammatory mediators have a similar pharmacological basis. All muscle types exhibited low passive tension and developed active tension in the range 0.8-1.2 Lo. These data strongly support the belief that after the onset of an induced colitis, the rabbit colon has value as a predictive model for the study of inflammatory mediator-induced colonic motility changes in humans. .A Percy WH; Burton MB; Fallick F; Burakoff R. .I 275048 .U 91007083 .S Gastroenterology 9101; 99(5):1333-8 .M Animal; Colony Count, Microbial; Cortisone/*AA/AD/PD; Disease Models, Animal; Enterocolitis, Pseudomembranous/BL/PA/*PC; Enzyme-Linked Immunosorbent Assay; Female; Human; Intestinal Mucosa/DE/MI/PA; Maternal-Fetal Exchange; Ovalbumin/BL; Pregnancy; Rats; Rats, Inbred Strains; Support, U.S. Gov't, P.H.S.. .T Prevention of necrotizing enterocolitis in the rat with prenatal cortisone. .P JOURNAL ARTICLE. .W Cortisone acetate is known to accelerate maturation of the immature intestine. The effect of prenatal administration of cortisone acetate on the morbidity and mortality of necrotizing enterocolitis was examined in a rat pup model. Pregnant rats were administered cortisone acetate, 20 mg/100 g of body weight, or normal saline by daily IP injection from day 18-21 of gestation. Rat pups were taken from the mothers before suckling was initiated, fed a simulated rat milk formula, and subjected to daily ischemic insults to produce an animal model of necrotizing enterocolitis. Both morbidity and the mortality rates were significantly improved with prenatal cortisone treatment. Maturation of the intestinal mucosal barrier was accelerated with the cortisone treatment as measured by decreased serum concentrations of a fed antigen, ovalbumin. Aerobic bacterial colonization of the small intestine and translocation of bacteria to the liver were decreased in the pups pretreated with steroids. These changes observed in a rat model of necrotizing enterocolitis may explain the decreased incidence of necrotizing enterocolitis in human infants born to mothers who received corticosteroids late in gestation. .A Israel EJ; Schiffrin EJ; Carter EA; Freiberg E; Walker WA. .I 275049 .U 91007084 .S Gastroenterology 9101; 99(5):1339-46 .M Adenosine Triphosphatase/AI/*AN; Animal; Antibodies, Monoclonal/PD; Colon/DE/*EN; Cross Reactions; Guinea Pigs; Imidazoles/PD; Ouabain/PD; Rabbits; Stomach/EN. .T The presence of H+,K(+)-ATPase in the crypt of rabbit distal colon demonstrated with monoclonal antibodies against gastric H+,K(+)-ATPase. .P JOURNAL ARTICLE. .W Indirect evidence indicates the presence of an active H+/K+ antiporter for the secretion of acid in the distal colon. It was examined whether the H+/K+ antiporter in the rabbit distal colon was hydrogen-potassium-stimulated adenosine triphosphatase (H+,K(+)-ATPase), which acts as a proton pump in the gastric mucosa. For this purpose, four monoclonal antibodies against hog gastric H+,K(+)-ATPase were raised. Three monoclonal antibodies dose-dependently inhibited the ouabain-insensitive gastric ATP-ase activity. Antibody HK4001 completely inhibited the ATPase activity. In indirect immunofluorescence studies, all four monoclonal antibodies stained H+,K(+)-ATPase in gastric mucosae of various animal species. Two monoclonal antibodies including antibody HK4001 cross-reacted with H+,K(+)-ATPase located in crypts of the transverse and descending colon and rectum of rabbits. Because the other two antibodies did not cross-react with the H+,K(+)-ATPase in the colon, this colonic enzyme is similar but not identical to gastric H+,K(+)-ATPase. On the other hand, HK4001 and SCH 28080 did not inhibit ouabain-sensitive K(+)-dependent ATPase activity in the guinea pig distal colon, and the antibodies did not stain the enzyme in the tissue. Therefore, ouabain-sensitive H+/K+ antiporter in the guinea pig is not similar to ouabain-insensitive rabbit colonic H+,K(+)-ATPase. .A Takeguchi M; Asano S; Tabuchi Y; Takeguchi N. .I 275050 .U 91007085 .S Gastroenterology 9101; 99(5):1347-51 .M Abscess/PC; Adolescence; Adult; Antibiotics/TU; Child; Crohn Disease/CO/DH/*DT; Drug Therapy, Combination; Female; Follow-Up Studies; Human; Male; Prednisone/TU; Rectal Diseases/PC; Rectal Fistula/PC; Salicylazosulfapyridine/TU; Time Factors; 6-Mercaptopurine/*AD. .T Long-term 6-mercaptopurine treatment in adolescents with Crohn's disease [see comments] .P JOURNAL ARTICLE. .W Although 6-mercaptopurine is often used to treat adolescents with intractable Crohn's disease, its long-term efficacy has not yet been studied in this population. This study shows data derived from 36 adolescents (mean age +/- SD, 16.5 +/- 3.3 years; 27 males, 9 females) treated at least 6 months with 6-mercaptopurine (1.5 mg.kg-1.day-1, maximum of 75 mg/day). Sites of Crohn's disease at the start of 6-mercaptopurine therapy included 17 ileocolic, 9 pancolic, 7 small bowel, and 3 partial colon. All had received corticosteroids, sulfasalazine, antibiotics, and nutritional support for 5.0 +/- 3.0 years before administering 6-mercaptopurine, but intractable symptoms persisted. Disease activity lessened during the first year of 6-mercaptopurine, reflected by a higher Lloyd-Still disease activity score (pre, 64 +/- 9 vs. 6-mercaptopurine, 72 +/- 11; P less than 0.0001). General activity, physical examination, nutrition, and laboratory subscores all improved (P less than 0.004). Lessened disease activity occurred despite concomitant decrease in duration of prednisone use (pre, 9.5 +/- 4.2 vs. 6-mercaptopurine, 6.6 +/- 4.9 months/year; P less than 0.001) and cumulative annual prednisone exposure (pre, 3672 +/- 2106 vs. 6-mercaptopurine, 1964 +/- 1460 mg; P less than 0.0007). The frequency of perianal fistulae and abscesses also decreased (P less than 0.01) during treatment. Annual rates of hospitalization decreased in 44% of subjects during 6-mercaptopurine treatment, while increasing in only 22%. Follow-up beyond 1 year of 6-mercaptopurine treatment showed continued remission in 23 of 30 subjects. No serious complications were seen. 6-mercaptopurine is an effective long-term therapy for adolescents with intractable Crohn's disease. While inducing remission, it also has a significant steroid-sparing effect which may be of particular benefit to this population. .A Markowitz J; Rosa J; Grancher K; Aiges H; Daum F. .I 275051 .U 91007086 .S Gastroenterology 9101; 99(5):1352-7 .M Adenosine/PD; Adenosine Triphosphate/PD; Analysis of Variance; Animal; Anthraquinones/*PD; Calcitonin Gene-Related Peptide/PD; Capsaicin/PD; Cathartics/*PD; Electric Stimulation; Female; Mesenteric Arteries/IR; Rats; Rats, Inbred Strains; Senna/*PD; Splanchnic Circulation/*DE; Substance P/PD; Support, Non-U.S. Gov't; Time Factors; Vasoconstriction/DE. .T Effects of long-term laxative treatment on rat mesenteric resistance vessel responses in vitro. .P JOURNAL ARTICLE. .W The effects of long-term treatment with the laxatives senna and 1,8-dihydroxyanthraquinone (danthron) were investigated in isolated mesenteric vascular beds of rats. The senna was administrated as ground senna pods mixed with milk chocolate. Danthron was also administered in this way. Chocolate-fed, senna-fed, and danthron-fed rats were supplied with usual feed, supplemented with chocolate, chocolate adulterated with ground senna pods, and chocolate adulterated with danthron, respectively. A group of control rats had no supplement. Perivascular nerve stimulation elicited frequency-dependent vasoconstriction of the mesenteric bed. There were no significant differences in responsiveness to perivascular nerve stimulation among mesenteric beds from the four groups. During two separate consecutive applications of capsaicin, a sensory neurotoxin, pressor responses to nerve stimulation of vascular beds from the control and chocolate-fed rats were inhibited on both occasions. However, in mesenteric beds from the senna-fed and danthron-fed groups, inhibition of pressor responses was the same on the first application of capsaicin as in the control and chocolate-fed groups, but the effect of the second application of capsaicin was greatly reduced. Calcitonin gene-related peptide, adenosine 5'-triphosphate, and adenosine mimicked the inhibitory action of capsaicin on nerve stimulation in all groups, while substance P was without effect. There was no significant difference in responsiveness to these agents among the four groups. These results suggest that senna or its metabolites may cause a sensory neuropathy of mesenteric resistance vessels and that calcitonin gene-related peptide, adenosine 5'-triphosphate, and adenosine, but not substance P, are possible candidates as mediators of the inhibitory effects induced by capsaicin. .A Ralevic V; Hoyle CH; Burnstock G. .I 275052 .U 91007087 .S Gastroenterology 9101; 99(5):1358-63 .M Analysis of Variance; Animal; Benzopyrans/PD; Cats; Granulocytes/*PH; Indoles/PD; Intestinal Mucosa/*BS; Ischemia/ME/*PP; Leukotrienes B/AI/*BI; Nordihydroguaiaretic Acid/PD; Radioimmunoassay; Reperfusion Injury/ME/*PP; Support, U.S. Gov't, P.H.S.. .T Role of leukotriene B4 in granulocyte infiltration into the postischemic feline intestine. .P JOURNAL ARTICLE. .W Several studies have demonstrated that granulocytes accumulate in the intestinal mucosa following ischemia/reperfusion. It has been suggested that leukotriene B4 may be released during ischemia/reperfusion and consequently may promote granulocyte infiltration into the mucosa. The objectives of this study were to determine whether (a) leukotriene B4 is produced in the gut mucosa during ischemia and reperfusion, and (b) inhibition of leukotriene B4 attenuates granulocyte infiltration into the postischemic intestinal mucosa. Isolated segments of cat intestine were subjected to 3 hours of ischemia and 1 hour of reperfusion. Mucosal samples were obtained during baseline, ischemia at 3 hours and reperfusion at 1 hour. Leukotriene B4 production was determined by radioimmunoassay. Tissue-associated myeloperoxidase activity was used to quantitate granulocyte accumulation in the mucosal samples. In untreated animals, mucosal leukotriene B4 concentration was higher at reperfusion compared with baseline levels. The reperfusion-induced increase in mucosal leukotriene B4 was entirely prevented by pretreatment with either nordihydroguaiaretic acid (Sigma Chemical Co., St. Louis, MO) or L663,536 (Merck-Frosst, Montreal, Quebec, Canada), two potent lipoxygenase inhibitors. Both lipoxygenase inhibitors, as well as leukotriene B4 antagonist (SC-41930) significantly attenuated the reperfusion-induced infiltration of granulocytes. These results indicate that leukotriene B4 plays an important role in mediating the granulocyte accumulation elicited by reperfusion of the ischemic bowel. .A Zimmerman BJ; Guillory DJ; Grisham MB; Gaginella TS; Granger DN. .I 275053 .U 91007088 .S Gastroenterology 9101; 99(5):1364-71 .M Animal; Antibodies; Antibodies, Monoclonal; Central Nervous System/*CH; Intermediate Filament Proteins/*AN; Intermediate Filaments/*CH; Microscopy, Fluorescence; Myenteric Plexus/*CH; Neurons/*CH; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Neurofilament immunoreactivity in myenteric neurons differs from that found in the central nervous system. .P JOURNAL ARTICLE. .W Neurofilaments are 10-nm diameter protein fibers found within neurons and are composed predominantly of a triplet of polypeptides usually referred to as low-, medium-, and high-molecular-weight subunits. We describe the results of a study of myenteric plexus neurons using a panel of neurofilament triplet protein antibodies and indirect immunofluorescence techniques. Polyclonal antibodies to each of the three neurofilament subunits reliably stained myenteric neurons and their processes, indicating the presence of all three proteins in these cells. However, several well-characterized monoclonal antibodies to epitopes on high- and medium-molecular-weight subunits showed immunoreactivity in brain tissue but not in myenteric neurons and their processes. Some of the antibodies that do not stain recognize only phosphorylated epitopes, indicating that the level of neurofilament phosphorylation is very low in enteric neurons. Other antibodies that are not thought to be sensitive to the level of neurofilament phosphorylation show reduced or no staining of enteric neurons, suggesting the presence of immunologically distinct neurofilaments in these cells. These results suggest the presence of modified neurofilament structures in enteric neurons, possibly reflecting their unique mechanical character within the moving intestinal wall. .A Eaker EY; Shaw G; Sninsky CA. .I 275054 .U 91007089 .S Gastroenterology 9101; 99(5):1372-9 .M Adult; Aged; Aged, 80 and over; Analysis of Variance; Anus/*PP; Comparative Study; Constipation/CO; Fecal Incontinence/CO/ET/*PP; Female; Human; Male; Manometry; Middle Age; Pressure; Rectum/*PP; Sensation/PH; Spinal Cord Diseases/*CO/PP. .T Anorectal function in incontinent patients with cerebrospinal disease. .P JOURNAL ARTICLE. .W Anorectal manometry and the electrical activity of the external anal sphincter were measured in 20 patients with well-defined, incomplete spinal lesions who were referred because of fecal incontinence and in 30 normal subjects. Six patients had a high spinal lesion, 11 had a low spinal lesion, and 3 had mixed high and low spinal lesions. Patients with high spinal lesions had normal basal pressures but abnormally low squeeze pressures and impaired rectal sensation. Unlike normal subjects, there was no relationship between the depth of sphincter relaxation and the distention volumes. The external sphincter responses to rectal distention and increases in intraabdominal pressure were enhanced, and leakage of perfusion fluid was uncommon. Patients with low spinal lesions had abnormally low basal and squeeze pressures, blunted rectal sensation, and showed impaired external anal sphincter responses to rectal distention or increases in intraabdominal pressures. Most of these patients leaked the infused fluid during these maneuvers. Sphincter function in patients with mixed lesions was more severely impaired than in patients with low and high spinal lesions. Patients with mixed lesions showed abnormally low basal and squeeze pressures, impaired rectal sensation, and no external anal sphincter responses to either rectal distention or increases in intraabdominal pressure. Leakage occurred during these maneuvers in all patients with mixed lesions. .A Sun WM; Read NW; Donnelly TC. .I 275055 .U 91007090 .S Gastroenterology 9101; 99(5):1380-7 .M alpha 1-Antitrypsin/AN/*ME; Adolescence; Adult; Aged; Aged, 80 and over; Comparative Study; Diarrhea/*ME; Feces/*CH; Female; Gastrointestinal Diseases/*ME; Human; Male; Middle Age; Regression Analysis; Serum Albumin/AN/ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Alpha 1-antitrypsin excretion in stool in normal subjects and in patients with gastrointestinal disorders. .P JOURNAL ARTICLE. .W Fecal clearance of plasma alpha 1-antitrypsin is used as a measure of protein leakage into the intestinal tract. In this study, the alpha 1-antitrypsin concentration in stool and the plasma clearance of alpha 1-antitrypsin in normal subjects and in a consecutive series of patients with chronic diarrhea, malabsorption, or unexplained hypoalbuminemia was determined. The normal subjects were studied in their usual state and also when they had diarrhea secondary to ingestion of lactulose, sorbitol, sodium sulfate, or phenolphthalein. The study first concluded that induced diarrhea can cause an increase in alpha 1-antitrypsin clearance; if this is not considered in establishing normal values, there may be an overdiagnosis of excess protein leakage in patients with diarrhea. Second, there is a highly significant statistical correlation (P less than 0.001) between alpha 1-antitrypsin clearance and serum albumin concentration. On average, the serum albumin falls below 3.0 g/dL (30 g/L) when the alpha 1-antitrypsin clearance exceeds 180 mL/day, a value that is about threefold higher than the upper limit of normal. Third, three of nine patients with microscopic/collagenous colitis had elevated clearance of alpha 1-antitrypsin; by contrast, abnormal alpha 1-antitrypsin clearance was not found in 23 patients with idiopathic secretory diarrhea. Fourth, fecal alpha 1-antitrypsin concentration is not a reliable index of abnormal alpha 1-antitrypsin clearance. .A Strygler B; Nicar MJ; Santangelo WC; Porter JL; Fordtran JS. .I 275056 .U 91007091 .S Gastroenterology 9101; 99(5):1388-95 .M Adolescence; Adult; Aged; Balloon Dilatation; Blood Transfusion; Combined Modality Therapy; Double-Blind Method; Esophageal and Gastric Varices/*CO; Female; Gastrointestinal Hemorrhage/*DT/ET/TH; Human; Injections, Intravenous; Male; Middle Age; Somatostatin/AD/*TU. .T Randomized, double-blind, placebo-controlled trial of somatostatin for variceal bleeding. Emergency control and prevention of early variceal rebleeding. .P CLINICAL TRIAL; JOURNAL ARTICLE. .W A randomized, double-blind, placebo-controlled trial of somatostatin was conducted among 120 patients admitted for bleeding esophageal varices (59 placebo, 61 somatostatin). An initial 250-micrograms bolus of somatostatin followed by a 5-day continuous infusion of 250 micrograms/h and an identical administration of placebo were evaluated for both the control of bleeding and prevention of early rebleeding from varices. Failure to control bleeding occurred in 22 (36%) somatostatin patients vs. 35 (59%) placebo patients, with time to failure occurring earlier with placebo (P = 0.036). blood and plasma transfused per hour during drug infusion of trial drug was reduced in the somatostatin group: median 0.033 vs. 0.105 unit/h (P = 0.025). Use of balloon tamponade was halved in somatostatin-treated patients. The average effect of somatostatin was a 41% reduction in the hazard of failure (95% confidence interval, -1% to 65%, P = 0.0545) after adjustment for the severity of liver disease, which was the only other variable having a significant influence on time to failure. There was no difference in 30-day mortality per admission (7 placebo, 9 somatostatin) or complications. It is concluded that somatostatin is safe and more effective than placebo for the control of variceal bleeding. .A Burroughs AK; McCormick PA; Hughes MD; Sprengers D; D'Heygere F; McIntyre N. .I 275057 .U 91007093 .S Gastroenterology 9101; 99(5):1401-7 .M Adult; Aged; Blood Pressure/DE; Double-Blind Method; Esophageal and Gastric Varices/*CO/ET; Female; Gastrointestinal Hemorrhage/ET/*PC/PP; Heart Rate/DE; Hemodynamics/*DE; Human; Liver Cirrhosis/CO; Male; Middle Age; Propranolol/PD/*TU; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Venous Pressure/DE. .T Hemodynamic events in a prospective randomized trial of propranolol versus placebo in the prevention of a first variceal hemorrhage. .P CLINICAL TRIAL; JOURNAL ARTICLE. .W In a double-blind randomized trial, the hemodynamic events following the administration of propranolol (n = 51) or a placebo (n = 51) were prospectively studied in cirrhotic patients with esophageal varices. The hepatic venous pressure gradient, heart rate, and variceal size were determined at the baseline and 3, 12, and 24 months after the beginning of therapy. Baseline values were similar in both groups. At 3 months, the hepatic venous pressure gradient decreased significantly in propranolol-treated patients (from 18.1 +/- 4.2 to 15.7 +/- 3.4 mm Hg; P less than 0.05) but not in patients receiving the placebo (19.6 +/- 6.8 to 17.5 +/- 5.3 mm Hg; NS). At subsequent time intervals this gradient decreased significantly from the baseline value in both groups. Heart rate decreased significantly in the propranolol-treated group at all times (P less than 0.001). Variceal hemorrhage occurred in 13 patients (11 placebo-, 2 propranolol-treated; P less than 0.01), all of whom had a hepatic venous pressure gradient greater than 12 mm Hg. In 21 patients (14 propranolol-, 7 placebo-treated) the hepatic venous pressure gradient decreased to less than or equal to 12 mm Hg; none of them bled from esophageal varices, and their mortality rate also decreased. Because most of the bleeding events occurred during the first year (10 placebo-, 1 propranolol-treated; P less than 0.01), propranolol seems to have its protective effect during the period associated with the largest reduction in the hepatic venous pressure gradient. Because a reduction in the hepatic venous pressure gradient to less than 12 mm Hg protects from variceal bleeding and increases the rate of survival, this should be the aim of the pharmacological therapy of portal hypertension. .A Groszmann RJ; Bosch J; Grace ND; Conn HO; Garcia-Tsao G; Navasa M; Alberts J; Rodes J; Fischer R; Bermann M; et al. .I 275058 .U 91007094 .S Gastroenterology 9101; 99(5):1408-13 .M Alanine Aminotransferase/ME; Female; Human; Liver/EN; Liver Diseases/CO/EN/*PP; Liver Function Tests; Male; Obesity/*CO; Retrospective Studies; Weight Loss/*. .T Effect of weight reduction on hepatic abnormalities in overweight patients. .P JOURNAL ARTICLE. .W The effects of weight reduction on hepatic test results and physical findings related to the liver were retrospectively evaluated in 39 overweight patients screened to exclude other factors affecting the liver. An additional 11 overweight patients with primary liver disease were retrospectively evaluated to compare the effect of weight reduction in patients with liver disease with its effect in those without primary liver disease. This study showed that in overweight adults without primary liver disease, a weight reduction of greater than or equal to 10% corrected abnormal hepatic test results, decreased hepatosplenomegaly, and resolved some stigmata of liver disease. In similarly studied overweight patients with primary liver disease, some findings improved, but the changes did not correlate with a greater than or equal to 10% weight loss. Increased alanine aminotransferase activity was the most frequent hepatic enzyme abnormality in this population. For every 1% reduction in body weight, alanine aminotransferase activity improved by 8.1%. After other causes of liver disease are eliminated by clinical and biochemical parameters, weight reduction should be tried for overweight patients with abnormal hepatic test results in the absence of obvious primary liver disease as judged by clinical and biochemical parameters before extensive and expensive studies are undertaken. .A Palmer M; Schaffner F. .I 275059 .U 91007095 .S Gastroenterology 9101; 99(5):1414-20 .M Animal; Carcinoma/*PA; Colonic Neoplasms/PA; Female; Human; Pancreatic Neoplasms/PA; Rats; Stomach Neoplasms/*PA; Support, Non-U.S. Gov't; Trypsin Inhibitor, Kazal Pancreatic/*PD; Tumor Cells, Cultured; Vulvar Neoplasms/PA. .T Pancreatic secretory trypsin inhibitor stimulates the growth of rat pancreatic carcinoma cells. .P JOURNAL ARTICLE. .W Pancreatic secretory trypsin inhibitor was examined for growth-promoting activity on five cell lines using standard cell culture techniques. One cell line, AR4-2J, derived from a rat pancreatic acinar cell carcinoma, responded with significantly increased incorporation of [3H]thymidine and colony formation. Pancreatic secretory trypsin inhibitor stimulated the incorporation of [3H]thymidine in liquid culture; the maximal increase was 61 +/- 10% above control (P less than 0.001) and was seen at a concentration of 10(-9) mol/L. Using a soft agarose clonogenic assay, pancreatic secretory trypsin inhibitor also consistently stimulated (3 assays) colony formation: the peak activity occurred at a concentration of 10(-10) mol/L which caused a 150 +/- 55% (mean +/- SE, P less than 0.05) increase above control. Aprotinin had no effect on the growth of AR4-2J cells and pancreatic secretory trypsin inhibitor did not bind to the epidermal growth factor receptor. AR4-2J cells were shown to produce pancreatic secretory trypsin inhibitor. The study raises the possibility that pancreatic secretory trypsin inhibitor provides autocrine stimulation of tumor cell growth. .A Freeman TC; Curry BJ; Calam J; Woodburn JR. .I 275060 .U 91007096 .S Gastroenterology 9101; 99(5):1421-30 .M Adult; Aged; Aged, 80 and over; Amylases/BL; Calcium-Binding Proteins/*AN/BL; Chronic Disease; Female; Human; Immunoassay; Immunoblotting; Lipase/BL; Male; Middle Age; Pancreatic Diseases/BL/*ME; Pancreatic Juice/*CH; Pancreatic Neoplasms/ME; Pancreatitis/ME; Phosphoproteins/*AN/BL; Support, Non-U.S. Gov't. .T Immunochemical characterization and quantitative distribution of pancreatic stone protein in sera and pancreatic secretions in pancreatic disorders. .P JOURNAL ARTICLE. .W A fluorometric immunoassay has been established to quantitate pancreatic stone protein providing a sensitivity for concentrations from 0.015 to 0.5 micrograms/mL. When concentrations of pancreatic stone protein were determined from pancreatic secretions obtained either from patients suffering from chronic pancreatitis (n = 31) [including the calcifying forms (n = 10)], pancreatic cancer (n = 22), or nonpancreatic diseases (n = 17), no significant differences were found. In contrast, increased concentrations were found in serum samples from patients with chronic (39/66) and acute pancreatitis (16/20) compared with control patients. The differences between these diagnostic groups and controls were highly significant (P less than 0.0001) and independent of pancreatic enzyme activity. Immunochemical analyses of serum pancreatic stone protein showed an isoelectric point (pH 9) similar to that reported for the pancreatic thread protein. With respect to recent communications, these data do not support the etiopathogenic role postulated for pancreatic stone protein in chronic pancreatitis and chronic calcifying pancreatitis by other investigators. .A Schmiegel W; Burchert M; Kalthoff H; Roeder C; Butzow G; Grimm H; Kremer B; Soehendra N; Schreiber HW; Thiele HG; et al. .I 275061 .U 91007097 .S Gastroenterology 9101; 99(5):1431-8 .M Basement Membrane/ME; Bile Acids and Salts/*ME; Biological Transport, Active/DE; Female; Human; Hydrogen-Ion Concentration; Maternal-Fetal Exchange; Osmolar Concentration; Pregnancy; Support, Non-U.S. Gov't; Taurocholic Acid/*PK; Temperature; Time Factors; Trophoblast/*ME. .T Bile acid transport by basal membrane vesicles of human term placental trophoblast. .P JOURNAL ARTICLE. .W The aim of this work was to investigate the first step in the vectorial translocation of bile acids from the fetus to the mother, which is the transfer across the basal (i.e., fetal-facing) plasma membrane of the trophoblast. Thus, the uptake of [14C]taurocholate by basal plasma membrane vesicles obtained from normal human term placentas was studied. Taurocholate retention into vesicles was studied using a rapid filtration technique that was modified to reduce the taurocholate binding to the filters and to the external surface of the vesicles. Using 100 mumol/L substrate, the membrane vesicles showed a temperature-dependent, Na(+)-independent transport of taurocholate into an osmotically reactive intravesicular space. The initial rate of taurocholate influx in the presence of 100 mmol/L KNO3 followed saturation kinetics (apparent Km for taurocholate = 670 +/- 128 mumol/L; Vmax = 1.86 +/- 0.28 nmol/mg protein.60 s at 37 degrees C). Over the 6.9-7.9 pH range neither internal nor external pH nor inward nor outward proton gradients affected the uptake of taurocholate. When the electrical potential difference across the basal membrane was manipulated by external anion replacement (Cl-, SCN-, SO4(2-), or NO3-) or by valinomycin-induced K(+)-diffusion potential (vesicle inside negative), taurocholate uptake was not significantly modified. Taurocholate uptake was cis-inhibited in the presence of 1 mmol/L glycocholate, 0.5 mmol/L 4,4'-diisothiocyanostilbene-2,2'-disulfonate and 0.5 mmol/L sulfobromophthalein. However, 1 mmol/L probenecid or 0.5 mmol/L p-aminohippurate had no effect. Moreover, preloading the vesicles with 100 mmol/L HCO3- (but not with 100 mmol/L Cl- or 50 mmol/L SO4(2-) induced a significant enhancement in the initial rate of taurocholate uptake. In summary, these findings provide strong evidence for the presence of an electroneutral transport system for taurocholate in the basal plasma membrane of human chorionic trophoblast. They also suggest that this is likely to be an anion-exchange system. .A Marin JJ; Serrano MA; el-Mir MY; Eleno N; Boyd CA. .I 275062 .U 91007098 .S Gastroenterology 9101; 99(5):1439-44 .M Adult; Aged; Bile Acids and Salts/*TU; Chenodeoxycholic Acid/TU; Cholelithiasis/*TH; Combined Modality Therapy; Female; Follow-Up Studies; Human; Lithotripsy/IS/*MT; Male; Middle Age; Ursodeoxycholic Acid/TU. .T Piezoelectric lithotripsy: stone disintegration and follow-up results in patients with symptomatic gallbladder stones. .P JOURNAL ARTICLE. .W One hundred symptomatic patients with radiolucent gallbladder stones were treated with a new piezoelectric lithotripter and oral chemolitholytic agents. Stone disintegration was achieved in 99 of these patients (99%) with a mean (+/- SD) maximum fragment size of 5.1 +/- 4.1 mm. Significant differences were found when the mean (+/- SD) fragment sizes of single stones less than or equal to 20 mm (4.2 +/- 2.5 mm) were compared with those of single stones greater than 20 mm (5.8 +/- 3.4 mm; P less than 0.05) and multiple stones (6.2 +/- 3.8 mm; P less than 0.05), respectively. None of the patients required anesthesia, analgesics, or sedatives before or during the treatment. The stone-free rates for all patients followed up for up to 4-12 months (mean +/- SD, 10.7 +/- 2.9 months) were 18% (1 month), 25% (2 months), 38% (4 months), 52% (8 months), and 67% (12 months). Partly significant differences were obtained in stone-free rates for single stones (less than or equal to 20 mm) compared with larger stones (greater than 20 mm) and multiple stones (P less than 0.05), respectively. Serious adverse reactions (i.e., cholestasis and pancreatitis) were observed in only 3 patients (3%). These conditions were induced by fragment impaction in the common bile duct. In 2 of these patients, endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy was required. It is concluded that piezoelectrically generated shock waves are suitable for the effective and safe disintegration of gallbladder stones in humans. The anesthesia-free and analgesia-free shock-wave application opens up the possibility to perform biliary lithotripsy as an outpatient procedure. The stone-free rate achieved in combination with oral bile acids is most promising for single stones (less than or equal to 20 mm). .A Ell C; Kerzel W; Schneider HT; Benninger J; Wirtz P; Domschke W; Hahn EG. .I 275063 .U 91007099 .S Gastroenterology 9101; 99(5):1445-51 .M Analysis of Variance; Bile Acids and Salts/*SE; Calcium Carbonate/*ME; Common Bile Duct Calculi/*ME; Dose-Response Relationship, Drug; Human; Hydrogen-Ion Concentration; Regression Analysis; Secretin/*PD; Solubility/DE; Time Factors. .T The effects of synthetic human secretin on calcium carbonate solubility in human bile [see comments] .P JOURNAL ARTICLE. .W This study sought to determine the effects of synthetic human secretin on ionized calcium and carbonate concentrations in human hepatic bile. Five patients with a nasobiliary drain in the right hepatic duct were studied. Three basal samples of bile were collected, each over a 15-minute period. Synthetic human secretin was then infused IV at 0.05 micrograms.kg-1.h-1 for 45 minutes followed by 0.5 micrograms.kg-1.h-1 for 45 minutes. Bile was sampled over 15-minute periods. To document return to baseline conditions, two further samples of bile were obtained over 15-minute periods 2 hours after the infusion was terminated. Bile acid concentration was determined by an enzymatic method; pH and PCO2 were measured with an automated analyzer. Total calcium was determined by inductively coupled plasma emission spectrometry and ionized calcium by an ion-specific electrode. Bicarbonate and carbonate concentrations were calculated using Henry's law and the Henderson-Hasselbalch equation. The fraction of bile sampled by the catheter was determined by Indocyanin Green recovery at the end of the experiment. Secretin caused an increase in bile flow and bicarbonate output. Bicarbonate concentrations increased from 26 +/- 3 mmol/L to 41 +/- 3 mmol/L (P less than 0.05), and chloride concentrations decreased. Mean bile acid concentrations declined significantly from 14.6 +/- 2 mmol/L to 4.7 +/- 1 mmol/L (P less than 0.05). Ionized calcium concentrations decreased from 0.7 +/- 0.005 mmol/L to 0.5 +/- 0.02 mmol/L (P less than 0.05) while pH increased significantly from 7.44 +/- 0.06 to 7.6 +/- 0.04 (P less than 0.05). Carbonate concentrations increased significantly from 0.15 +/- 0.02 mmol/L to 0.26 +/- 0.03 mmol/L, and the ion product for calcium carbonate increased significantly from 0.099 +/- 0.002 (mmol/L)2 to 0.135 +/- 0.015 (mmol/L)2 (P less than 0.05). Synthetic human secretin augments the ion product of calcium and carbonate in human hepatic bile, increasing the tendency for calcium carbonate precipitation. .A Knyrim K; Vakil N. .I 275064 .U 91007100 .S Gastroenterology 9101; 99(5):1452-9 .M Analysis of Variance; Bile/*PH; Calcium/*ME; Cholesterol/ME; Fasting; Gallbladder/*PH; Human; Mucous Membrane/PH; Potassium/ME; Sodium/ME; Solubility; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Human gallbladder mucosal function. Effect of concentration and acidification of bile on cholesterol and calcium solubility. .P JOURNAL ARTICLE. .W The most recognized function of the human gallbladder is to store bile. However, this organ is not a static reservoir. It actively modifies bile by two processes: concentration and acidification. This study was designed to simultaneously evaluate the relationship between these two physiological processes in the normal human gallbladder and to define their effects on biliary cholesterol and calcium solubility. Bile was sampled directly from the gallbladder of 78 morbidly obese patients undergoing elective gastric bypass procedures. All had negative results of intra-operative ultrasound examinations for sludge and gallstones, normal liver function tests, and no history of hepatobiliary disease. Bile salt concentrations, an indirect index of concentration by the gallbladder, ranged from 15.1-272.8 mmol/L. As [bile salt] increased, [Na+], [K+], free [Ca2+], [cholesterol], [phospholipid], and [total lipid] increased linearly; [Cl-1] decreased linearly. Molar percent cholesterol decreased from 17.2% in dilute bile to 10.1% in fully concentrated bile, suggesting that cholesterol was absorbed by the gallbladder. As bile was concentrated, cholesterol saturation index decreased curvilinearly from a maximum of 3.7 in dilute bile to 1.0-1.5 in concentrated bile. Concentration of gallbladder bile was accompanied by progressive acidification. Bile pH decreased linearly with increasing [bile salt]; [CO3(2-)] decreased curvilinearly. Despite increasing [Ca2+], CaCO3 saturation index decreased curvilinearly with increasing [bile salt] from a maximum of 3.62 in dilute bile to a minimum of 0.12 in concentrated and acidified bile. CaCO3 saturation index also decreased exponentially with decreasing pH. This study concludes that concentration of bile enhances cholesterol solubility while acidification enhances calcium salt solubility. By increasing the solubilities of these two species, gallbladder mucosal function may play a key role in preventing gallstone formation. .A Shiffman ML; Sugerman HJ; Moore EW. .I 275065 .U 91007101 .S Gastroenterology 9101; 99(5):1460-6 .M Actins/ME/*PH; Animal; Cholesterol, Dietary/*AD; Contractile Proteins/PH; Gallbladder/ME/*PH; Male; Muscle Contraction/*; Muscle, Smooth/ME/PH; Myosin/ME/*PH; Sciuridae; Support, U.S. Gov't, P.H.S.. .T Actin and myosin isoforms in gallbladder smooth muscle following cholesterol feeding in prairie dogs. .P JOURNAL ARTICLE. .W Gallbladder smooth muscle contractility decreases after high-cholesterol feeding in prairie dogs. This decrease is not associated with alterations in the total amounts of the contractile proteins actin and myosin. The present study was designed to determine if cholesterol feeding results in alterations in the isoforms of actin and/or myosin heavy chain in gallbladder smooth muscle. Control prairie dogs were fed a trace-cholesterol diet and test animals were fed a high (1.2%)-cholesterol diet for 8 days. Although the proportion of beta-actin was unchanged, the proportion of alpha-actin in the gallbladder was less in the animals fed the high-cholesterol diet (32.6% +/- 1.5% in the control animals and 24.6% +/- 0.4% in the diet animals). On the other hand, the proportion of gamma-actin was significantly greater in the cholesterol-fed animals. There were no significant differences in the proportions of the myosin heavy-chain isoforms between the two groups. Also, there was no change in the volume fraction of smooth muscle in the gallbladders from the two groups. Thus, cholesterol feeding induces a shift in actin isoforms at the same time that there is a decrease in contractility. Whether the altered pattern of actin isoforms is related to the functional changes remains to be determined. .A Li YF; Bowers RL; Haley-Russell D; Moody FG; Weisbrodt NW. .I 275066 .U 91007102 .S Gastroenterology 9101; 99(5):1467-74 .M Animal; Cholelithiasis/*TH; Disease Models, Animal; Gallbladder/PH/PP; Lithotripsy/*MT; Liver/PH/PP; Lung/PH/PP; Pressure; Skin/PH/PP; Support, Non-U.S. Gov't; Swine. .T In vivo assessment of shock-wave pressures. Implication for biliary lithotripsy. .P JOURNAL ARTICLE. .W During extracorporeal shock-wave lithotripsy, the pressure profile, which is generated by the lithotriptor, determines the risk of tissue damage. In the present study, the pressure distribution of a lithotriptor (Lithostar; Siemens A.G., Erlangen, Federal Republic of Germany) was investigated in 10 pigs, five of which had gallstones surgically implanted into the gallbladder. The in vivo values were compared with in vitro data. Measurements were carried out along the shock-wave transmission path at the focus within the gallbladder, the adjacent liver, the diaphragmatic surface of the right lung, and the shock-wave exit site from the skin. Interposition of ribs did not cause a significant decrease in focal positive pressure. However, a gallstone positioned in the focus caused a 30%-65% reduction in pressure, recorded immediately behind the stone. Pressures obtained in vivo were always 15%-25% lower than those measured in vitro. The spatial distributions of the positive pressure in vivo and in vitro were almost identical. There was a high correlation between the pressures in vitro and in vivo (r = 0.88; P less than or equal to 0.01). This justifies assessment of shock-wave energies generated during biliary lithotripsy by extrapolation of in vitro data. It is concluded that it is possible to characterize different lithotriptors by in vitro pressure profile measurements. .A Vergunst H; Terpstra OT; Schroder FH; Matura E. .I 275067 .U 91007103 .S Gastroenterology 9101; 99(5):1475-9 .M Aged; Aged, 80 and over; Biliary Tract Neoplasms/*DI/RA; Cholangiopancreatography, Endoscopic Retrograde; Cytodiagnosis/IS/*MT; Female; Human; Male; Middle Age; Pancreatic Neoplasms/*DI/RA; Sensitivity and Specificity. .T Endoscopic retrograde brush cytology. A new technique. .P JOURNAL ARTICLE. .W Endoscopic retrograde cholangiopancreatography has been shown to be a very valuable adjunct in the diagnosis of malignancy involving the biliary and/or pancreatic ductal system. However, characteristic endoscopic retrograde cholangiopancreatography radiographic findings associated with malignant strictures are frequently not specific and cytological confirmation becomes essential for the diagnosis. Unfortunately, the current overall diagnostic yield of positive cytology in such circumstances ranges from 18%-56% depending on the technique. A new brush device has been designed which is uniquely adapted to pancreaticobiliary strictures of varying anatomical configurations. This study shows results using this new cytology brush in a series of 53 patients with pancreaticobiliary malignancy. A significant improvement in the cytological yield of tumor confirmation was obtained with a diagnostic sensitivity of 70% and specificity of 100% using the new brush technique. .A Venu RP; Geenen JE; Kini M; Hogan WJ; Payne M; Johnson GK; Schmalz MJ. .I 275068 .U 91007104 .S Gastroenterology 9101; 99(5):1480-4 .M Bile Duct Diseases/SU/US; Cholecystectomy/*; Common Bile Duct/*US; Dietary Fats/*DU; Fasting; Follow-Up Studies; Hepatic Duct, Common/*US; Human; Prospective Studies. .T Bile duct emptying in response to fat: a validation study. .P JOURNAL ARTICLE. .W Fatty meal sonography has been suggested to assess patients with biliary pain after cholecystectomy, but the effects of gallbladder removal on biliary dynamics has not been studied prospectively. Before elective cholecystectomy, 25 patients had their common hepatic ducts' diameter measured by ultrasonography before and after a fat stimulus. In 23, tests were repeated 1 month, 1 year, and 5 years after surgery. In preoperative studies, 5 patients showed dilatation after fat and 2 of these had stones in the common bile duct. However, another 4 patients with stones or sludge in the duct did not show dilatation, so that the response to fat was a poor indicator of patients requiring common bile duct exploration. No patient had major symptoms after surgery. At 1 month and 12 months, the response to fat was variable with more than half of those tested showing no decrease in duct size. A more consistent pattern emerged at 5 years, when 14 of 18 patients tested showed a decrease in common hepatic duct after fat; 3 were unchanged and 1 increased by 1 mm. The response to fat was less consistent and more difficult to measure in the common bile duct, even 5 years after operation. It was concluded that not all patients with indications for exploration of the common bile duct on operative cholangiography show a dilatation response to fat on preoperative testing. Also, fatty meal sonography should be used with caution because the response to fat in asymptomatic patients soon after operation is unpredictable, with occasional patients showing dilation without apparent obstruction. Measurement of common hepatic duct is preferred to common bile duct and increases in diameter of 1 mm are probably not significant. .A Hunt DR; Scott AJ. .I 275069 .U 91007105 .S Gastroenterology 9101; 99(5):1485-92 .M Ampicillin/*PD; Animal; Anions/*PD; Bile Acids and Salts/*SE; Cholesterol/*SE; Comparative Study; Hyperbilirubinemia, Hereditary/PP; Indocyanine Green/*PD; Male; Phospholipids/*SE; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't; Taurolithocholic Acid/*PD. .T The uncoupling of biliary lipid from bile acid secretion by organic anions in the rat. .P JOURNAL ARTICLE. .W A number of organic anions has been shown to inhibit biliary phospholipid and cholesterol secretion without affecting bile acid secretion. However, the mechanism of this uncoupling phenomenon is still unclear. This study shows a comparison of the effects of ampicillin (18 mumol/100g body wt), sulfated taurolithocholic acid (0.2 and 1.0 mumol/100 g body wt), and indocyanine green (0.6 mumol/100 g body wt) in control and Groningen Yellow-Wistar rats with chronic (8 days) biliary drainage. Groningen Yellow rats have a hereditary defect in hepatobiliary transport of various organic anions. Bile secretion, but not hepatic uptake, of the three organic anions was strongly impaired in Groningen Yellow rats compared with controls. Ampicillin and sulfated taurolithocholic acid caused a strong uncoupling in control rats but had no effect or a much smaller effect on lipid secretion in Groningen Yellow rats. Indocyanine green did not affect lipid secretion, in either control or in Groningen Yellow rats. Gel-filtration chromatography of bile showed a specific coelution of ampicillin and sulfated taurolithocholic acid with the bile acid fraction, whereas indocyanine green coeluted with the phospholipid/cholesterol fraction. This study concludes that the uncoupling by ampicillin and sulfated taurolithocholic acid occurs after their secretion into bile and is caused by interaction of these compounds with bile acids. It is hypothesized that this interaction inhibits the capacity of bile acids to induce secretion of phospholipids and cholesterol into the bile. .A Verkade HJ; Wolbers MJ; Havinga R; Uges DR; Vonk RJ; Kuipers F. .I 275070 .U 91007106 .S Gastroenterology 9101; 99(5):1493-501 .M Amino Acid Sequence; Animal; Cattle; Chromatography, High Pressure Liquid; Electrophoresis, Polyacrylamide Gel; Glycolysis; Immunologic Techniques; Molecular Sequence Data; Mucins/*CH/IP; Peptides/CH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Time Factors; Trypsin. .T Characterization of bovine gallbladder mucin. Amino acid sequences of tryptic peptides from the glycosylated domain of the protein core. .P JOURNAL ARTICLE. .W Gallbladder mucin is a densely glycosylated macro-molecule that promotes cholesterol gallstone formation in experimental animals and in humans. Bovine gallbladder mucin structure was studied after chemical deglycosylation by treatment with anhydrous hydrogen fluoride at 23 degrees C for 3 hours. Deglycosylated mucin contained less than 5% of the amino sugar and neutral hexose content of native mucin. Electrophoretic and molecular sieve chromatographic analyses indicated that significant cleavage of the mucin polypeptide core had occurred during deglycosylation. Deglycosylated mucin was separated into three major fractions by reverse-phase chromatography, one of which was enriched with respect to threonine and proline. Tryptic peptides prepared from this fraction were purified by molecular sieve and reverse-phase chromatography, and the amino acid sequences (8-20 residues) of the four principal tryptic peptides were determined. These peptides contained 65%-75% threonine and proline residues and demonstrated 80%-100% sequence similarity. These data provide the first information on the primary structure of gallbladder mucin and suggest that repeating amino acid sequences occur in this protein. Comparison of gallbladder mucin peptide structure with the consensus repeat sequence of human intestinal mucin showed approximately 60% sequence similarity. It was concluded that mammalian gastrointestinal mucins may be derived from a common ancestral gene. .A Afdhal NH; Offner GD; Smith BF. .I 275071 .U 91007107 .S Gastroenterology 9101; 99(5):1502-6 .M Adenoma/BS/PA/*TH; Aged; Ascites/TH; Case Report; Constriction, Pathologic/TH; Edema/TH; Embolization, Therapeutic/*; Human; Liver Neoplasms/BS/PA/*TH; Male; Pruritus/TH; Syndrome; Vena Cava, Inferior/*PA. .T Resolution of inferior vena cava syndrome after embolization of a hepatic adenoma. .P JOURNAL ARTICLE. .W A 77-year-old man presented with severe pruritus and massive lower body edema. Computerized axial tomography of the abdomen showed a large hepatic mass compressing the inferior vena cava, and a liver biopsy specimen showed hepatic adenoma. Embolization of vessels feeding the hepatic tumor resulted in complete resolution of pruritus and ascites, and clinical remission has persisted for 1 year following partial obliteration of tumor vasculature. Angiographic ablation of tumor blood supply represents a nonoperative means for inducing clinical remission in patients with symptomatic hepatic adenoma who are at high surgical risk. .A Meirowitz RF; Tobin KD; Elias EG; Iseri O; Pais SO; Knodell RG. .I 275072 .U 91007108 .S Gastroenterology 9101; 99(5):1507-10 .M Aged; Arteriovenous Malformations/*RA/SU; Case Report; Female; Gastrectomy; Human; Stomach/*BS/SU. .T Caliber-persistent artery of the stomach (Dieulafoy's vascular malformation). .P JOURNAL ARTICLE. .W Caliber-persistent artery of the stomach (also known as cirsoid aneurysm, Dieulafoy's lesion, and submucosal arterial malformation) is clinically manifested as recurrent, massive, often fatal hematemesis. The lesion often is not seen endoscopically. Left gastric angiography in one patient with hematemesis showed a convoluted and ectatic artery in the gastric fundus, which proved to be caliber-persistent artery of the stomach on pathological examination. The tortuosity of the abnormal vessel in this condition has been attributed to artefactual contraction of the stomach following excision and formalin fixation. This is the first reported case in which a pathologically proven lesion has been clearly visualized by angiography. This demonstrates that the submucosal vessel is truly and not artifactually sinuous. It is proposed that angiographic demonstration of a nontapering, convoluted artery in the territory of the left gastric artery is highly suggestive of caliber-persistent artery of the stomach. .A Eidus LB; Rasuli P; Manion D; Heringer R. .I 275073 .U 91007109 .S Gastroenterology 9101; 99(5):1511-3 .M Case Report; Diagnostic Errors; Endoscopy, Gastrointestinal; Gastrins/*BL; Human; Hyperlipidemia/*CO; Male; Middle Age; Zollinger-Ellison Syndrome/CO/*DI. .T Misdiagnosis of the Zollinger-Ellison syndrome due to hyperlipidemia. .P JOURNAL ARTICLE. .W Most authorities feel that diagnosis of the Zollinger-Ellison syndrome is established when the serum gastrin level is greater than 1000 pg/mL (1000 ng/L) in a patient with gastric acid hypersecretion and clinical manifestations consistent with the diagnosis. A patient with recurrent peptic ulcer disease is reported who was thought to have had the Zollinger-Ellison syndrome based on two serum gastrin level measurements greater than 1000 pg/mL (1000 ng/L). Subsequent evaluation revealed the gastrin elevation to be spurious because the sample was hyperlipidemic. Lipemic serum samples may yield falsely elevated serum gastrin determinations as determined by radioimmunoassay. .A Romeo DP; Weesner RE; Giannella RA. .I 275074 .U 91007110 .S Gastroenterology 9101; 99(5):1514-6 .M Bile Ducts/*PA; Case Report; Hepatoma/*PA; Human; Hyperplasia; Liver Neoplasms/*PA; Male; Middle Age; Neoplasm Recurrence, Local/*PA; Syndrome. .T Late recurrence of a hepatocellular carcinoma in a patient with incomplete Alagille syndrome. .P JOURNAL ARTICLE. .W In this study, the case of a patient presenting a second hepatocellular carcinoma 13 years after resection of a first tumor of the same type is reported. In this case, etiological investigations remained negative, but an incomplete form of syndromatic Alagille syndrome with paucity of bile ducts in the nontumoral tissue was detected and associated with nodular regenerative hyperplasia and foci of dysplasia. Malignant transformation in Alagille syndrome seems to be extremely rare. The fact that such tumors evolve very slowly could be an argument for partial hepatectomy and, if necessary, liver transplantation. .A Le Bail B; Bioulac-Sage P; Arnoux R; Perissat J; Saric J; Balabaud C. .I 275075 .U 91007111 .S Gastroenterology 9101; 99(5):1517-9 .M Adolescence; Adult; Aminotransferases/BL; Case Report; Child; Child, Preschool; Human; Liver Diseases/*CI/EN; Male; Middle Age; Pemoline/AD/*AE. .T Pemoline-associated hepatic injury. .P JOURNAL ARTICLE. .W Among 100 cases of hepatic injury attributed to the administration of pemoline, 43 had sufficient accompanying information to permit analysis. All but two patients were less than 20 years old, and 80% were less than 12 years old. Males predominated the study. Injury appeared as early as 1 week or as late as greater than 1 year of taking the drug. The injury was uniformly hepatocellular as judged by the high values for aminotransferases and by death in massive necrosis in one patient. Mechanism was judged to be idiosyncratic, and the idiosyncrasy was probably metabolic rather than immunologic. .A Nehra A; Mullick F; Ishak KG; Zimmerman HJ. .I 275076 .U 91007112 .S Gastroenterology 9101; 99(5):1520-1 .M Amylases/BL; Ascites/BL/*DT/ET; Case Report; Human; Infusions, Intravenous; Male; Middle Age; Octreotide/AD/*TU; Pancreatic Diseases/BL/*CO; Serum Albumin/ME. .T Somatostatin in the treatment of pancreatic ascites [see comments] .P JOURNAL ARTICLE. .A Oktedalen O; Nygaard K; Osnes M. .I 275077 .U 91007113 .S Gastroenterology 9101; 99(5):1522-3 .M Human; Internal Medicine/*; National Institutes of Health (U.S.)/*; Research Support/*; United States. .T Reports from the NIH DDDN. The General Medicine A-2 Study Section. .P JOURNAL ARTICLE. .A Kalser SC; Khan MA. .I 275078 .U 91007114 .S Gastroenterology 9101; 99(5):1524-6 .M Esophageal and Gastric Varices/*CO; Gastrointestinal Hemorrhage/*DT/ET; Human; Somatostatin/AD/*TU. .T Somatostatin for variceal bleeders [editorial] .P EDITORIAL. .A Resnick RH. .I 275079 .U 91007115 .S Gastroenterology 9101; 99(5):1527-9 .M Adult; Cholangiopancreatography, Endoscopic Retrograde; Cholecystectomy/EC/*MT; Cholelithiasis/DT/*SU/TH; Human; Laser Surgery; Length of Stay; Peritoneoscopy/EC. .T Laparoscopic cholecystectomy: passing fancy or legitimate treatment option? .P JOURNAL ARTICLE. .A Miller TA. .I 275080 .U 91007116 .S Gastroenterology 9101; 99(5):1529-30 .M Acute Disease; Aged; Cholecystitis/*/CO/DI/EP/SU; Female; Human; Male; Middle Age; Outpatients; Predictive Value of Tests; Prevalence; Retrospective Studies. .T Acalculous cholecystitis: a new perspective. .P JOURNAL ARTICLE. .A Malet PF. .I 275081 .U 91007117 .S Gastroenterology 9101; 99(5):1530-1 .M Acute Disease; Cholangitis/SU/*TH; Combined Modality Therapy; Drainage/MT; Emergencies; Endoscopy; Human; Retrospective Studies. .T Acute cholangitis--endoscopic drainage or emergency surgery? .P JOURNAL ARTICLE. .A Magun A. .I 275082 .U 91007118 .S Gastroenterology 9101; 99(5):1531-3 .M Antibodies, Viral/*BL; Autoimmune Diseases/*IM; Enzyme-Linked Immunosorbent Assay; Female; Hepatitis C Virus/*IM; Hepatitis, Chronic Active/DI/*IM; Human; IgG/AN; Male; Predictive Value of Tests. .T Implications of anti-hepatitis C reactivity in 'autoimmune' chronic active hepatitis. .P JOURNAL ARTICLE. .A Thiele DL. .I 275083 .U 91007120 .S Gastroenterology 9101; 99(5):1538 .M Colonic Diseases, Functional/*DH/PP; Dietary Fiber/*TU; Gastrointestinal Motility/*; Human; Rectum/*PP; Sigmoid/*PP. .T Effect of dietary fiber on symptoms and rectosigmoid motility in patients with irritable bowel syndrome [letter; comment] .P COMMENT; LETTER. .A van Steensel CJ. .I 275084 .U 91007121 .S Gastroenterology 9101; 99(5):1538-40 .M Bacterial Infections/*DI; Diagnosis, Differential; Human; Liver Cirrhosis/*CO; Peritonitis/*DI. .T Differentiation of spontaneous from secondary bacterial peritonitis in cirrhotics [letter; comment] .P COMMENT; LETTER. .A Gomez-Jimenez J; Ribera E; Gasser I; Pahissa A; Martinez-Vazquez JM. .I 275085 .U 91007122 .S Gastroenterology 9101; 99(5):1540 .M Analysis of Variance; Double-Blind Method; Famotidine/*PD; Heart/PP; Hemodynamics/*DE; Human; Prospective Studies. .T Hemodynamic status during famotidine infusion [letter; comment] .P COMMENT; LETTER. .A Heiselman DE; Malik M; White LJ. .I 275086 .U 91007123 .S Gastroenterology 9101; 99(5):1540-1 .M Human; Japan/EP; New York/EP; Stomach Neoplasms/*EP; Survival Rate. .T Geopathology of early gastric cancer [letter; comment] .P COMMENT; LETTER. .A Green PH; O'Toole KM; Slonim D. .I 275087 .U 91007125 .S Gastroenterology 9101; 99(5):1542-3 .M Gastric Acid/*SE; Gastric Acidity Determination; Gastroesophageal Reflux/DT/*ET; Human; Omeprazole/TU. .T Is gastric acid hypersecretion the only reason for refractory gastroesophageal reflux disease? [letter; comment] .P COMMENT; LETTER. .A Savarino V; Mela GS; Zentilin P; Celle G. .I 275088 .U 91007127 .S Gastroenterology 9101; 99(5):1544-6 .M Acute Disease; Alcoholism/*CO; Human; Necrosis; Pancreatitis/*ET/PA. .T Can alcohol cause true acute pancreatitis? [letter; comment] .P COMMENT; LETTER. .A Blackstone MO. .I 275089 .U 91007128 .S Gastroenterology 9101; 99(5):1547 .M Breath Tests/*; Human; Intestines/*MI; Lactulose/*DU; Predictive Value of Tests; Sensitivity and Specificity. .T Lactulose hydrogen breath test in the diagnosis of bacterial overgrowth [letter; comment] .P COMMENT; LETTER. .A Rhodes JM; Jewell DP. .I 275090 .U 91007129 .S Gastrointest Endosc 9101; 36(4):331-6 .M Abscess/ET/*US; Adult; Anus/PA; Colonic Diseases/ET/*US; Crohn Disease/CO/*US; Female; Human; Intestinal Fistula/ET/*US; Male; Rectal Fistula/ET/*US; Rectum/PA. .T Endosonography of peri-anal and peri-colorectal fistula and/or abscess in Crohn's disease. .P JOURNAL ARTICLE. .W Transcolorectal endosonography (ES) was performed in 36 patients with Crohn's disease suspected clinically to have a fistula or abscess. A hypoechoic or anechoic duct-like lesion immediately adjacent to the anorectal lumen compatible with a fistula was found in 32 patients. A communication between the fistulous tract and adjacent structures such as the skin, anal canal, or vagina was detected in all 32 patients. An anechoic cavity adjacent to or communicating with the fistula was visualized in 29 of the 36 patients. A fistula was visualized in the remaining seven patients with no evidence of an abscess. This anechoic cavity compatible with an abscess was surgically confirmed in 14 of 17 patients. We judged the extent and configuration of the abnormalities to be more clearly visualized by ES when results were compared with fistulography in five patients. There were no ES complications, and we conclude that ES is the preferred diagnostic procedure in patients with peri-rectal pathology because of the low risk of bacterial dissemination and low incidence of patient discomfort. Utilizing ES after non-surgical treatment was successful in 19 patients for documentation of the response to therapy. .A Tio TL; Mulder CJ; Wijers OB; Sars PR; Tytgat GN. .I 275091 .U 91007130 .S Gastrointest Endosc 9101; 36(4):337-41 .M Arteriovenous Malformations/*CO/DI; Colonoscopy/*IS; Duodenum/BS; Endoscopy, Gastrointestinal/*MT; Gastrointestinal Hemorrhage/*ET; Human; Jejunum/BS; Middle Age. .T Push-enteroscopy for diagnosis of patients with gastrointestinal bleeding of obscure origin. .P JOURNAL ARTICLE. .W Push-enteroscopy using a disinfected colonoscope was performed on 39 patients with gastrointestinal bleeding of obscure origin. Our results show that: (1) A high percentage of patients (38%) have pathological lesions responsible for bleeding located in the distal duodenum and proximal jejunum, which are readily detected by push-enteroscopy. (2) Duodeno-jejunal arteriovenous malformations (AVMs) are the most common cause for bleeding, and these lesions can be conveniently cauterized through the endoscope. (3) An efficient sequence of steps for diagnosis of patients with this problem includes push-enteroscopy when the initial EGD and colonoscopy are normal followed by small bowel radiography. Mesenteric angiography and intraoperative enteroscopy can be reserved for patients with severe bleeding when push-enteroscopy and small bowel radiography are negative. We conclude that push-enteroscopy has an important role to play in the early assessment of patients with gastrointestinal bleeding of obscure origin. .A Foutch PG; Sawyer R; Sanowski RA. .I 275092 .U 91007131 .S Gastrointest Endosc 9101; 36(4):342-50 .M Barium Sulfate/DU; Comparative Study; Endoscopy, Gastrointestinal/MT; Esophageal Neoplasms/RA/*US; Human; Leiomyoma/RA/*US; Leiomyosarcoma/RA/*US; Stomach Neoplasms/RA/*US; Tomography, X-Ray Computed. .T Endoscopic ultrasonography for the evaluation of smooth muscle tumors in the upper gastrointestinal tract: an experience with 42 cases. .P JOURNAL ARTICLE. .W Before surgery, 12 patients with suspected leiomyoma and 12 patients with suspected leiomyosarcoma were studied by endoscopic ultrasonography (EUS), computed tomography (CT), endoscopy, and barium swallow. The results were correlated with surgery and histology. Ten leiomyomas, one benign gastric ulcer, one carcinoid metastasis, eight leiomyosarcomas, two leiomyoblastomas, one mucus secreting adenocarcinoma, and one bronchial carcinoma were diagnosed. Eighteen additional patients suspected to have benign submucosal lesions by endoscopy and barium meal were treated non-surgically, and studied by EUS and CT. EUS was superior to other imaging techniques in the detection, staging, and follow-up of submucosal smooth muscle tumors because of clear imaging of the intramural abnormality and adjacent lymph nodes. .A Tio TL; Tytgat GN; den Hartog Jager FC. .I 275093 .U 91007132 .S Gastrointest Endosc 9101; 36(4):351-6 .M Common Bile Duct Calculi/*TH; Human; Lithotripsy/*IS/MT. .T Mechanical lithotripsy of common duct stones. .P JOURNAL ARTICLE. .W Over the past 8 years we have utilized various types of mechanical lithotriptors to crush common bile duct stones. The procedure was performed in 93 patients with an overall success rate of 94%. However, because many accessories were in a developmental stage, entrapment of stones was not always possible on the first attempt, and the procedure was repeated in some patients a second or third time. During the interim, while awaiting another attempt at lithotripsy, cholangitis was prevented by leaving a prosthesis in place. A variety of lithotriptor models from different manufacturers have proven effective. We recommend that endoscopists use these devices to rid the bile duct of retained stones. .A Siegel JH; Ben-Zvi JS; Pullano WE. .I 275094 .U 91007133 .S Gastrointest Endosc 9101; 36(4):357-9 .M Bronchial Fistula/ET/*TH; Carcinoma, Non-Small Cell Lung/*CO; Esophageal Fistula/ET/*TH; Esophageal Stenosis/ET/*TH; Esophagoscopy; Female; Human; Intubation/*MT; Lung Neoplasms/*CO; Male; Middle Age; Palliative Treatment/*MT. .T Endoscopic palliative intubation of the esophagus invaded by lung cancer. .P JOURNAL ARTICLE. .W Thirty-two patients with esophageal involvement by lung cancer were managed by endoscopic intubation. In 22 patients with extrinsic esophageal strictures, the success rate of intubation was 91%, and 82% were discharged with their dysphagia relieved and esophageal patency restored. The mean survival rate was 4.4 months. In 10 patients with esophago-bronchial fistulas, 3 had the fistulous tract obliterated and lived a mean of 5 months. This low success rate of closing fistulas is due to failure to seal off the space between the stent and the fistula because of absence of tumor-associated stenosis. The overall morbidity rate was 28.1% (18.8% perforation, 6.3% hemorrhage, and 3.1% tracheal obstruction). The overall mortality rate was 18.8%. Although complications were more frequent than in primary esophageal tumors, endoscopic intubation was the only way to palliate this desperate condition and provided 66.6% of patients with relief of symptoms, nutritional improvement, and a mean survival time of 4.5 months. .A Buset M; Des Marez B; Cremer M. .I 275095 .U 91007134 .S Gastrointest Endosc 9101; 36(4):360-3 .M Bile Ducts/PA; Cholangiopancreatography, Endoscopic Retrograde; Clonorchiasis/DT/*RA; Female; Follow-Up Studies; Human; Liver Diseases, Parasitic/DT/PS/*RA; Male; Middle Age; Praziquantel/TU; Support, Non-U.S. Gov't; Time Factors. .T Endoscopic cholangiopancreatography in hepatic clonorchiasis--a follow-up study. .P JOURNAL ARTICLE. .W Cholangiographic changes of the biliary system in 16 patients with proven hepatic clonorchiasis, diagnosed by positive stool or bile ova isolates, were studied. All patients presented with epigastric pain. Other symptoms included jaundice in 31% (5 of 16) and fever in 12.5% (2 of 16). Praziquantel given at 25 mg/kg for three doses in 1 day were administered. Three consecutive stool tests were performed 3 months after treatment and were negative in 87.5% (14 of 16). ERCP studies were repeated at a mean interval of 31.6 months (range, 8 to 69 months). Measurements of the bile ducts on retrograde cholangiograms before and after treatment were compared using the paired Student's t test. Filling defects and blunting of the terminal bile ducts seen on the initial cholangiogram, interpreted as the presence of adult worms, disappeared after treatment. However, there was no significant change between pre- and post-treatment measurement of bile duct caliber. Bile duct dilation, irregularities, and ductal proliferation persisted despite eradication of the parasite. .A Leung JW; Sung JY; Banez VP; Wu ZM; Agas FV Jr; Ling TK; Chung SC. .I 275096 .U 91007136 .S Gastrointest Endosc 9101; 36(4):369-72 .M Abdominal Pain/*RA; Adolescence; Biliary Tract Diseases/*RA; Case Report; Child; Child, Preschool; Cholangiopancreatography, Endoscopic Retrograde/*; Female; Human; Male; Pancreatic Diseases/*RA. .T The role of ERCP in children and adolescents. .P JOURNAL ARTICLE. .W The diagnostic and therapeutic role of ERCP in 42 patients ranging from 1 to 19 years of age is discussed. ERCP provided useful additional information in 15 patients with biliary tract disease, 15 patients with pancreatic disease, and 9 patients with abdominal pain. The appropriate duct was cannulated in 95% of cases. Mild pancreatitis occurred in two patients after ERCP. Endoscopic papillotomy was successful in five patients. ERCP plays an important part in the investigation of unexplained biliary tract and pancreatic disease. It rarely demonstrates abnormal pathology in patients with otherwise unexplained abdominal pain. .A Buckley A; Connon JJ. .I 275097 .U 91007137 .S Gastrointest Endosc 9101; 36(4):373-5 .M Aged; Dilatation; Esophageal Stenosis/*TH; Fluoroscopy/*; Human; Judgment. .T Can clinicians accurately assess esophageal dilation without fluoroscopy? .P JOURNAL ARTICLE. .W This study questioned whether clinicians could determine the success of esophageal dilation accurately without the aid of fluoroscopy. Twenty patients were enrolled with the diagnosis of distal esophageal stenosis, including benign peptic stricture (17), Schatski's ring (2), and squamous cell carcinoma of the esophagus (1). Dilation attempts using only Maloney dilators were monitored fluoroscopically by the principle investigator, the physician and patient being unaware of the findings. Physicians then predicted whether or not their dilations were successful, and they examined various features to determine their usefulness in predicting successful dilation. They were able to predict successful dilation accurately in 97% of the cases studied; however, their predictions of unsuccessful dilation were correct only 60% of the time. Features helpful in predicting passage included easy passage of the dilator (98%) and the patient feeling the dilator in the stomach (95%). Excessive resistance suggesting unsuccessful passage was an unreliable feature and was often due to the dilator curling in the stomach. When Maloney dilators are used to dilate simple distal strictures, if the physician predicts successful passage, he is reliably accurate without the use of fluoroscopy; however, if unsuccessful passage is suspected, fluoroscopy must be used for confirmation. .A Bailey AD; Goldner F. .I 275098 .U 91007138 .S Gastrointest Endosc 9101; 36(4):376-8 .M Duodenal Diseases/*DI; Duodenum/*PA; Endoscopy, Gastrointestinal; Female; Human; Intestinal Mucosa/PA; Lymphangiectasis, Intestinal/*DI; Male; Middle Age. .T Endoscopic appearance and significance of functional lymphangiectasia of the duodenal mucosa. .P JOURNAL ARTICLE. .W Intestinal lymphangiectasia is found in a wide variety of pathologic conditions. Functional lymphangiectasia has not been well characterized. We report 20 patients followed for 9 to 55 months (mean 30 months) after incidental detection at endoscopy of lymphangiectasia. Our study indicates that functional lymphangiectasia is not pathologic and does not warrant repeat endoscopy in the absence of other clinical indications. .A Patel AS; DeRidder PH. .I 275099 .U 91007139 .S Gastrointest Endosc 9101; 36(4):379-81 .M Biopsy/*IS; Comparative Study; Disposable Equipment/*; Endoscopy, Gastrointestinal/*IS; Equipment Contamination/PC; Human; Plastics; Specimen Handling/IS. .T Adequacy of disposable biopsy forceps for gastrointestinal endoscopy: a direct comparison with reusable forceps. .P CLINICAL TRIAL; JOURNAL ARTICLE. .W Disposable plastic biopsy forceps were compared prospectively to reusable stainless steel forceps. Thirty consecutive patients underwent a total of 249 biopsies, 124 with the disposable forceps, and 125 with reusable forceps. Biopsy locations included the esophagus, stomach, small intestine, colon, and common bile duct. Specimens were compared microscopically to determine overall surface area, depth, adequacy, and diagnostic result. The disposable biopsy forceps yielded specimens which were 37% smaller when compared with the reusable forceps. In five of the comparisons, minor differences in histological findings were noted between the two groups of biopsy specimens, but these differences did not alter the pathological diagnosis. However, in three cases in which superficial specimens were obtained, an underlying carcinoma was missed with the disposable forceps. Our study documents the utility of disposable biopsy forceps for mucosal lesions. In addition, there were 11 mechanical failures in 38 biopsy attempts with the plastic biopsy forceps. These forceps appear to be limited in their capacity to obtain adequate specimens from firm tissue or when submucosal biopsy samples are required, and they will require refinements in design to duplicate specimen quality obtained by traditional reusable forceps. Disposable forceps are particularly suitable for biopsy of mucosal lesions in patients with possible communicable disease, and they should help to reduce cross-contamination in the gastroenterology laboratory. .A Yang R; Vuitch F; Wright K; McCarthy J. .I 275100 .U 91007140 .S Gastrointest Endosc 9101; 36(4):382-6 .M Adenoma/US; Colonic Neoplasms/*US; Colonoscopy/*IS; Colorectal Neoplasms/*US; Crohn Disease/*US; Female; Human; Male; Ultrasonography/IS. .T Colonic endoscopic ultrasonography: first results of a new technique. .P JOURNAL ARTICLE. .A Rosch T; Lorenz R; Suchy R; Dancygier H; Classen M. .I 275101 .U 91007141 .S Gastrointest Endosc 9101; 36(4):386-9 .M Biliary Tract/*; Catheterization/*IS; Cholangiopancreatography, Endoscopic Retrograde; Cystic Duct/*; Equipment Design; Gallbladder/*; Human; Radiology, Interventional/IS. .T Cannulation of the biliary tree, cystic duct and gallbladder using a hydrophilic polymer-coated steerable guide wire. .P JOURNAL ARTICLE. .A McCarthy JH; Miller GL; Laurence BH. .I 275102 .U 91007143 .S Gastrointest Endosc 9101; 36(4):392-4 .M Color; Endoscopy, Gastrointestinal/*IS; Fluoroscopy/*IS; Human; Photography/IS; Video Recording/*IS. .T Documentation of fluoroscopic and endoscopic images using a color video printer. .P JOURNAL ARTICLE. .A Stroehlein JR; Barroso A; Glombicki A; Sachs I. .I 275103 .U 91007144 .S Gastrointest Endosc 9101; 36(4):394-7 .M Acquired Immunodeficiency Syndrome/*CO; Adult; Bronchial Fistula/CO; Case Report; Esophageal Fistula/*CO/DI; Esophagoscopy; Human; Male; Mycobacterium avium-intracellulare Infection/*CO; Tuberculosis, Pulmonary/*CO. .T Inflammatory double-barrelled esophagus in two patients with AIDS. .P JOURNAL ARTICLE. .A Stoopack PM; de Silva R; Raufman JP. .I 275104 .U 91007145 .S Gastrointest Endosc 9101; 36(4):397-9 .M Case Report; Diagnosis, Differential; Esophageal Diseases/*DI; Esophageal Neoplasms/DI; Esophagoscopy; Esophagus/*PA; Female; Human; Leukoplakia/*DI; Middle Age; Parakeratosis/*DI. .T Compact parakeratosis of esophageal mucosa: a non-specific lesion mimicking "leukoplakia". .P JOURNAL ARTICLE. .A Lam TS; Lack E; Benjamin SB. .I 275105 .U 91007146 .S Gastrointest Endosc 9101; 36(4):399-402 .M Arteriovenous Malformations/*SU; Case Report; Electrocoagulation/*; Female; Human; Middle Age; Pyloric Antrum/BS; Stomach Diseases/*SU. .T Bipolar electrocoagulation for watermelon stomach. .P JOURNAL ARTICLE. .A Binmoeller KF; Katon RM. .I 275106 .U 91007147 .S Gastrointest Endosc 9101; 36(4):402-4 .M Aged; Bile Ducts, Intrahepatic/*; Case Report; Cholelithiasis/*TH; Common Bile Duct; Human; Lithotripsy/*IS/MT; Male. .T Removal of intrahepatic stone by rigid ultrasonic lithotripter through a choledochotomy tract. .P JOURNAL ARTICLE. .A Ng SK; Yip WC; Chow WC; Choi TK. .I 275107 .U 91007148 .S Gastrointest Endosc 9101; 36(4):404-6 .M Aged; Case Report; Diagnosis, Differential; Esophageal Stenosis/*DI; Esophagoscopy; Human; Larynx, Artificial/*; Male; Prosthesis Design. .T Endoscopic diagnosis of the Panje prosthesis in a patient with upper esophageal stricture. .P JOURNAL ARTICLE. .A Mai H; Sanowski RA. .I 275108 .U 91007149 .S Gastrointest Endosc 9101; 36(4):406-8 .M Aged; Case Report; Esophagoscopy; Female; Foreign Bodies/*TH; Gastroscopy; Human; Pyloric Antrum/*. .T Endoscopic excision of a foreign body in the pyloric channel. .P JOURNAL ARTICLE. .A D'Auria DA; Naidorf T; Hashmi MA; Levine SM. .I 275109 .U 91007150 .S Gastrointest Endosc 9101; 36(4):408-9 .M Adenocarcinoma/*RA; Aged; Case Report; Cholangiopancreatography, Endoscopic Retrograde/*; Cystic Duct/*RA; Female; Hepatic Duct, Common/*RA; Human; Pancreatic Neoplasms/*RA. .T The pseudo-double duct sign: an ERCP finding in pancreatic carcinoma. .P JOURNAL ARTICLE. .A Morris JB; Zollinger RM Jr; Stellato TA; Yang P. .I 275110 .U 91007151 .S Gastrointest Endosc 9101; 36(4):410-1 .M Case Report; Cholangiopancreatography, Endoscopic Retrograde/*; Cystadenocarcinoma/*RA; Female; Human; Middle Age; Pancreatic Ducts/*RA; Pancreatic Neoplasms/*RA. .T ERCP in the diagnosis of ductectatic mucinous cystadenocarcinoma of the pancreas. .P JOURNAL ARTICLE. .A Dabezies MA; Campana T; Friedman AC. .I 275111 .U 91007152 .S Gastrointest Endosc 9101; 36(4):412-3 .M Electrosurgery/AE/*MT; Endoscopy; Human; Radio Waves/*/AE. .T Endoscopic radio frequency electrosurgery [editorial] .P EDITORIAL. .A Tucker RD; Sievert CE; Vennes JA; Silvis SE. .I 275112 .U 91007153 .S Gastrointest Endosc 9101; 36(4):413-5 .M Endoscopy, Gastrointestinal/*TD; England; Human; Publishing. .T British endoscopy: recent highlights [editorial] .P EDITORIAL. .A Cotton PB; Baillie J. .I 275113 .U 91007154 .S Gastrointest Endosc 9101; 36(4):417-8 .M Endoscopy, Gastrointestinal/*; Gagging/*PH; Human; Hypnotics and Sedatives/*TU. .T Sedation for upper gastrointestinal endoscopy: time for reappraisal? [letter; comment] .P COMMENT; LETTER. .A Ladas SD; Giorgiotis G; Pipis P; Papaioannou C; Tassios P; Karra E; Raptis SA. .I 275114 .U 91007155 .S Gastrointest Endosc 9101; 36(4):418 .M Case Report; Cecal Neoplasms/*SU; Electrocoagulation/*AE; Gastrointestinal Hemorrhage/*ET; Human; Male; Middle Age; Polyps/*SU; Time Factors. .T Delayed hemorrhage following "hot biopsy" of a diminutive colonic polyp [letter; comment] .P COMMENT; LETTER. .A Nelson AM. .I 275115 .U 91007157 .S Gastrointest Endosc 9101; 36(4):419-20 .M Computers/*; Endoscopy/*IS; Equipment Failure. .T Endoscopic computer repair [letter] .P LETTER. .A Krevsky B; Matz L; Williams L. .I 275116 .U 91007158 .S Gastrointest Endosc 9101; 36(4):420-1 .M Balloon Dilatation/*MT; Case Report; Esophageal and Gastric Varices/*TH; Gastrointestinal Hemorrhage/*TH; Human; Intubation/*IS; Male; Middle Age. .T Minnesota tube placement using a guide wire [letter] .P LETTER. .A Snow ND; Almon M; Baillie J. .I 275117 .U 91007159 .S Gastrointest Endosc 9101; 36(4):421-2 .M Aged; Case Report; Colon/PA; Colonic Diseases/*DI; Colonoscopy; Giant Lymph Node Hyperplasia/*DI; Human; Male. .T Nodular lymphoid hyperplasia of the colon in adults: is it common? [letter] .P LETTER. .A Colarian J; Calzada R; Jaszewski R. .I 275118 .U 91007160 .S Gastrointest Endosc 9101; 36(4):422 .M Adult; Case Report; Colon/*PA; Colonoscopy/*; Hemoperitoneum/*DI; Human; Male. .T Shifting blue hue sign [letter] .P LETTER. .A Parithivel VS; Rosario PG; Subbarao M. .I 275119 .U 91007161 .S Gastrointest Endosc 9101; 36(4):422-3 .M Endoscopy/*IS; Equipment Design; Human; Protective Devices/*. .T A protective shield for the endoscopist [letter] .P LETTER. .A Gottesman JE; Medwell SJ. .I 275120 .U 91007162 .S Gastrointest Endosc 9101; 36(4):423-5 .M Case Report; Child; Corrosion; Esophagus/*; Female; Foreign Bodies/*; Human; Hydrogen-Ion Concentration; Saliva. .T The disappearing penny [letter] .P LETTER. .A Maccini DM; Bronson A. .I 275121 .U 91007163 .S Gastrointest Endosc 9101; 36(4):425 .M Cholestasis/*TH; Drainage/*MT; Female; Human; Intubation, Gastrointestinal; Male; Middle Age. .T Present day indications for nasobiliary drainage [letter] .P LETTER. .A Spinelli P; Meroni E; Stiriti A; Mancini A; Martino E. .I 275122 .U 91007164 .S Gastrointest Endosc 9101; 36(4):425-6 .M Aged; Case Report; Cholangiopancreatography, Endoscopic Retrograde; Fasciitis/*ET; Female; Human; Necrosis; Sphincterotomy, Transhepatic/*AE. .T Necrotizing fasciitis--a complication of "successful" endoscopic sphincterotomy [letter] .P LETTER. .A Welch NT; Ellis DJ; Bradby GV. .I 275123 .U 91007165 .S Gastrointest Endosc 9101; 36(4):426-7 .M Aged; Aged, 80 and over; Arteries/IN; Case Report; Female; Hemoperitoneum/*ET; Human; Sphincterotomy, Transhepatic/*AE; Stomach/*BS. .T Intraperitoneal hemorrhage from injury to the gastroepiploic artery: a complication of endoscopic retrograde sphincterotomy [letter] .P LETTER. .A Risher WH; Smith JW. .I 275124 .U 91007166 .S Gastrointest Endosc 9101; 36(4):427 .M Case Report; Cholangiopancreatography, Endoscopic Retrograde/*AE; Female; Hepatic Duct, Common/*IN; Human; Middle Age. .T Common hepatic duct perforation: a rare complication associated with ERCP [letter] .P LETTER. .A Coelho JC; Campos AC; Pisani JC; Salles PM; Moss AA Jr. .I 275125 .U 91007292 .S Geriatrics 9101; 45(10):17 .M Aged; Diet/*; Human; Nutrition/*ED; Nutritional Requirements/*. .T Geriatric nutrition: advice from an expert panel [editorial] .P EDITORIAL. .A Butler RN. .I 275126 .U 91007293 .S Geriatrics 9101; 45(10):18-9 .M Aged; Aged, 80 and over; Aging/*DE; Clinical Trials; Ethics, Medical; Human; Injections, Subcutaneous; Insulin-Like Growth Factor I/AE/PD/*TU; Male. .T Human growth hormone: the Fountain of Youth? .P JOURNAL ARTICLE. .A Walker C. .I 275127 .U 91007294 .S Geriatrics 9101; 45(10):26-31, 34 .M Aged; Drug Interactions; Human; Nutrition/*ED; Nutrition Disorders/ET/*PC/PP; Nutritional Requirements/*; Patient Education; Vitamins/TU; Weight Loss. .T Practical nutritional advice for the elderly, Part I: Evaluation, supplements, RDAs. A geriatrics panel discussion. .P JOURNAL ARTICLE. .W By the time someone reaches old age, he or she thinks they know everything they want, or need, to know about nutrition. Yet malnutrition and its many effects are a rising danger. In this first of two installments of a panel discussion, nutritional experts review practical concerns for the treating physician, including assessment, interpretation of weight loss, use of supplements, and the relevance of RDAs to the elderly. .I 275128 .U 91007295 .S Geriatrics 9101; 45(10):37-43 .M Aged; Dementia/*DI/ET; Depressive Disorder/*DI/DT/ET; Diagnosis, Differential; Family Practice; Grief/*; Human; Physician's Role. .T Dementia, depression, or grief? The differential diagnosis. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Depression, grief, and dementia are conditions frequently encountered among the community-living elderly. This review offers a primary care perspective of the distinguishing features for each and discusses the special issues of managing the elderly. Major depression in the elderly usually responds to antidepressant medication, whether the depression occurs alone (endogenous) or as a response to another condition (reactive). .A Brock C; Simpson WM. .I 275129 .U 91007296 .S Geriatrics 9101; 45(10):45-8 .M Adult; Aged; Case Report; Female; Geriatric Assessment/*; Human; Informed Consent/*LJ; Living Wills/*LJ; Physician's Role/*; United States. .T Assessing competency in the elderly. .P JOURNAL ARTICLE. .W The doctrine of informed consent requires that a patient understand the medical procedure being proposed, that consent be voluntary, and that the patient be competent to give consent. Because of declining cognitive functioning, elderly patients are at significant risk of becoming incompetent and, therefore, unable in the eyes of the law to give informed consent. Advance directives allow competent patients to tell their doctors and the world in general what their health care choices are should they not be able to make their choices clear in the future. The living will and durable power of attorney are two types of advance directives that are legally binding in most states. .A Janofsky JS. .I 275130 .U 91007297 .S Geriatrics 9101; 45(10):49-52, 55 .M Aged; Antibiotics/TU; Human; Incidence; Pneumonia/*DI/DT/EP; Risk Factors. .T Pneumonia syndromes: a clinical approach in the elderly. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Important in the pathogenesis of pneumonia in the elderly patient are chronic diseases, including diabetes mellitus, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, and cerebrovascular disease. Also vital are the changes that take place in the immune system and mucociliary clearance mechanisms of the lung. The clinician should be aware of these risk factors, especially since the mortality rate of lower respiratory infections approaches 40% in these elderly patients. Treatment guidelines are included. .A Cunha BA; Gingrich D; Rosenbaum GS. .I 275131 .U 91007298 .S Geriatrics 9101; 45(10):57-9, 63-6 .M Aged; Diagnosis, Differential; Human; Skin Diseases/*DI/DT/PA. .T Aging and the skin: recognizing and managing common disorders. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Senescent changes in structure and function of the skin and chronic solar radiation damage predispose the skin of the elderly to certain inflammatory and infectious diseases. In this context, the diagnosis and treatment of senile xerosis and pruritus are discussed, as are the common types of dermatitides, infections, and infestations. .A Shenefelt PD; Fenske NA. .I 275132 .U 91007299 .S Geriatrics 9101; 45(10):68-70, 75 .M Aged; Aging/PH; Alzheimer's Disease/*CO; Dementia, Senile/*CO/PP; Diagnosis, Differential; Human; Language Disorders/CL/*DI/ET; Semantics/*. .T Semantic deterioration in Alzheimer's: the patterns to expect. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Differentiating language changes between the normal aged and those in the early stages of dementia is never simple. Knowing the differences and what to expect can aid in making this diagnosis. .A Chobor KL; Brown JW. .I 275133 .U 91007300 .S Geriatrics 9101; 45(10):78-9 .M Certification/*; Clinical Competence/*ST; Geriatrics/*ST; Human. .T Is the special competency exam fair to primary care? [letter; comment] .P COMMENT; LETTER. .I 275134 .U 91007392 .S Gut 9101; 31(9):1003-5 .M Adult; Duodenum/*PH; Eating/*PH; Electromyography; Electrophysiology; Female; Gastric Emptying; Gastrointestinal Transit/*; Human; Male; Support, Non-U.S. Gov't. .T Human migrating myoelectric complex in relation to gastrointestinal transit of a meal. .P JOURNAL ARTICLE. .W Feeding interrupts the migrating myoelectric complex in most mammals. This study aimed to assess whether resumption of the migrating myoelectric complex in the human duodenum after eating was related to the gastrointestinal transit of the meal. Five healthy subjects participated in the study. After eating a radiolabelled test meal consisting of mixed liquid and solids, duodenal myoelectric activity and gastrointestinal transit of the meal were determined simultaneously. In spite of considerable variation in entire gastric emptying time between subjects (range 2.5-5.0 hours), significant correlation was found between the completion of gastric emptying and the resumption of duodenal phase III activity within subjects (p less than 0.01). A new technique for recording the duodenal myoelectric activity was used. .A Madsen JL; Dahl K. .I 275135 .U 91007393 .S Gut 9101; 31(9):1006-10 .M Animal; Blood Volume/*PH; Duodenum/*PH; Extracellular Space/*PH; Gastrointestinal Transit/*; Hemorrhage/PP; Isotonic Solutions; Male; Rats; Rats, Inbred Strains; Sodium Chloride/*; Stomach/*PH. .T Acute hypervolaemia increases gastroduodenal resistance to the flow of liquid in the rat. .P JOURNAL ARTICLE. .W The effect of volume expansion of extracellular fluid on gastroduodenal resistance to the flow of isotonic saline was assessed in three groups of rats using intravenous infusions of isotonic, isotonic-isoncotic, and isotonic-isoncotic-isohaemic solutions. The gastroduodenal segment of 29 male Wistar rats was barostatically perfused at a constant pressure gradient of 4 cm H2O and changes in flow (ml/minute) were taken as a reflection of changes in gastroduodenal resistance. Isotonic expansion led to a 33% drop in gastroduodenal flow compared with the normovolaemic period in the same animals (p less than 0.01). Extracellular fluid expansion with isotonic-isoncotic and isotonic-isoncotic-isohaemic solutions was associated with reductions in gastroduodenal flow of 29% (p less than 0.05) and 31% (p less than 0.01) respectively. The increase in gastroduodenal resistance is due to hypervolaemia per se and not to haemodilution, decreases in plasma oncotic pressure, or electrolyte imbalance. The effect of hypervolaemia on gastroduodenal resistance, which was reversed by small haemorrhages (0.5-1.0 ml per 100 g body weight), may be due to changes in tonus or phasic motor activity, or both, and may be part of the homeostatic processes that help the organism minimise liquid volume excess. .A Xavier-Neto J; dos Santos AA; Rola FH. .I 275136 .U 91007394 .S Gut 9101; 31(9):1011-5 .M Animal; Bacterial Adhesion; Cell Movement; Epithelium/MI/UL; Female; Ileum/MI; Mice; Microscopy, Electron; Microvilli/MI; Peyer's Patches/*MI/UL; Support, Non-U.S. Gov't; Yersinia enterocolitica/IM/*PY. .T Involvement of M cells in the bacterial invasion of Peyer's patches: a common mechanism shared by Yersinia enterocolitica and other enteroinvasive bacteria. .P JOURNAL ARTICLE. .W Recent evidence indicates that ileal Peyer's patches represent the main infection route for Yersinia enterocolitica. In this study transmission and scanning electron microscopy have shown that only a small fraction of bacteria present in the lumen adhere to the follicle-associated murine epithelium with no discernible preference for either M or absorptive cells. Yersiniae attached to M cells are phagocytosed and transported from the lumen into the lamina propria. No invasion of columnar absorptive cells was observed. These data, in combination with recently published reports, indicate that the involvement of M cells is a common step in bacterial invasion of Peyer's patches. .A Grutzkau A; Hanski C; Hahn H; Riecken EO. .I 275137 .U 91007395 .S Gut 9101; 31(9):1016-20 .M Adolescence; Adult; Aged; Antibody Specificity; Autoantibodies/*AN/IM; Autoantigens/*IM; Colitis, Ulcerative/*IM; Colon/*IM; Crohn Disease/IM; Enzyme-Linked Immunosorbent Assay; Female; Human; Male; Middle Age; Support, Non-U.S. Gov't. .T Circulating antibodies against human colonic extract enriched with a 40 kDa protein in patients with ulcerative colitis. .P JOURNAL ARTICLE. .W We have previously described a 40 kDa colonic protein(s) which is specifically recognised by tissue-bound immunoglobulin G obtained from the colon of patients with ulcerative colitis. We now report the presence of circulating antibodies against this antigen using an enzyme-linked immunosorbent assay with a highly enriched preparation of the 40 kDa protein from normal colon extracts. Serum was collected from 79 patients with ulcerative colitis, 36 with Crohn's disease, 16 with specific diarrhoeal syndromes, and from 19 normal subjects. Twenty nine of 79 patients with ulcerative colitis, 21 of 36 with Crohn's disease, and all patients with diarrhoea were symptomatic during the collection of sera. The difference in optical density values between patients with symptomatic ulcerative colitis and each of the other groups, including patients with ulcerative colitis in remission, was highly significant (p less than 0.01). Seventy nine per cent of patients with symptomatic ulcerative colitis had optical density values above the means for all other groups. Fifty five per cent of sera from patients with symptomatic ulcerative colitis had optical densities beyond two SDs of the values for all other groups and only two of 71 sera from non-ulcerative colitis patients (one Crohn's disease and one normal subject) had values in this range. These results show the presence of anti-colon antibodies against the 40 kDa protein(s) in the sera of many patients with symptomatic ulcerative colitis. .A Takahasi F; Shah HS; Wise LS; Das KM. .I 275138 .U 91007396 .S Gut 9101; 31(9):1021-4 .M Adult; Aged; Blood Flow Velocity; Colitis, Ulcerative/ET/*PP; Female; Human; Male; Middle Age; Nicotine/BL; Rectum/*BS; Regional Blood Flow; Smoking/*PP. .T Effect of ulcerative colitis and smoking on rectal blood flow. .P JOURNAL ARTICLE. .W Rectal blood flow was measured by laser doppler flowmetry over 60 minutes in eight patients with colitis in remission and eight healthy male non-smokers. Ten smokers were also examined on two occasions, one of which included smoking a cigarette. Plasma nicotine concentrations were measured in smokers. All subjects showed a pronounced fall in rectal blood flow in the first 30 minutes and patients with colitis had significantly higher values compared with smokers (p less than 0.002; p less than 0.04) and non-smokers (p less than 0.007; p less than 0.002) during the first and second 30 minutes respectively. Values in smokers and non-smokers were similar, but smoking a cigarette was associated with a significant fall in blood flow (p less than 0.04) and this change was inversely related to the rise in plasma nicotine concentration (r = -0.63; p less than 0.05). The findings may be relevant to the association between colitis and the smoking history. .A Srivastava ED; Russell MA; Feyerabend C; Rhodes J. .I 275139 .U 91007397 .S Gut 9101; 31(9):1025-9 .M Circadian Rhythm/*; Esophagitis, Peptic/*DT; Female; Gastroesophageal Reflux/ME/*PC/PP; Human; Hydrogen-Ion Concentration; Male; Middle Age; Prospective Studies; Ranitidine/*TU; Recurrence. .T Daytime reduction of gastro-oesophageal reflux after healing of oesophagitis and its value as an indicator of favourable response to maintenance treatment. .P JOURNAL ARTICLE. .W In order to investigate the response of gastro-oesophageal reflux after medically induced healing of oesophagitis and its relation to the occurrence of relapse during prophylactic treatment, 20 patients with erosive/ulcerative oesophagitis underwent 24 hour oesophageal pH monitoring before and after healing achieved with 12 to 24 week treatment with ranitidine 150 or 300 mg twice daily. Compared with pretreatment values, after macroscopic healing, a significant reduction in daytime median percentage of reflux time (10.0 v 6.5; p less than 0.05) and median number of reflux episodes lasting more than 5 minutes (5-5 v 1.0; p less than 0.05) were observed, whereas during night time reflux frequency and severity did not change. During maintenance treatment with ranitidine 150 or 300 mg nocte, five of the six patients, who had shown no improvement in gastro-oesophageal reflux after acute healing, relapsed. These results suggest that, in contrast with previous work, a decrease in gastro-oesophageal reflux in patients with reflux oesophagitis can be achieved after macroscopic healing, and that the occurrence of such a reduction after acute healing is predictive of a good response to longterm treatment. .A Pace F; Sangaletti O; Bianchi Porro G. .I 275140 .U 91007398 .S Gut 9101; 31(9):1030-2 .M Aminosalicylic Acids/*PD; Colitis, Ulcerative/IM; Crohn Disease/IM; Cytotoxicity Tests, Immunologic; Cytotoxicity, Immunologic/*DE; Double-Blind Method; Human; Immunosuppressive Agents/*PD; Killer Cells, Natural/*DE/IM; Random Allocation; Salicylazosulfapyridine/*PD; Support, Non-U.S. Gov't. .T Inhibition of cell mediated cytotoxicity by sulphasalazine: effect of in vivo treatment with 5-aminosalicylic acid and sulphasalazine on in vitro natural killer cell activity. .P JOURNAL ARTICLE. .W Decreased cell mediated cytotoxicity occurs frequently in inflammatory bowel disease, particularly in patients with active disease. It is not clear, however, whether this decrease is caused by the disease or is a consequence of the medical treatment. In this study we evaluated the effect of in vivo treatment with 5-aminosalicylic acid and sulphasalazine on the in vitro natural killer cell activity in five patients with inflammatory bowel disease in remission and in four healthy control subjects in a double blind randomised crossover trial preceded and separated by four weeks of treatment with placebo. The natural killer cell activity was significantly impaired in 67% (six of nine subjects) after four weeks' sulphasalazine treatment and tended to be related to subjects with a slow acetylator phenotype. In contrast, 5-aminosalicylic acid treatment caused only a marginal reaction in the natural killer cell activity in 22% (two of nine subjects). The inhibitory effects were found to be reversible since the decreased natural killer cell activity was completely restored after placebo treatment in all subjects. In conclusion, in vivo treatment with sulphasalazine inhibits the in vitro natural killer cell activity and this seems to be mediated by the sulphapyridine moiety. This phenomenon may contribute to the low natural killer cell activity found in patients with active inflammatory bowel disease. .A Aparicio-Pages MN; Verspaget HW; Hafkenscheid JC; Crama-Bohbouth GE; Pena AS; Weterman IT; Lamers HW. .I 275141 .U 91007399 .S Gut 9101; 31(9):1033-6 .M alpha 1-Antitrypsin/AN; Adult; C-Reactive Protein/AN; Crohn Disease/BL/*IM; Female; Human; Male; Platelet Count; Receptors, Interleukin-2/*BL; Severity of Illness Index; Support, Non-U.S. Gov't. .T Soluble interleukin-2 receptor in Crohn's disease: relation of serum concentrations to disease activity. .P JOURNAL ARTICLE. .W Serum concentrations of soluble interleukin-2 receptor (sIL-2R) were measured as a marker of immune activation in a group of 30 patients with Crohn's disease. sIL-2R concentrations were determined by enzyme linked immunosorbent assay during periods of active and inactive disease and correlated with standard parameters of disease activity. Serum concentrations of sIL-2R were significantly raised in patients with active Crohn's disease compared with patients with inactive disease (p less than 0.001) and control subjects. There was a significant correlation between serum sIL-2R concentrations and disease activity as assessed by the Harvey-Bradshaw index (r = 0.42, p less than 0.01), platelet numbers (r = 0.49, p less than 0.01), and orosomucoid (r = 0.47, p less than 0.01), alpha 1 antitrypsin (r = 0.44, p less than 0.01), and C reactive protein concentrations (r = 0.48, p less than 0.001) but not with the erythrocyte sedimentation rate. Measurement of serum sIL-2R concentration is a simple and useful laboratory means of assessing disease activity. Raised concentrations in patients with active Crohn's disease is further evidence for in vivo immune activation occurring in this disease. .A Crabtree JE; Juby LD; Heatley RV; Lobo AJ; Bullimore DW; Axon AT. .I 275142 .U 91007400 .S Gut 9101; 31(9):1037-40 .M Colitis, Ulcerative/*EP/RH; Crohn Disease/*EP/RH; Environment, Controlled; Female; Germany, West; Human; Male; Occupational Diseases/CL/*EP/RH; Risk Factors; Sex Factors; Support, Non-U.S. Gov't; Work Schedule Tolerance. .T Occupational distribution of inflammatory bowel disease among German employees. .P JOURNAL ARTICLE. .W Previous reports have shown that both Crohn's disease and ulcerative colitis affect people in white collar occupations associated with higher income and higher social class more frequently than other groups in the population. This study sought to carry these analyses one step further and investigate the distribution of inflammatory bowel disease by individual occupations. The German social security statistics for 'rehabilitation' were used to assess the occupational distribution of Crohn's disease and ulcerative colitis. From 1982 to 1988, a total of 12,014 people were granted rehabilitation as a result of inflammatory bowel disease. Low male prevalence of inflammatory bowel disease was found among bricklayers, road construction workers, unskilled workers in brick and stone, unskilled labourers, and security personnel. Low rates were found among women employed in cleaning and maintenance, and in those without occupation. In contrast, a high male prevalence was found among instrument makers, electricians, bakers, and technical assistants. Among female employees, inflammatory bowel disease was significantly associated with sales representatives, office workers, health occupations, and hairdressers. These associations were found in the complete data for 1982-8 as well as in the separate data for the two half periods 1982-5 and 1986-8. Highly significant correlations between the occupational distribution of Crohn's disease and ulcerative colitis were found among both male and female employees. It seems that occupations involving work in the open air and physical exercise are protective, while being exposed to air conditioned artificial working conditions or extended and irregular shift working confer a risk of contracting inflammatory bowel disease. .A Sonnenberg A. .I 275143 .U 91007401 .S Gut 9101; 31(9):1041-5 .M Adenocarcinoma/*CH/PA; Adenoma/*CH/PA; Adult; Aged; Colon/CH; Colonic Neoplasms/*CH/PA; Colonic Polyps/CH; Colorectal Neoplasms/*CH/PA; Diglycerides/*AN; Female; Human; Intestinal Mucosa/CH; Male; Middle Age; Reference Values; Second Messenger Systems; Support, Non-U.S. Gov't. .T Low diacylglycerol values in colonic adenomas and colorectal cancer. .P JOURNAL ARTICLE. .W The biochemical events that make colonic epithelial cells proceed along the adenoma-carcinoma sequence are not well understood. The phosphoinositol signal transduction pathway is involved in the regulation of cell growth and differentiation. To determine its role in colonic neoplasias we performed mass measurements of its second messenger sn-1,2-diacylglycerol in biopsy specimens from normal mucosa and neoplasias of the colon. Normal colonic mucosa was also investigated in patients without colonic abnormalities (n = 10). Compared with pooled diacylglycerol values from five colonic sites (100%), values in patients with a normal colon were highest in the ascending colon (120 (5)%, p less than 0.05) and lowest in the rectum (81 (5)%, p less than 0.01). Absolute diacylglycerol values in patients with normal colons (2.62 (0.16) nmol/mg protein) were not significantly different from those found in the normal mucosa of patients with colorectal neoplasias (2.45 (0.17) nmol/mg protein). Both colonic adenomas (n = 15) and colorectal carcinomas (n = 14) showed significantly decreased diacylglycerol values compared with the adjacent normal mucosa of each patient (72 (4)%, p less than 0.001, and 71 (4)%, p less than 0.001 respectively). The appreciable decrease in mass diacylglycerol values clearly distinguishes adenomas and carcinomas of the colon from the surrounding normal mucosa. This finding suggests that profound metabolic changes of the phosphoinositol signal transduction pathway occur early in the adenoma-carcinoma sequence and may be important in colonic carcinogenesis. .A Sauter G; Nerlich A; Spengler U; Kopp R; Pfeiffer A. .I 275144 .U 91007402 .S Gut 9101; 31(9):1046-50 .M Acetylcholine/*ME/PH; Child, Preschool; Colon/*IR/ME/PP; Electric Stimulation; Ganglia/ME/*PP; Hirschsprung Disease/*PP; Human; Infant; Muscle Contraction; Neural Transmission/*; Receptors, Adrenergic, Alpha/ME/PH. .T Characteristics of cholinergic neuroeffector transmission of ganglionic and aganglionic colon in Hirschsprung's disease. .P JOURNAL ARTICLE. .W Differences in the release and content of acetylcholine and the alpha 2 adrenoceptor mediated interaction between noradrenergic and cholinergic neurons were investigated by neurochemical and pharmacological methods in aganglionic and ganglionic segments of isolated human colon taken from children suffering from Hirschsprung's disease. Both at rest and during transmural stimulation the release of acetylcholine was significantly higher in the spastic (aganglionic) segment than in the proximal dilated bowel. Significant differences were found in the tissue concentration of acetylcholine between ganglionic and aganglionic specimens. The pattern of response to transmural stimulation was also different in the spastic and dilated bowel. Transmural stimulation induced relaxation and contraction in ganglionic specimens but only contractions in aganglionic specimens. The sensitivity of the smooth muscle in the aganglionic portion to exogenous acetylcholine and to field stimulation was found to be higher than in the ganglionic portion. While noradrenaline added to the organ bath reduced the stimulation-evoked release of acetylcholine from spastic segments, via an alpha 2 adrenoceptor mediated process, yohimbine did not enhance the release. It is suggested that in Hirschsprung's disease the increased acetylcholine release, the enhanced sensitivity of smooth muscle cells to acetylcholine, and the lack of alpha 2 adrenoceptor mediated noradrenergic modulation of acetylcholine release from cholinergic interneurons might be responsible for the spasm of aganglionic segments. .A Vizi ES; Zseli J; Kontor E; Feher E; Verebelyi T. .I 275145 .U 91007403 .S Gut 9101; 31(9):1051-5 .M Adult; Aged; Anus/*IR/PP; Electric Stimulation Therapy/*; Electromyography; Electrophysiology; Fecal Incontinence/ET/PP/*TH; Female; Human; Manometry; Middle Age; Peripheral Nerve Diseases/CO; Reaction Time; Reflex/*; Support, Non-U.S. Gov't. .T Use of the pudendo-anal reflex in the treatment of neurogenic faecal incontinence. .P JOURNAL ARTICLE. .W An electrical stimulator has been devised to treat neurogenic faecal incontinence caused by pudendal nerve neuropathy and works on the basis of repeated stimulation of the pudendo-anal reflex arc. Although conduction in the pudendo-anal reflex arc may be prolonged, and is so in neurogenic faecal incontinence, it must be shown to be present before the method can be used. This stimulation results in an immediate rise in the pressure in the anal canal and a significant increase in the electromyographic activity of the external anal sphincter. Maintenance of the stimulus over a two month period raised the mean resting pressure significantly in the anal canal and increased the reflex and voluntary responses of the external anal sphincter to coughing and squeezing actions respectively. The length of the sphincter was not affected. There was widening of the mean motor unit potential duration, though this was not significant. The resting electromyogram was enhanced after the course of treatment, indicating greater spontaneous activity in the external sphincter. The changes led to seven of the eight patients studied becoming continent at the end of the treatment. .A Binnie NR; Kawimbe BM; Papachrysostomou M; Smith AN. .I 275146 .U 91007404 .S Gut 9101; 31(9):1056-61 .M Adult; Aged; Anus/PP; Comparative Study; Fecal Incontinence/*PP; Female; Human; Male; Middle Age; Muscle Contraction; Pressure; Rectum/PH/*PP; Reference Values; Sensation/*. .T Relation between rectal sensation and anal function in normal subjects and patients with faecal incontinence. .P JOURNAL ARTICLE. .W The relation between sensory perception of rapid balloon distension of the rectum and the motor responses of the rectum and external and internal anal sphincters in 27 normal subjects and 16 patients with faecal incontinence who had impaired rectal sensation but normal sphincter pressures was studied. In both patients and normal subjects, the onset and duration of rectal sensation correlated closely with the external anal sphincter electrical activity (r = 0.8, p less than 0.0001) and with rectal contraction (r = 0.51, p less than 0.001), but not with internal sphincter relaxation. All normal subjects perceived a rectal sensation within one second of rapid inflation of a rectal balloon with volumes of 20 ml or less air. Six patients did not perceive any rectal sensation until 60 ml had been introduced, while in the remaining nine patients the sensation was delayed by at least two seconds. Internal sphincter relaxation occurred before the sensation was perceived in three of 27 normal subjects and 11 of 16 patients (p less than 0.001), and could be associated with anal leakage, which stopped as soon as sensation was perceived. The lowest rectal volumes required to induce anal relaxation, to cause sustained relaxation, or to elicit sensations of a desire to defecate or pain were similar in patients and normal subjects. In conclusion, these results show the close association between rectal sensation and external anal sphincter contraction, and show that faecal incontinence may occur as a result of delayed or absent external anal sphincter contraction when the internal anal sphincter is relaxed. .A Sun WM; Read NW; Miner PB. .I 275147 .U 91007405 .S Gut 9101; 31(9):1062-8 .M Adolescence; Adult; Aged; Colonic Diseases, Functional/*PP; Female; Human; Male; Middle Age; Pressure; Rectum/PH/*PP; Reference Values; Sensation; Support, Non-U.S. Gov't. .T Inter- and intraindividual variation in pressure-volume relations of the rectum in normal subjects and patients with the irritable bowel syndrome. .P JOURNAL ARTICLE. .W The relation between intrarectal volume and pressure during increasing rectal distension by a latex balloon were studied on repeated occasions in 10 healthy adult volunteers to define variations within and between individuals. A wide intersubject variation in the maximum tolerable volume (58-908 ml) and pressure (12.2-108.8 cm H2O) at this end point was seen, and these two values were correlated (r = 0.78). Intrasubject variation in maximum tolerable volume also occurred which was related to study order and progressively reduced with repeated study. In 26 unselected patients with pain predominant irritable bowel syndrome similar intersubject variation was noted and virtually all patients data fell within the calculated 95% confidence limits of the normal individuals. Differentiation between patients and normal subjects was not possible from knowledge of rectal responses. These noticeable inter- and intrasubject variations in rectal responses to distension need to be considered whenever similar techniques are proposed for use in the study of rectal disease or of rectal response to treatment. .A Kendall GP; Thompson DG; Day SJ; Lennard-Jones JE. .I 275148 .U 91007406 .S Gut 9101; 31(9):1069-72 .M Adult; Aged; Bilirubin/BL; Female; Human; Liver Cirrhosis, Biliary/BL/MO/*SU; Liver Transplantation/*; Male; Middle Age; Postoperative Complications/MO; Prognosis; Referral and Consultation/*; Retrospective Studies. .T Referral of patients with primary biliary cirrhosis for liver transplantation. .P JOURNAL ARTICLE. .W All patients with primary biliary cirrhosis referred to this unit for consideration for transplantation between April 1981 and January 1989 were analysed retrospectively to assess whether disease stage at referral affects the outcome after grafting and whether greater awareness of the benefits of the procedure means that patients are now being referred at an earlier stage. Seventy of the 107 patients have been grafted, with an overall one year actuarial survival of 62%. A better prognosis at the time of referral, as assessed by both serum bilirubin concentration and a mathematically derived prognostic index, was associated with a greater probability of survival after grafting. Patients in the tertile with the best prognosis (median serum bilirubin concentration at referral 84 mumol/l and estimated survival in the absence of transplantation of more than nine months) had a 78% one year actuarial survival after transplantation, whereas those in the tertile with the worst prognosis (median serum bilirubin concentration 467 mumol/l and estimated survival of less than four months) had a one year actuarial survival of only 50%. No trend towards earlier referral of patients, however, was shown using either of these two markers. This retrospective analysis suggests that many patients are being referred too late for an optimal outcome. We recommend that patients with primary biliary cirrhosis who are potential candidates for liver grafting should be referred to a transplant centre before the serum bilirubin concentration approaches 150 mumol/l. .A Neuberger JM; Gunson BK; Buckels JA; Elias E; McMaster P. .I 275149 .U 91007407 .S Gut 9101; 31(9):1073-5 .M Adult; Age Factors; Aged; Cholangiopancreatography, Endoscopic Retrograde; Cholelithiasis/CO/*PA; Chronic Disease; Female; Human; Male; Middle Age; Pancreatic Ducts/*PA; Pancreatitis/ET. .T Pancreatic duct abnormalities in gall stone disease: an endoscopic retrograde cholangiopancreatographic study. .P JOURNAL ARTICLE. .W This study was carried out to assess pancreatic duct abnormalities in gall stone disease. Endoscopic retrograde cholangiopancreatograms of 50 patients with gall stone disease were analysed and the results compared with those obtained in 33 patients investigated for cholestatic jaundice who were found to have a normal biliary tree (control group). Abnormal pancreatograms were obtained in 24 (48%) patients with gall stone disease and in only two (6%) in the control group; the differences were statistically significant (chi 2 = 14.3; p less than 0.001). The patients in the control group showed mild abnormalities as did those in the gall stone group. The frequency of various abnormalities were: mild 16 (32%), moderate five (10%), and severe three (6%). Pancreatic duct abnormalities were more severe and occurred more frequently in patients with gall stones who had stones in the biliary tree than in patients with a normal biliary tree (postcholecystectomy patients, 55% v 25%) but the difference between the two groups just failed to be significant (chi 2 = 3.34). In conclusion, nearly half of all patients with gall stone disease have pancreatic duct abnormalities and in 16% these were severe enough to be labelled as chronic pancreatitis. .A Misra SP; Gulati P; Choudhary V; Anand BS. .I 275150 .U 91007408 .S Gut 9101; 31(9):1076-9 .M Adolescence; Adult; Aged; Aged, 80 and over; Amylases/AN; Crohn Disease/EN/*PP; Duodenum/EN; Female; Human; Lipase/AN; Male; Middle Age; Pancreas/EN/*PP; Pancreatic Function Tests. .T Pancreatic function in Crohn's disease. .P JOURNAL ARTICLE. .W We investigated exocrine pancreatic function in a population of patients with Crohn's disease in order to correlate the pancreatic function with clinical and laboratory variables. A total of 143 patients affected by Crohn's disease and 115 control subjects were studied. All had a Lundh meal test. As a group patients with Crohn's disease had significantly decreased activity of both amylase (p less than 0.02) and lipase (p less than 0.001) in duodenal aspirates. In patients with Crohn's disease enzyme activities were not correlated to duration of disease or to extent or localisation of previous bowel resection. The lowest enzyme values were found in patients with the most extensive bowel involvement, and they were significantly lower (p less than 0.05) than in patients with disease confined to the terminal ileum. The differences between enzyme values in other subgroups of patients were not significant. For the patient group as a whole no correlation was found between disease activity and enzyme values, but for the most uniform group of patients, those with terminal ileitis, pancreatic function was significantly lower (p less than 0.05) in patients with moderate and severe disease compared with patients with mild disease. Thus at least two factors seem to be responsible for impaired pancreatic function in Crohn's disease: firstly disease activity and secondly localisation or extent of disease. .A Hegnhoj J; Hansen CP; Rannem T; Sobirk H; Andersen LB; Andersen JR. .I 275151 .U 91007409 .S Gut 9101; 31(9):1080-1 .M Case Report; Celiac Disease/*PA; Duodenum/*PA; Endoscopy; Female; Human; Intestinal Mucosa/*PA; Male; Middle Age. .T Loss of duodenal folds allows diagnosis of unsuspected coeliac disease. .P JOURNAL ARTICLE. .W We report three patients with coeliac disease who presented without the classic features of malabsorption and who underwent biopsy and were diagnosed only because of the endoscopic finding of the disappearance of Kerckring's folds in the descending duodenum. This sign constitutes a new and valid aid for the identification of patients with otherwise unsuspected coeliac disease. .A Corazza GR; Brocchi E; Caletti G; Gasbarrini G. .I 275152 .U 91007410 .S Gut 9101; 31(9):1082-3 .M Adult; Case Report; Cholestasis/DI/*ET; Cysts/*CO/DI; Diagnosis, Differential; Human; Liver Diseases/*CO/DI; Male. .T Adult hepatic fibropolycystic disease presenting as obstructive jaundice. .P JOURNAL ARTICLE. .W Obstructive jaundice caused by compression of the common hepatic duct by a simple hepatic cyst in a 31 year old Europid man is reported. The jaundice and duct compression resolved after percutaneous aspiration of the cyst under ultrasound direction and the patient has been well for 12 months. .A Williams AJ; Wild SR; Palmer KR. .I 275153 .U 91007411 .S Gut 9101; 31(9):1086 .M Bismuth/*AE/BL; Half-Life; Human; Organometallic Compounds/*AE/BL. .T Anomalous short plasma elimination half life in a patient intoxicated with bismuth subcitrate [letter; comment] .P COMMENT; LETTER. .A McLean AJ; Islam S; Lambert JR. .I 275154 .U 91007412 .S Gut 9101; 31(9):1086-7 .M Human; Inflammatory Bowel Diseases/*IM; Macrophages/*ME; Oxygen Consumption. .T Macrophage activity in inflammatory bowel disease [letter; comment] .P COMMENT; LETTER. .A Mahida YR; Jewell DP. .I 275155 .U 91007413 .S Gut 9101; 31(9):1087-8 .M Gastric Acid/*SE; Gastrins/*BL; Histamine H2 Receptor Blockaders/*PD; Human; Piperidines/*PD; Triazoles/*PD. .T Intragastric acidity and serum gastrin after sufotidine [letter; comment] .P COMMENT; LETTER. .A Mela GS; Caputo E; Villa G; Savarino V; Zentilin P. .I 275156 .U 91007414 .S Gut 9101; 31(9):1088 .M Circadian Rhythm/*; Duodenal Ulcer/*DT; Gastric Acid/*SE; Human. .T Inhibition of nocturnal acidity [letter] .P LETTER. .A Primrose JN; Patel N; Rogers MR. .I 275157 .U 91007415 .S Gut 9101; 31(9):961-3 .M Autoimmune Diseases/CO/*IM; Human; Inflammatory Bowel Diseases/ET/*IM. .T Are the inflammatory bowel diseases autoimmune disorders? .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .A Snook J. .I 275158 .U 91007416 .S Gut 9101; 31(9):964-7 .M Adult; Aged; Barrett Esophagus/*ET/ME/PP; Esophagitis, Peptic/*CO/ME/PP; Esophagus/PP; Female; Human; Hydrogen-Ion Concentration; Male; Manometry; Middle Age. .T Evaluation of the magnitude of gastro-oesophageal reflux in Barrett's oesophagus. .P JOURNAL ARTICLE. .W A manometric study to determine the role of gastro-oesophageal reflux in Barrett's oesophagus was performed on 20 patients with Barrett's oesophagus and 53 patients with reflux oesophagitis without Barrett's oesophagus (25 with mild oesophagitis and 28 with severe oesophagitis). For the same reason, the 20 patients with Barrett's oesophagus also underwent 24 hour continuous oesophageal pH monitoring, and the results obtained were compared with those of 20 oesophagitis patients without Barrett's oesophagus (10 with mild oesophagitis and 10 with severe oesophagitis). The manometric results show that the motor changes found in the Barrett's group are specific but similar to the motor dysfunction associated with reflux oesophagitis. Motor anomalies are probably related more to the inflammatory process in the oesophageal wall than to the metaplastic changes themselves. The pH monitoring results show that while reflux in the Barrett's oesophagus patients was greater overall than in the oesophagitis group without Barrett's oesophagus, the changes are similar when the results are compared with the severe oesophagitis group. In conclusion there are other factors besides gastro-oesophageal reflux involved in the pathogenesis of Barrett's oesophagus. .A Parrilla P; Ortiz A; Martinez de Haro LF; Aguayo JL; Ramirez P. .I 275159 .U 91007417 .S Gut 9101; 31(9):968-72 .M Cimetidine/*TU; Comparative Study; Double-Blind Method; Esophagitis, Peptic/*DT/PA; Esophagoscopy; Esophagus/PA; Female; Human; Male; Middle Age; Omeprazole/*TU. .T Comparison of omeprazole and cimetidine in reflux oesophagitis: symptomatic, endoscopic, and histological evaluations. .P CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL. .W Symptomatic patients with endoscopically verified reflux oesophagitis were randomised to a double blind trial in which they received either omeprazole (20 mg once daily) or cimetidine (400 mg four times daily) for four, and if necessary, eight weeks. In an 'intention to treat' analysis, oesophagitis was found to have healed after four weeks in 77 of 137 (56%) in the omeprazole group and in 34 of 133 (26%) in the cimetidine group (p less than 0.001). By eight weeks these values were 71% and 35% respectively; p less than 0.001. Histological assessments were available for 73% of the patients. At entry, 63% (66 of 104) in the omeprazole group and 60% (56 of 94) in the cimetidine group (ns) had abnormal histology. After the study, the proportions of patients who initially had had abnormal histology but who then progressed to normal were 67% (44 of 66: omeprazole) and 48% (27 of 56: cimetidine) respectively (p less than 0.001). All patients had reflux symptoms at entry. After four weeks, 46% in the omeprazole group and 22% (p less than 0.001) in the cimetidine group were asymptomatic. Diary cards completed for the first two weeks showed that patients treated with omeprazole experienced fewer reflux symptoms by day and night and used fewer antacids. Omeprazole, 20 mg once a day for four to eight weeks, healed a greater proportion of patients with reflux oesophagitis than cimetidine, 1.6 g per day, assessed endoscopically and histologically, and relieved more patients' symptoms. .A Bate CM; Keeling PW; O'Morain C; Wilkinson SP; Foster DN; Mountford RA; Temperley JM; Harvey RF; Thompson DG; Davis M; et al. .I 275160 .U 91007418 .S Gut 9101; 31(9):973-6 .M Cefotaxime/*AA/TU; Cimetidine/TU; Drug Therapy, Combination; Female; Helicobacter pylori/*DE; Helicobacter Infections/*DT; Human; Male; Middle Age; Recurrence; Stomach Ulcer/ET/*PC. .T Reduction of gastric ulcer recurrence after suppression of Helicobacter pylori by cefixime. .P CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL. .W The effect on the recurrence of gastric ulcers after suppression of Helicobacter pylori by combined treatment with cimetidine and the antimicrobial drug cefixime was investigated. Twenty one of 43 patients with endoscopically proved gastric ulcer and H pylori infection were randomly assigned to receive cimetidine 800 mg daily for 12 weeks; the remaining 22 patients received cimetidine 800 mg daily for 12 weeks plus cefixime 100 mg daily for the last two weeks. After treatment, 88% of 17 patients on cimetidine only remained H pylori positive, whereas combined administration of cimetidine and cefixime had suppressed H pylori in 78% of 18 patients (p less than 0.05). Seventeen patients in the former group whose ulcers healed but who remained H pylori positive and 18 patients in the latter group whose ulcers healed and who were no longer infected with H pylori continued to be followed after treatment. These patients underwent endoscopy to detect ulcer recurrence if symptomatic, or at 12 and 24 weeks if asymptomatic. At 12 weeks, recurrence was observed in seven of 15 (47%) patients in whom H pylori persisted, but in only one of 14 (7%) patients in whom H pylori had been suppressed (p less than 0.05). At 24 weeks, however, recurrence rates were similar between the two groups. These findings indicate that H pylori infection may be closely related to early ulcer recurrence. .A Tatsuta M; Ishikawa H; Iishi H; Okuda S; Yokota Y. .I 275161 .U 91007419 .S Gut 9101; 31(9):977-83 .M Aged; Aged, 80 and over; Female; Gastrectomy; Gastric Mucosa/*PA; Human; Male; Middle Age; Polyps/PA; Precancerous Conditions/MO/*PA/SU; Stomach Neoplasms/MO/*PA/SU; Stomach Ulcer/PA. .T High grade dysplasia of the gastric mucosa: a marker for gastric carcinoma. .P JOURNAL ARTICLE. .W The natural history of gastric epithelial dysplasia and its relation to gastric cancer are ill defined. A consecutive series of 40 patients with an initial diagnosis of gastric epithelial dysplasia based on examination of endoscopic biopsies has been reviewed to determine the clinical outcome and to evaluate a two tier histological grading system as a predictor of the risk of cancer. On review, only 20 of the 40 patients were considered to have true dysplasia: seven patients had low grade dysplasia and 13 had high grade dysplasia. Of the 13 patients with high grade dysplasia, 11 (85%) were found to have gastric cancer within 15 months. Of the 10 patients with high grade dysplasia who underwent gastrectomy, six were found to have early gastric cancer, three had cancer invading into the muscularis propria, and none had lymph node metastases. High grade dysplasia is thus a marker of gastric cancer. Moreover, the cancers associated with high grade dysplasia are usually pathologically favourable and curable. The finding, by an experienced pathologist, of high grade dysplasia in two separate sets of endoscopic biopsies is therefore an indication for radical surgical treatment, provided that the patient's age and general condition permit such an approach. .A Lansdown M; Quirke P; Dixon MF; Axon AT; Johnston D. .I 275162 .U 91007420 .S Gut 9101; 31(9):984-8 .M Adult; Aged; Aged, 80 and over; Anastomosis, Surgical/*; Animal; Dogs; Electromyography/*; Fasting; Female; Gastrectomy/*; Human; Male; Middle Age; Muscle Contraction; Postoperative Period; Stomach/*PP/SU; Support, Non-U.S. Gov't. .T Myoelectrical activity of the Billroth II gastric remnant. .P JOURNAL ARTICLE. .W This study was undertaken to investigate the extent to which gastric electrical control activity and phasic contractile activity are preserved after Billroth II resection and to assess the relation between these activities and postprandial symptoms in patients who have undergone Billroth II resection. Thirty three patients were studied after Billroth II resection without vagotomy. Gastric electrical activity was recorded from surface electrodes and intraluminal pressure was recorded simultaneously. The electrogastrographic signals were analysed by Running Spectrum Analysis. In addition, three dogs with a Billroth II stomach and implanted serosal electrodes were studied. Phasic gastric pressure waves were observed in most patients. Electrogastrographic signals recorded from 82% of the Billroth II patients contained a mean (SD) peak at 3.1 (0.2) cycles per minute (cpm). Fasting and postprandial frequencies correlated significantly (p less than 0.02) with the score for nausea and vomiting. In 61% of the patients, the electrogastrographic signal contained a stable component with a frequency of 10.5 (0.6) cpm that was not caused by respiration. We suggest that this activity is of intestinal origin. In all three dogs studied, retrograde conduction of jejunal electrical control activity (16 cpm) into the distal part of the gastric remnant was observed. In the Billroth II patients, the presence of a 10 cpm component correlated negatively with symptoms. .A Schaap HM; Smout AJ; Akkermans LM. .I 275163 .U 91007421 .S Gut 9101; 31(9):989-92 .M Adult; Aged; Cross-Sectional Studies; Endoscopy; Epidemiologic Methods; Female; Human; Male; Middle Age; Norway; Peptic Ulcer/*EP; Sex Factors. .T Towards a true prevalence of peptic ulcer: the Sorreisa gastrointestinal disorder study. .P JOURNAL ARTICLE. .W This study, designed to overcome methodological problems inherent in earlier prevalence studies of peptic ulcer, was carried out in a municipality in northern Norway. It included the total population of 2027, aged 20-69 years, and comprised a questionnaire and search for previously diagnosed peptic ulcers in the local medical records for all subjects, and additional endoscopy of all subjects with dyspepsia and their matched healthy controls (n = 619). The overall prevalence was 10.5% in men and 9.5% in women, a sex ratio close to one and a higher duodenal:gastric ratio than previously reported from this region. A substantial 1% prevalence of asymptomatic ulcers was also observed. .A Bernersen B; Johnsen R; Straume B; Burhol PG; Jenssen TG; Stakkevold PA. .I 275164 .U 91007422 .S Gut 9101; 31(9):993-6 .M Adult; Case-Control Studies; Cereals; Dietary Carbohydrates/*AD/AE; Dietary Fiber/*AD/AE; Duodenal Ulcer/*EP/ET; Female; Human; Male; Middle Age; Risk Factors; Smoking/AE; Socioeconomic Factors; Support, Non-U.S. Gov't; Vegetables. .T Duodenal ulcer and refined carbohydrate intake: a case-control study assessing dietary fibre and refined sugar intake [see comments] .P JOURNAL ARTICLE. .W An association between duodenal ulceration and a low fibre intake and a high refined carbohydrate diet has been reported. We therefore compared the current diet, smoking habits, social class, and possible other risk factors of 78 patients with duodenal ulcer and a community control group matched for age and sex. Logistic regression for matched sets was used to calculate the relative risks for successive quintiles of dietary fibre and sugar intake before and after adjustment for total calorie intake and for the possible confounding effect of other known risk factors. Relative risks did not differ materially or consistently for total dietary fibre or for the cereal moiety whether adjusted or not for calorie intake. By contrast, relative risks tended to be reduced with high vegetable fibre intake and with low refined sugar intake. After controlling for smoking and social class, both of which were associated with ulcer disease, and for relative weight (Quetelet's index), the relation between ulcer disease and low refined sugar intake persisted, while that with high vegetable fibre intake was reduced. The results of this study indicate that a lack of cereal or total fibre intake plays no part in duodenal ulcer development but that a low refined sugar intake may be a protective factor. .A Katschinski BD; Logan RF; Edmond M; Langman MJ. .I 275165 .U 91007423 .S Gut 9101; 31(9):997-8 .M Adipose Tissue/CH; Adult; Aged; Dietary Fats, Unsaturated/*AD; Duodenal Ulcer/*ET/ME; Fatty Acids/AN; Human; Linoleic Acids/*AD; Male; Middle Age. .T Duodenal ulcer is associated with low dietary linoleic acid intake. .P JOURNAL ARTICLE. .W It has been suggested that the falling incidence and virulence of duodenal ulcer is related to increased dietary polyunsaturated essential fatty acid intake. The adipose fatty acid profile, which closely reflects dietary intake, was measured in 35 men with chronic duodenal ulcer and 35 matched control men. The mean percentage of linoleic acid in adipose tissue was significantly lower in the ulcer group (10.0 (0.7) v 12.3 (0.7)%, p less than 0.01) and this difference was found in both smokers and non-smokers. This finding suggests that the diets of duodenal ulcer patients are deficient in linoleic acid and this could be of aetiological importance. .A Grant HW; Palmer KR; Riermesma RR; Oliver MF. .I 275166 .U 91007424 .S Gut 9101; 31(9):999-1002 .M Amoxicillin/*TU; Anti-Ulcer Agents/TU; Bismuth/*TU; Campylobacter Infections/*DT; Drug Resistance, Microbial; Drug Therapy, Combination; Duodenal Ulcer/*DT/ET; Human; Metronidazole/*TU; Organometallic Compounds/*TU. .T Adjuvant antibiotic therapy in duodenal ulcers treated with colloidal bismuth subcitrate. .P JOURNAL ARTICLE. .W Persistence of Helicobacter pylori after duodenal ulcer healing is associated with high rates of ulcer relapse. We compared colloidal bismuth subcitrate alone with CBS combined with one of four antibiotic regimens in the treatment of duodenal ulcers. Endoscopy and antral biopsies were performed before treatment and four weeks afterwards. Biopsy specimens were examined for histological evidence of gastritis and by Gram stain and culture for H pylori infection. Altogether 141 patients were allocated to one of five treatment groups. Giving CBS and metronidazole (400 mg tid for 7 days) with and without amoxycillin (500 mg tid) achieved higher clearance rates of H pylori than treatment with CBS alone (p less than 0.01). These two combinations also achieved higher rates of antral gastritis healing than CBS alone (p less than 0.01 and p less than 0.05 respectively). Susceptibility to metronidazole was tested in 29 isolates before and in seven isolates after treatment with metronidazole by disc diffusion test and minimum inhibitory concentration assay. Twenty seven (93%) of the isolates were sensitive before treatment while six of seven (86%) were resistant afterwards. Four of the six resistant strains had acquired resistance during treatment and one of these had acquired metronidazole resistance despite concomitant treatment with amoxycillin, to which it remained sensitive. CBS with adjuvant metronidazole at a dose of 400 mg tid for seven days significantly improves the eradication of H pylori compared with CBS alone. Acquired metronidazole resistance, however, seems to be an important cause of failure to eradicate H pylori. .A O'Riordan T; Mathai E; Tobin E; McKenna D; Keane C; Sweeney E; O'Morain C. .I 275167 .U 91007642 .S Hepatology 9101; 12(3 Pt 2):1S-244S .M Bile/*ME; Biological Transport; Cholesterol/*ME; Human; Precipitation; Support, Non-U.S. Gov't. .T Proceedings of the workshop on Frontiers in Gallstone Formation. Biliary cholesterol transport and precipitation. Warrenton, Virginia. April 16-19, 1989. .P CONGRESS; OVERALL. .I 275168 .U 91007643 .S Hepatology 9101; 12(3 Pt 2):1S-5S .M Animal; Bile/*ME/SE; Biological Transport; Cholelithiasis/*ET; Cholesterol/*ME; Crystallization; Human; Precipitation; Time Factors. .T Biliary cholesterol transport and precipitation: introduction and overview of conference. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Cholesterol is secreted into bile as cholesterol-phospholipid vesicles. The cholesterol and phospholipid are subsequently exposed to the bile salts contained in the bile, which leads to the process of micellation. Two situations may arise depending on whether there is enough bile salt in proportion to cholesterol to complete this "maturation" process. If the cholesterol saturation is low, at equilibrium the bile salts will have completely micellized the vesicles. On the other hand, if bile is saturated with cholesterol, the micellation process is incomplete and vesicles and micelles will be present at equilibrium. The residual vesicle in this latter situation may have a higher cholesterol/phospholipid ratio because of the greater propensity of phospholipid to be micellized. This situation may result in cholesterol nucleation. The mechanism of nucleation from vesicles and the possible role of nucleating and antinucleating proteins in this process have been discussed. .A Strasberg SM; Harvey PR. .I 275169 .U 91007644 .S Hepatology 9101; 12(3 Pt 2):106S-112S .M Bile/*ME; Electron Probe Microanalysis; Evaluation Studies; Micelles; Microscopy/MT; Microscopy, Electron; Models, Biological/*; Nuclear Magnetic Resonance; Support, U.S. Gov't, P.H.S.. .T Detection of vesicles in native and model biles by morphological and other structural techniques: applications and limitations. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Detection and characterization of vesicles in native and model biles can be achieved by both imaging and nonimaging methods. Imaging methods provide more directly interpretable information, but sample preparation problems, particularly for application of electron microscopy, are a source of serious concern. Several nonimaging methods have also been used to advantage in the study of vesicles. These methods all share the disadvantage of being model dependent, thus making data analysis indirect and inferential; this is in addition to constraints unique to each of the several nonimaging methods. It is suggested that to achieve optimal accuracy in vesicle studies, a combination of different structural methods should be used where possible. .A Holzbach RT. .I 275170 .U 91007645 .S Hepatology 9101; 12(3 Pt 2):113S-121S; discussion 121S-122S .M Bile/*ME; Chemistry, Physical; Lasers/*DU; Models, Biological/*; Scattering, Radiation; Support, U.S. Gov't, P.H.S.. .T Principles of laser light-scattering spectroscopy: applications to the physicochemical study of model and native biles. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W We present a nonmathematical treatment of the theoretical and experimental aspects of modern laser light-scattering techniques. We also describe the design of a "home-built" laser light-scattering apparatus used in the authors' laboratory for the physicochemical study of model and native biles. These powerful techniques provide nonperturbing measurements of the sizes, polydispersities and, in suitable cases, concentrations and shapes of simple micelles, mixed micelles, vesicles and large proteins in bile. the sizes of these aggregates (10 to 2,000 A) fall within limits resolvable by laser light and are conventionally expressed as mean hydrodynamic radii, Rh. Static light-scattering measurements of biliary lipid aggregates provide molecular weights and important information concerning particle shape, whereas quasielastic (also referred to as dynamic) light-scattering measurements assess particle sizes and polydispersities. Under favorable circumstances, quasielastic light scattering allows simultaneous determinations of sizes and concentrations of coexisting particle populations. The use of laser light-scattering technology in solving the solution properties and the physicochemical structures of model and native biles is detailed. In view of the extraordinarily diverse backgrounds of researchers in the gallstone field (e.g., internists, surgeons, biochemists, physicists), we believe that the present article (which relies heavily on graphical representations) will afford a better understanding of the usefulness and limitations of laser light-scattering techniques, particularly in their applications to the study of bile. .A Cohen DE; Fisch MR; Carey MC. .I 275171 .U 91007646 .S Hepatology 9101; 12(3 Pt 2):123S-128S; discussion 128S-129S .M Bile/*ME; Bile Acids and Salts/ME; Carrier Proteins/ME; Cholesterol/ME; Chromatography; Chromatography, Gel/*; Human; Light/*; Micelles; Osmolar Concentration; Scattering, Radiation/*; Ultracentrifugation. .T Gel filtration and quasielastic light scattering studies of human bile. .P JOURNAL ARTICLE. .W Analyses of cholesterol carriers in the extremely variable biliary samples were performed by chromatography under standard conditions. Sephacryl columns were eluted with buffer containing 10 mmol/L sodium cholate, 150 mmol/L sodium chloride, 50 mmol/L Tris(hydroxymethyl)aminomethane-hydrochloride, pH 8.0, and 1.5 mmol/L ethylenediaminetetraacetate. Moderate changes in temperature, flow rate or sample size produced only minor differences in the results. Increments in bile salt concentration in the elution buffer caused progressive disappearance of vesicles and a rise in their cholesterol/phospholipid ratio. Using the standard chromatographic technique, analyses of the same bile gave reproducible results, and comparisons among various biles were possible. Quantitative light scattering measurements of bile showed that the amount of vesicular cholesterol in whole unprocessed bile was similar to that measured by Sephacryl chromatography. Analyses of human gallbladder biles using a high-resolution Sephacryl column showed four cholesterol-containing peaks: vesicles, lamellae, mixed micelles and an undefined carrier. This long chromatographic column separated the lamellar from the micellar peaks (which had merged on the short column). Phospholipid lamellae solubilized most of the biliary cholesterol. These findings were confirmed by ultracentrifugation of bile. .A Somjen GJ; Rosenberg R; Gilat T. .I 275172 .U 91007647 .S Hepatology 9101; 12(3 Pt 2):130S-133S .M Bile/*ME; Carrier Proteins/*ME; Cholesterol/ME; Evaluation Studies; Human; Hydrostatic Pressure; Metrizamide/DU; Support, Non-U.S. Gov't; Time Factors; Ultracentrifugation/*MT. .T Separation and quantitation of cholesterol carriers in native bile by ultracentrifugation. .P JOURNAL ARTICLE. .W The vesicular and micellar carriers of biliary cholesterol were isolated and quantitated from native bile by a simple and short isopyknic ultracentrifugal method. The method was designed to decrease the potential pitfalls of classic ultracentrifugation: osmotic effects of the centrifugation media and hydrostatic pressure effects generated in the centrifuge tube. This was accomplished by using metrizamide as an inert centrifugation medium for isopyknic separation and a vertical rotor. The buoyant density of vesicles isolated from human native bile varied between 1.010 and 1.030 gm/ml, as determined in preformed bile-metrizamide density gradients after 285 min of centrifugation. When 16% metrizamide was directly dissolved in bile, its density increased to 1.060 gm/ml. After 120 min of centrifugation, it was found that more than 95% of total vesicular cholesterol floated at the top of the centrifuge tube. This fraction appeared as one or two white opalescent bands. The present ultracentrifugal method was validated by gel filtration chromatography. It was found that more than 95% of vesicular cholesterol migrated to the top 0.4 ml of the centrifuge tube after the short-run centrifugation. Approximately 5% of total biliary cholesterol present in the vesicular fractions was in fact solubilized in mixed micelles as assessed by gel filtration chromatography. Although the proportion of vesicles and micelles estimated with the present ultracentrifugal method is in the range reported by other authors using the more common chromatographic method, we believe that our method has two major advantages. First, it eliminates the dilutional effect of buffers necessary for gel filtration chromatography.(ABSTRACT TRUNCATED AT 250 WORDS) .A Amigo L; Covarrubias C; Nervi F. .I 275173 .U 91007648 .S Hepatology 9101; 12(3 Pt 2):134S-141S; discussion 141S-142S .M Animal; Bile/*SE; Bile Acids and Salts/BL; Biological Transport; Cholesterol/SE; Human; Lipids/*SE; Liver/CY/*SE; Liver Circulation; Models, Biological; Support, Non-U.S. Gov't. .T Secretion of biliary lipids from the hepatocyte. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W A significant amount of biliary cholesterol is carried in unilamellar-phospholipid (lecithin) vesicles, in both supersaturated human hepatic bile and unsaturated rat bile. This fact supports the concept that biliary cholesterol is normally secreted in phospholipid vesicles from the hepatocyte into the canaliculus. The fundamental aspects of biliary lipid secretion relate first to the quantitative determinants of hepatocytic cholesterol secretion into the bile and, second, to the cell biology of this process. There is a tight curvilinear coupling between the rates of bile acids and biliary lipid secretion in all animal species. The hydrophobicity of the bile acid pool may modify this cosecretory mechanism in that more hydrophobic bile acids recruit more phospholipid and cholesterol per mole of bile acid secreted into the bile. The quantitative significance of this effect, however, is relatively minor. In contrast, intrahepatic determinants, such as the rates of hepatic cholesterol esterification and very low density lipoprotein production modulated by dietary factors, may markedly change the amount of cholesterol carried in vesicles into the bile. Recent studies provide strong evidence to support the concept that biliary cholesterol output is also modulated by the amount of free cholesterol available in specific regions of the endoplasmic reticulum for recruitment by the bile acid cosecretory mechanism. The origin of biliary lipids is in the smooth endoplasmic reticulum membranes. The intracellular transport and the canalicular secretory mechanism of the precursor of biliary lipid vesicles is mostly unknown. Two theories related to the cell biology of biliary lipid secretion are discussed in this article, the fusion-budding model and the exocytotic model. .A Marzolo MP; Rigotti A; Nervi F. .I 275174 .U 91007649 .S Hepatology 9101; 12(3 Pt 2):143S-147S; discussion 147S-148S .M Animal; Bile/*ME; Chemistry, Physical; Gallbladder/PH; Human; Lipids/*ME; Micelles; Models, Biological; Support, U.S. Gov't, P.H.S.. .T Physical chemistry of biliary lipids during bile formation. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Present concepts suggest that the canalicular secretion of bile salts is monomeric, which in turn drives the hepatic secretion of lecithin and cholesterol presumably as unilamellar vesicles into bile. As biliary lipids are concentrated within the biliary tree and gallbladder, bile salts structurally alter lecithin-cholesterol vesicles to form a variety of metastable aggregates whose structures and phase transformations are predicted by phase equilibria considerations. These structural transformations ultimately result in the dispersion of biliary lipids as thermodynamically stable micelles or micelles plus thermodynamically unstable vesicles in common duct and gallbladder biles. The experiments reviewed herein represent experimental simulations of these processes. We used pure aqueous lipid systems to model the putative stages of biliary lipid aggregation on the basis of interactions of small unilamellar vesicles of lecithin-cholesterol with bile salts as the latter's concentrations were varied from below to well above the critical micellar concentration. With submicellar bile salt concentrations likely to be found within hepatocytes, vesicle structures are not appreciably altered. However, perimicellar bile salt concentrations possibly occurring in canaliculi and bile ductules induce the formation of a hexagonal rodlike phase. On further increases in bile salt concentration, the hexagonal rods (formed from lecithin-rich and cholesterol-poor vesicles) are dissolved into mixed micelles as bile salt concentrations exceed their critical micellar concentrations. In slightly cholesterol-"supersaturated" biles, the rapid dissolution of this intermediate phase results in the formation of cholesterol-supersaturated mixed micelles that, in time, give rise to a new population of cholesterol-rich vesicles that coexist with saturated micelles.(ABSTRACT TRUNCATED AT 250 WORDS) .A Cohen DE; Carey MC. .I 275175 .U 91007650 .S Hepatology 9101; 12(3 Pt 2):149S-153S; discussion 153S-154S .M Bile Acids and Salts/*PD; Cholesterol/*; Micelles; Models, Biological; Phosphatidylcholines/*; Solubility. .T Stability of mixed micellar systems made by solubilizing phosphatidylcholine-cholesterol vesicles by bile salts. .P JOURNAL ARTICLE. .W Complete solubilization of phosphatidylcholine and cholesterol by bile salts in the form of stable mixed micelles requires that the effective ratio of bile salt/lipids in the mixed micelles (Re = ([bile salt] - critical micellar concentration)/([phosphatidylcholine] + [cholesterol]) will exceed a critical value. This equilibrium solubilizing ratio is an increasing function of the cholesterol/phosphatidylcholine ratio. In contrast, the concentration of sodium cholate required for solubilization of vesicles made of phosphatidylcholine and cholesterol does not increase by increasing the cholesterol/phosphatidylcholine ratio. Consequently, the latter solubilization procedure yields metastable mixed micelles whenever the cholate concentration is higher than that required for vesicle solubilization but lower than that needed for establishing a micellar equilibrium. These metastable mixed micelles undergo partial revesiculation to form cholesterol-rich vesicles that subsequently aggregate. Cholesterol crystallization appears to occur through its reorganization within these aggregated vesicles. The overall rate of the above series of processes increases sharply with the total lipid concentration and with the cholesterol/phosphatidylcholine ratio. The dependence of the rate on the effective ratio of bile salts/lipids is very complex: at any given ratio of cholesterol/phosphatidylcholine within the range of 0.3 to 0.5, increasing the cholesterol/phosphatidylcholine ratio requires higher cholate concentrations for the formation of stable mixed micelles (higher equilibrium solubilizing ratio). On the other hand, the metastable mixed micellar larsystems are long-lived whenever the effective ratio of cholate/lipids is lower than a critical value.(ABSTRACT TRUNCATED AT 250 WORDS) .A Lichtenberg D; Ragimova S; Bor A; Almog S; Vinkler C; Peled Y; Halpern Z. .I 275176 .U 91007651 .S Hepatology 9101; 12(3 Pt 2):155S-159S; discussion 159S-161S .M Animal; Bile/*ME; Cholesterol/*ME; Crystallization; Human; Micelles; Nomenclature; Support, U.S. Gov't, P.H.S.. .T Nucleation of cholesterol crystals in native bile. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Any substance capable of ultimately forming itself into a solid crystal must undergo an initial step of forming crystal nuclei. The nucleation step in crystallization for all such systems has been a difficult process to describe. Even the definition of what constitutes a "nucleus" remains elusive because one is dealing with a conceptual construct that is found only in the submicroscopic domain and therefore is inaccessible to direct measurement. Based on these considerations, the so-called nucleation time assay can at best only be taken as an empirical parameter. Nucleation (operationally defined) and growth of cholesterol monohydrate crystals in both model and native biles occurs rapidly after aggregation of supersaturated vesicles. Cholesterol made available for crystal growth also originates from the vesicular pathway and not directly from biliary micelles. The exact mechanism(s) governing this linked "precursor-product" relationship remains undefined. .A Holzbach RT. .I 275177 .U 91007652 .S Hepatology 9101; 12(3 Pt 2):17S-22S; discussion 22S-25S .M Bile/*PH/SE; Bile Acids and Salts/AI/BI/*SE; Bile Canaliculi/SE; Biotransformation; Human; Liver/CY/ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Bile acid secretion, bile flow and biliary lipid secretion in humans. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W The transport of bile acids through the hepatocyte and the effect of this flux of molecules on bile flow, biliary lipid secretion and bile acid biosynthesis are reviewed. Efficient hepatic clearance of bile acids involves several active systems and passive uptake. Formation of coenzyme A derivatives prevents reflux of lipophilic dihydroxy bile acids. Biotransformation of bile acids during hepatocyte transport involves both type I and type II biotransformations. The major type II biotransformation is reamidation of unconjugated bile acids, but sulfation and glucuronidation also occur. The only major type I biotransformation is oxidoreduction, which converts iso- or 3 oxo bile acids to the preferred 3 alpha-hydroxy form and 7 oxo bile acids to their corresponding 7 alpha-hydroxy derivatives. Secretion of bile acids into the canaliculus is concentrative and induces osmotic flow of plasma water and solutes across the paracellular junctions between the space of Disse and the canaliculus. Bile flow in man is characterized by its low volume and by a paucity of bile acid-independent flow when compared with that of other mammals. Bile acid secretion also induces biliary lipid secretion, but some lipid secretion appears to be bile acid independent. The lipid vesicles secreted in human bile have a much higher cholesterol/phospholipid ratio than those of other mammals. During flow down the biliary tree, vesicles are solubilized by bile acid micelles, and Ca++ ions are complexed by bile acid monomers and micelles. However, the biochemical mechanisms and factors regulating biliary lipid secretion in man are poorly understood. .A Hofmann AF. .I 275178 .U 91007653 .S Hepatology 9101; 12(3 Pt 2):176S-180S; discussion 180S-182S .M Bile/*CH; Body Fluids/CH; Cholelithiasis/ME; Duodenum/CH; Gallbladder/CH; Human; Lipids/AN; Liver/CH; Reference Values; Specimen Handling/*/MT. .T Bile sampling, processing and analysis in clinical studies. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Obtaining a proper bile sample for investigative purposes is of utmost importance to obtain valid results. Bile can be collected by direct aspiration of the gallbladder, by duodenal intubation or by T-tube drainage. The optimal method of collection depends on the investigative question, as well as on the resources available to the investigator. The procedures for obtaining, processing and analyzing human bile (gallbladder and hepatic) are summarized, pointing out the disadvantages and pitfalls that may occur. .A Strasberg SM; Harvey PR; Hofmann AF. .I 275179 .U 91007654 .S Hepatology 9101; 12(3 Pt 2):183S-186S; discussion 186S-188S .M Animal; Chemistry; Cholelithiasis/ET; Cholesterol/PH; Crystallization; Gallbladder/*ME; Human; Models, Biological; Mucins/ME/*PH; Mucus/PH; Sciuridae; Support, U.S. Gov't, P.H.S.. .T Gallbladder mucin as a pronucleating agent for cholesterol monohydrate crystals in bile. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Mucin is a densely glycosylated macromolecule secreted by the gallbladder epithelium as the principal constituent of gallbladder mucus. Hypersecretion of gallbladder mucus occurs in response to a lithogenic diet in experimental animals, and mucus accumulates as a viscous gel within the gallbladder lumen before gallstone formation. In both animals and man, the initial stage of cholesterol gallstone formation, the nucleation of cholesterol monohydrate crystals, occurs within the mucus gel. Inhibition of mucus secretion with aspirin prevents gallstone formation in the cholesterol-fed prairie dog, indicating the importance of mucus in gallstone formation. Mucin contains domains that bind cholesterol and lecithin transported as vesicles in supersaturated bile. Furthermore, mucin accelerates the nucleation of cholesterol crystals in both supersaturated model and native biles. Binding of cholesterol-enriched vesicles to hydrophobic domains on the mucin protein core appears to be critical for the acceleration of cholesterol crystal nucleation by mucin. Further study of the structure and function of gallbladder mucin should help to elucidate the pathogenesis of cholesterol cholelithiasis. .A Smith BF. .I 275180 .U 91007655 .S Hepatology 9101; 12(3 Pt 2):189S-192S; discussion 192S-194S .M Cholelithiasis/BL/ME; Chromatography; Concanavalin A/DU; Electrophoresis, Polyacrylamide Gel; Gallbladder/ME; Glycoproteins/ME/*PH; Human; Liver/ME; Models, Biological; Molecular Weight; Reference Values. .T Nonmucous glycoproteins as pronucleating agents. .P JOURNAL ARTICLE. .W Cholesterol crystallization-promoting factors probably play an important role in the pathogenesis of gallstone disease. We have isolated one of the factors involved by using lectin-affinity chromatography. A potent promoting activity binds to concanavalin A-Sepharose. The activity is heat labile and sensitive to digestion by glycosidase but remarkably insensitive to proteases. The concanavalin A-binding pronucleator affects cholesterol solubilization in model bile in two ways. It induces a shift of cholesterol and phospholipid from the micellar to the vesicular phase but also interacts directly with cholesterol-phospholipid vesicles. The concanavalin A-binding protein fraction contains at least two different promoting factors with gel permeation molecular weights of about 150 kD and 5 kD, respectively. The higher molecular weight activity could be assigned to a protein with an apparent molecular weight of 130 kD. Concanavalin A-binding-promoting activity was present in bile from both patients with and without stones, indicating that it is a normal constituent of bile. However, the activity was strongly increased in bile from patients with multiple cholesterol gallstones, suggesting that it could play a key role in gallstone formation in these patients. .A Groen AK. .I 275181 .U 91007656 .S Hepatology 9101; 12(3 Pt 2):195S-198S; discussion 199S .M Bile/*ME; Cholesterol/ME; Chromatography, Affinity; Crystallization; Crystallography/MT; Human; Proteins/ME/*PH; Spectrophotometry/MT; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Crystal growth-inhibiting proteins in bile. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W The idea that biliary proteins somehow inhibit nucleation/crystal growth of cholesterol crystals in supersaturated human biles is not new, and some supportive, albeit preliminary, evidence has already been provided for this. Progress in purification of biliary effector proteins has been slow and hindered by the lack of a sensitive and convenient assay method. The formidable problems of removing large amounts of both mucin and lipids from the samples before isolation of biliary proteins has constituted another major obstacle. Recently, the combination of a newly developed nucleation and crystal growth assay and the systematic use of lectin affinity chromatography has enabled rapid progress to be made. With these approaches, glycoprotein fractions containing primarily inhibiting activity and other fractions containing primarily promoting activity have been isolated from normal human biles. Thus these opposing activities can coexist and influence a balance of effects potentially defining the presence of health or disease. The most recent studies have led to the isolation of a single glycoprotein having an extremely potent crystal growth-inhibiting activity. .A Busch N; Holzbach RT. .I 275182 .U 91007657 .S Hepatology 9101; 12(3 Pt 2):200S-203S; discussion 203S-205S .M Animal; Bile/ME; Biliary Tract Diseases/DI/*ET/ME; Cholesterol/ME; Crystallization; Gallbladder/ME; Gallbladder Diseases/DI/ME; Human; Models, Biological; Particle Size; Precipitation; Support, U.S. Gov't, Non-P.H.S.; Ultrasonography. .T Pathogenesis of biliary sludge. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W The increasing application of ultrasonography in biliary tract disease had led to more frequent recognition of an old disorder--"biliary sludge." Sludge is detected on ultrasound as low-amplitude echoes without acoustic shadowing. It layers in the most dependent part of the gallbladder and shifts with positioning. Particulate matter in bile, such as cholesterol monohydrate crystals, has been shown to be echogenic. Agglomeration of these crystals in biles with high mucus content accounts for the layering and the characteristic appearance of the movement of sludge with alteration in patient position. Within the gallbladder, the stability of the vesicular form of cholesterol and protein-lipid interactions are important determinants of cholesterol precipitation. In mixed and pigment gallstones, the equilibrium between ionized and unionized calcium and the hydrolysis of conjugated bilirubin are also important factors. Although the risk factors contributing to the formation of gallbladder sludge have not been critically examined, it is now known that in some instances sludge can produce biliary pain and can be associated with acalculous cholecystitis, recurrent pancreatitis and, ultimately, the formation of gallstones. A better appreciation of the pathogenesis of sludge formation can help in the understanding of the genesis of gallstones and also perhaps in understanding other documented but poorly understood biliary and pancreatic disorders. .A Lee SP. .I 275183 .U 91007658 .S Hepatology 9101; 12(3 Pt 2):206S-214S; discussion 214S-218S .M Animal; Bile/*ME/PH; Biophysics; Calcinosis/CO/ET; Calcium/*ME/PH; Chemistry, Physical; Cholelithiasis/CO/*ET; Human; Models, Biological; Osmolar Concentration; Solubility; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Thermodynamics. .T Biliary calcium and gallstone formation. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W The purpose of this paper is to present a brief overview of the current status of the field of biliary calcium and the role of calcium in the formation and maturation of gallstones. The study of free Ca+(+) ions in bile by electrochemical potentiometric measurements using Ca+(+)-selective ion-exchange electrodes is a relatively new field, but much progress has been made in the past few years. Using this powerful analytical tool, new concepts and findings have arisen in almost every aspect of biliary calcium. Although the current symposium is targeted primarily toward cholesterol gallstones, there are several areas in which understanding of biliary calcium may significantly contribute to a better understanding of the pathogenesis of cholesterol, as well as "pigment" (calcium salt), gallstones. Five broad areas are considered in relation to biliary calcium: (a) physiology (calcium entry into bile), (b) biophysics (the regulation of biliary free [Ca+(+)] as related to Gibbs-Donnan equilibria, (c) physical chemistry (the physicochemical state of calcium in bile, (d) thermodynamics (calcium solubility in bile), and (e) kinetics (pronucleating and antinucleating factors and metastable states). With more specific reference to cholesterol stones, consideration is also made of (a) the calcium salt "seed" hypothesis in cholesterol stone pathogenesis; (b) the interactions of Ca+(+) with phospholipid-cholesterol vesicles, with consideration of possible structural requirements and (c) thermodynamic and kinetic factors as related to peripheral or "eggshell" calcification of existing cholesterol stones. .A Moore EW. .I 275184 .U 91007659 .S Hepatology 9101; 12(3 Pt 2):219S-224S; discussion 224S-226S .M Animal; Bile/ME; Bilirubin/*ME; Cholelithiasis/*ET/ME; Cholesterol/*ME; Crystallization; Human; Solubility; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Water. .T Unconjugated bilirubin and cholesterol gallstone formation. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Cholesterol gallstones usually have small amounts of pigment at their centers and often have diffuse pigmentation or pigmented layers alternating with cholesterol layers and/or pigmented rims associated with calcium carbonate (eggshell calcification). The pigments are primarily monomeric calcium salts of unconjugated bilirubin anions and/or an insoluble, black, network polymer of tetrapyrroles. Bilirubin presumably can precipitate only if bile is supersaturated with calcium bilirubinates. Among various in vitro model systems, the aqueous solubilities and pK'a values for unconjugated bilirubin differ greatly. It is therefore not known whether normal bile is saturated with unconjugated bilirubin. However, all systems indicate that unconjugated bilirubin is solubilized by binding to bile salt monomers and oligomers, as well as micelles; marked metastable supersaturation of unconjugated bilirubin can occur in the presence of bile salt micelles, and both pK'a values of unconjugated bilirubin are greater than 6.0, probably because of internal hydrogen-bonding of the--COOH groups. Lecithin decreases equilibrium solubilization of unconjugated bilirubin crystals but enhances metastable supersaturation of unconjugated bilirubin. Calcium ions form insoluble salts with unconjugated bilirubin monoanions and dianions but soluble complexes with bilirubin conjugates. The solubility products of the calcium bilirubinate salts suggest that normal hepatic bile is not saturated with CaB or Ca(HB)2 but that gallbladder bile may be supersaturated with Ca(HB)2.(ABSTRACT TRUNCATED AT 250 WORDS) .A Ostrow JD. .I 275185 .U 91007660 .S Hepatology 9101; 12(3 Pt 2):26S-31S; discussion 31S-32S .M Biological Transport; Cholelithiasis/*ET; Cholesterol/*ME; Crystallization; Human; Support, U.S. Gov't, P.H.S.. .T Current concepts of cholesterol transport and crystal formation in human bile. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W The presence of vesicles in human bile probably accounts almost entirely for the frequently observed, but hitherto unexplained, phenomenon of metastable cholesterol supersaturation. This, in turn, largely explains the prolonged stability of cholesterol solubilized in supersaturated human bile. Under certain overall compositional conditions for a supersaturated native bile, the vesicular phase in its contribution to total cholesterol transport also becomes supersaturated in cholesterol. Because of this, the vesicles also become unstable, leading to formation of cholesterol crystals. A simple but common example of one factor affecting composition in this way is concentration of total solutes, especially the biliary lipids. Conversely, dilution of bile (e.g., hepatic bile) markedly reduces the cholesterol saturation level in biliary vesicles. The result is that such vesicles become much more stable. Under these conditions, cholesterol crystal formation becomes unlikely and rarely, if ever, occurs. .A Holzbach RT. .I 275186 .U 91007661 .S Hepatology 9101; 12(3 Pt 2):33S-37S; discussion 37S-38S .M Bile/*ME; Bile Acids and Salts/ME; Chemistry; Cholesterol/ME; Crystallography; Human; Lipids/*ME; Micelles; Molecular Conformation; Phospholipids/ME. .T Structural studies of the lipid components of bile. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W The lipid-rich molecular aggregates responsible for the transport of cholesterol in bile include mixed micelles and bilayer vesicles. In this review, the molecular conformations of the individual lipid components of biliary micelles and vesicles (phospholipids, bile salts and cholesterol) obtained by high-resolution x-ray crystallographical analysis are described. The key conformational/packing features relevant to lipid organization, molecular interactions and cholesterol solubility in bile are discussed. The structure of cholesterol monohydrate, the major component in cholesterol gallstones, is described and problems relevant to cholesterol crystal nucleation/growth processes are briefly discussed. .A Shipley GG. .I 275187 .U 91007662 .S Hepatology 9101; 12(3 Pt 2):39S-44S .M Animal; Bile/*ME; Bile Acids and Salts/ME; Cholesterol/ME; Human; Light/*; Lipids/*ME; Micelles; Phosphatidylcholines/ME; Scattering, Radiation; Solutions. .T Quasielastic light scattering studies of aqueous biliary lipid systems and native bile. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W During the past 15 yr, the technique of quasielastic light scattering has been used by a number of laboratories to systematically investigate the aggregative behavior of model bile systems and more recently to characterize particles present in native bile. Quasielastic light scattering investigations of aqueous bile salt solutions have indicated important similarities and differences between the various bile salt species and have led to a quantitative model for the formation of globular and rodlike micelles, based on Small and Ekwall's primary-secondary micelle hypothesis. Studies of aqueous bile salt-lecithin systems have indicated three important aggregation regimens dependent on the lecithin/bile salt molar ratio and total solute concentration. Region I of the phase diagram, which includes the lecithin/bile salt and total solute concentration values found in most mammalian biles, corresponds to a population of "simple" bile salt micelles coexisting in equilibrium with a population of mixed bile salt-lecithin micelles. Region II contains only mixed micelles, whose apparent size and shape vary with lecithin/bile salt and total solute concentration in a manner consistent with a "mixed disc" model. In this model, bile salts not only coat the perimeter of the disc (as proposed in Small's original model) but are also incorporated within the lecithin bilayer, possibly as hydrogen-bonded dimers. Finally, in region III, where total solute concentration values are typically less than the critical micelle concentration of the pure bile salt, the systems contain mixed vesicles (spherical bilayer shells) whose size (approximately 130 to 500A) depends on lecithin/bile salt and total solute concentration in accordance with a simple partition equilibrium that determines the composition of the mixed vesicle bilayer.(ABSTRACT TRUNCATED AT 250 WORDS) .A Mazer NA. .I 275188 .U 91007663 .S Hepatology 9101; 12(3 Pt 2):45S-49S; discussion 49S-50S .M Bile Acids and Salts; Comparative Study; Dialysis/*MT; Evaluation Studies; Membranes, Artificial; Micelles; Osmolar Concentration; Phosphatidylcholines/*; Solutions; Support, U.S. Gov't, P.H.S.; Taurocholic Acid/*; Time Factors. .T Equilibrium dialysis studies on aqueous taurocholate-lecithin solutions: further validation of the method. .P JOURNAL ARTICLE. .W Since the 1980 publication by Mazer, Benedek and Carey on the concept of the simple micelle-mixed micelle coexistence phenomenon in the bile salt-lecithin systems, it became apparent that a reliable method was needed for measuring the coexisting species concentrations. We recently published a method based on membrane dialysis equilibrium, and the purpose of this report is to review and to validate this previous work. In the present studies, two dialysis membranes with molecular weight cut-off of 8,000 and 12,000 to 14,000 Da, respectively, and two sets of solution volume conditions were investigated with the taurocholate-lecithin system. Coexistence data were obtained over a wide range of lecithin concentrations and the results were found to be in good agreement with those from the previous studies. The bile salt/lecithin molar ratios for the mixed micelles were also deduced from the data. The principal conclusion of this study is that although there is a moderate amount of variability (10% to 15%), the method is both satisfactory and useful in studying bile salt-lecithin equilibria and dynamics. .A Higuchi WI; Liu CL; Adachi Y; Mazer NA; Lee PH. .I 275189 .U 91007664 .S Hepatology 9101; 12(3 Pt 2):51S-52S; discussion 53S-55S .M Chemistry; Lipid Bilayers; Micelles; Phosphatidylcholines/*ME; Suspensions; Water. .T Phosphatidylcholine vesicles: structure and formation. .P JOURNAL ARTICLE. .W Phosphatidylcholines and certain other phospholipids, as pure substances and as mixtures, can be dispersed in aqueous media to form unilamellar vesicles. The process by which these vesicles form in most instances depends on the bending and subsequent closure of an initially flat disc micelle. Under some circumstances this process can be reversed to generate disc micelles from vesicles. These processes may occur in the formation and nonequilibrium transformations of bile. .A Thompson TE. .I 275190 .U 91007665 .S Hepatology 9101; 12(3 Pt 2):56S-60S .M Chemistry; Cholesterol; Crystallization; Drug Stability; Lipid Bilayers; Membrane Fusion; Micelles; Phospholipids/*; Support, U.S. Gov't, P.H.S.; Surface Properties; Surface-Active Agents/PD. .T Surface chemistry of phospholipid vesicles relevant to their aggregation and fusion. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W A general description of those forces that are important in the stability of the lipid bilayer is presented. The analysis focuses on those that may change under conditions in which aggregation or fusion of vesicles or exchange of their molecules may occur. It is that class of membrane forces that is most likely to play a role in the process(es) that leads to the formation of cholesterol crystals in bile, which eventually grow into gallstones. A specific, hypothetical mechanism for cholesterol crystal nucleation based on vesicle fusion is also given. This mechanism is consistent with the principles of surface chemistry outlined. .A MacDonald RC. .I 275191 .U 91007666 .S Hepatology 9101; 12(3 Pt 2):6S-14S; discussion 14S-16S .M Animal; Bile/*ME; Bile Acids and Salts/ME; Chemistry; Human; Lipids/*ME; Phospholipids/ME; Reference Values; Sterols/ME; Support, U.S. Gov't, P.H.S.. .T Chemical species of lipids in bile. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Bile salts, phospholipids and sterols are the major lipid species in bile. The common bile salts possess a steroid nucleus of four fused hydrocarbon rings with polar hydroxyl functions and an aliphatic side chain conjugated in amide linkage with glycine or taurine. Since the ionized carboxylate or sulfonate group on the side chain renders bile salts water soluble, they are formally classified as soluble amphiphiles. The common bile salts differ in the number and orientation of the hydroxyl groups on the steroid nucleus. Bile salts synthesized from cholesterol in the liver are called primary bile salts, which in humans are cholate, with three hydroxyl groups, and chenodeoxycholate, with two hydroxyl groups. Secondary bile salts are created by the action of intestinal bacteria on primary bile salts; deoxycholate, with two hydroxyl groups, and lithocholate, with a single hydroxyl group, are formed from cholate and chenodeoxycholate, respectively. "Tertiary" bile salts are the result of modification of secondary bile salts by intestinal flora or hepatocytes; in humans these are the sulfate ester of lithocholate and ursodeoxycholate, the 7 beta-epimer of chenodeoxycholate. Lecithin (diacylphosphatidylcholine), the major phospholipid in bile, is an insoluble, swelling amphiphile with a hydrophilic, zwitterionic phosphocholine head group and hydrophobic tails comprised of two long fatty acyl chains. Biliary lecithin is derived from the least hydrophobic hepatic lecithins and typically contains a saturated C-16 acyl chain in the sn-1 position and an unsaturated C-18 or C-20 acyl chain in the sn-2 position. Cholesterol, present solely as the nonesterified free alcohol, accounts for more than 90% to 95% of the sterols in bile.(ABSTRACT TRUNCATED AT 250 WORDS) .A Hay DW; Carey MC. .I 275192 .U 91007667 .S Hepatology 9101; 12(3 Pt 2):61S-66S .M Animal; Bile/*SE; Cholelithiasis/ET; Fluorescence; Human; Lipids/*SE; Membrane Fusion/*; Membrane Lipids/ME; Methods; Solutions; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Fluorescence assays to monitor membrane fusion: potential application in biliary lipid secretion and vesicle interactions. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Membrane fusion constitutes an essential, intermediate step in numerous cell biological processes, occurring for example during endocytosis, membrane recycling and exocytosis. Also less desirable events such as the infection of cells by animal viruses are mediated by membrane fusion during which the viral envelope merges with a cellular membrane, causing the expulsion of the viral nucleocapsid into the cytoplasm of the cell as an initial step in virus replication. Much of our current knowledge concerning the mechanism of membrane fusion has been derived from studies using simple artificial membranes, such as liposomes or phospholipid vesicles, as model systems. A most essential feature of these studies has been the development of membrane fusion assays that register in a sensitive and continuous fashion the mixing of membranes or the aqueous volumes initially enclosed by these membranes. Not only do these assays allow one to readily detect and quantify fusion, but they also provide the possibility to relate the kinetics of fusion to the rate by which certain molecular changes in membranes take place. Obviously, this insight is of relevance for understanding the mechanism of membrane fusion. The principles and applications of some representative assays that rely on the use of fluorescence spectroscopy will be discussed. Assays that monitor membrane mixing are commonly based on the detection of changes in resonance energy transfer efficiency or the relief of fluorescence self-quenching of appropriate fluorescent lipid analogs. Contents mixing assays rely on either the formation of a (aqueous-soluble) fluorescent complex or quenching of a fluorophore, encapsulated in one vesicle population, by a suitable quencher, entrapped in a second population.(ABSTRACT TRUNCATED AT 250 WORDS) .A Hoekstra D. .I 275193 .U 91007668 .S Hepatology 9101; 12(3 Pt 2):67S-72S; discussion 72S-74S .M Animal; Anions/PD; Bile/*ME; Calcium-Binding Proteins/PD; Cations/ME/PD; Human; Lectins/PD; Lipids/ME; Liposomes/ME; Membrane Fusion/*PH; Membranes/ME; Models, Biological; Support, U.S. Gov't, P.H.S.. .T Molecular control of vesicle aggregation and membrane fusion: hypotheses on bile vesicles. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Molecular factors that control the aggregation and fusion of phospholipid vesicles are reviewed. These include membrane composition, vesicle size, various cations, membrane phase state, dehydrating agents and proteins. Several hypotheses are presented for the mechanism by which bile vesicles aggregate and fuse. It is proposed that phase-separated domains of cholesterol in the bile vesicle bilayer mediate the close approach of the vesicles and that molecular packing defects at the domain boundaries mediate hydrophobic interaction between and fusion of apposed membranes. The apposition or fusion of the membranes may provide the third dimension within which the cholesterol domains on apposed or collapsed membranes can begin to form the monohydrate crystal. Other mediators of aggregation and fusion are likely to be proteins that interact hydrophobically with the bile vesicle and diacylglycerol formed in the vesicles by phospholipase C action. Ca2+ is thought to enhance fusion by interacting with bile salts in the membrane or with membrane-associated proteins. .A Duzgunes N. .I 275194 .U 91007669 .S Hepatology 9101; 12(3 Pt 2):75S-80S; discussion 80S-82S .M Animal; Cholesterol/*/ME; Crystallization; Human; Lipid Bilayers; Phosphatidylcholines/*ME; Solubility; Support, U.S. Gov't, P.H.S.; Water. .T Cholesterol packing, crystallization and exchange properties in phosphatidylcholine vesicle systems. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W The properties of phosphatidylcholine/cholesterol vesicles have been studied extensively because of their relevance to the behavior of these components in cell membranes. At equilibrium, phosphatidylcholine bilayers are saturated when equimolar levels of cholesterol are incorporated; the cholesterol molecules interfere with the cooperative lateral interactions of the phosphatidylcholine acyl chains and restrict the fluidity relative to pure liquid-crystal phosphatidylcholine bilayers. Mixed cholesterol/phosphatidylcholine bilayers containing more than equimolar cholesterol are metastable; on storage excess cholesterol is released from the vesicles and forms cholesterol monohydrate crystals. This process models the formation of cholesterol gallstones in bile and the growth of the crystals probably involves, at least in part, diffusion of cholesterol molecules from the vesicle bilayer to the crystal surface. The cholesterol-phosphatidylcholine interaction energy in the lipid-water interface of the donor vesicle has a critical effect on the rate of this transfer process. .A Phillips MC. .I 275195 .U 91007670 .S Hepatology 9101; 12(3 Pt 2):83S-86S; discussion 86S-87S .M Bile Acids and Salts/*; Comparative Study; Kinetics; Micelles; Phospholipids/*/PH; Support, U.S. Gov't, P.H.S.. .T Comparison of spontaneous phospholipid transfer between phospholipid vesicles and between phospholipid-bile salt mixed micelles. .P JOURNAL ARTICLE. .W Fluorescent-labeled N-(7-nitro-2,1,3-benzoxadiazol-4-yl)phosphatidylethanolamine was used to compare the spontaneous rates of phospholipid transfer between phospholipid vesicles and between phospholipid-bile salt micelles. The half times for transfer between the mixed micelles are 200 to 6,000 times faster than between vesicles, depending on the acyl chain length of the N-(7-nitro-2,1,3-benzoxadiazol-4-yl)phosphatidylethanolamine and the total lipid concentration. A kinetic analysis of the rates of phospholipid transfer between vesicles indicated that transfer occurs predominantly as soluble monomers moving through the water phase. Transfer between mixed micelles was found to occur by the same aqueous diffusion mechanism at low lipid concentrations, but at high lipid concentrations, transfer occurs predominantly during transient micelle collisions. The faster rate of transfer between mixed micelles relative to vesicles results both from the collision-dependent transfer and from an increase in the rate-limiting step for aqueous diffusion-phospholipid dissociation from the micelle surface. The relative contribution of collision-dependent transfer to the overall transfer rate increases with phospholipid acyl chain length and total lipid concentration. For the phospholipid species and mixed micelle concentrations normally found in the biliary tract, the predominant mode of transfer is predicted to occur by the collision-dependent mechanism. .A Nichols JW. .I 275196 .U 91007671 .S Hepatology 9101; 12(3 Pt 2):88S-91S; discussion 91S-93S .M Bile/*ME; Cholesterol/*ME; Crystallization; Feasibility Studies; Models, Biological; Support, U.S. Gov't, P.H.S.; Thermodynamics; Time Factors. .T Cholesterol monomer activity and its role in understanding cholesterol saturation and crystallization. .P JOURNAL ARTICLE. .W Cholesterol in bile has been linked to the incidence of gallstone disease through the concept of supersaturation as measured by the cholesterol saturation index. The latter is a linear function of cholesterol concentration and is based on the assumption that all cholesterol in bile is solubilized and transported in bile salt-lecithin mixed micelles and in bile salt simple micelles. In light of the discovery of the cholesterol-lecithin vesicles as significant cholesterol carriers, there is a need to reevaluate this old concept. This study examined the feasibility of the silicone polymer uptake method for the direct determination of the cholesterol thermodynamic activity in model bile systems. In cases of unsaturation and near saturation, a linear relationship was observed between the cholesterol concentration in the silicone polymer at equilibrium and the cholesterol saturation index (the cholesterol concentration in the aqueous micellar solution at equilibrium/cholesterol monohydrate solubility in the same medium) for taurocholate and taurochenodeoxycholate systems either containing or not containing lecithin. In taurocholate-lecithin solutions supersaturated with cholesterol, the linear relationship continued to hold up to the point where vesicles started to form. Vesicle formation initiated a negative deviation from linearity. At constant lecithin concentration, the cholesterol thermodynamic activity at which vesicle formation began was a function of the taurocholate/lecithin ratio; the larger the taurocholate/lecithin ratio, the higher the cholesterol thermodynamic activity for the onset of vesicle formation.(ABSTRACT TRUNCATED AT 250 WORDS) .A Higuchi WI; Lee PH; Takayama K; Jain UK; Mazer NA. .I 275197 .U 91007672 .S Hepatology 9101; 12(3 Pt 2):94S-104S; discussion 104S-105S .M Animal; Bile/*ME; Bile Acids and Salts; Carrier Proteins/*AN; Cholesterol/ME; Human; Methods; Micelles; Models, Biological; Osmolar Concentration; Phosphatidylcholines; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Water. .T Separation and quantitation of cholesterol "carriers" in bile. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W On the basis of phase equilibria theory and experimental data, we discuss the identity, separation and quantitation of cholesterol-solubilizing lipid aggregates in bile, trivially known as cholesterol "carriers." We first describe analogies (as well as lack of correspondence) between equilibrium phase diagrams of aqueous bile salt, lecithin and cholesterol systems and phase equilibria in native biles. At equilibrium, the possible number and types of different cholesterol "carriers" are limited by constraints placed by the phase rule. These "carriers" include simple micelles (bile salts without lecithin), mixed micelles (bile salts plus lecithin), a lecithin plus cholesterol lamellar phase composed of single bilayer structures (vesicles) or multilamellar structures (liquid crystals) and possibly fragments of a hexagonal phase. Clearly, in this context, cholesterol monohydrate crystals, no matter how small, cannot be considered "carriers." We also use a metastable "phase diagram" for aqueous taurocholate-egg yolk lecithin-cholesterol systems to interpret physicochemical studies on the formation and stability of native biles. In biliary lipid systems, bile salt monomers with or without simple bile salt micelles are present in the aqueous "phase" in equilibrium with mixed micelles/or vesicles. This bile salt concentration is designated the intermicellar concentration but actually represents the total nonmixed micellar/nonvesicular concentration of bile salts (i.e., bile salt monomers and simple bile salt micelles when present) and may be a value that falls below, equal to or above the critical micellar concentration of the bile salts. Experimental estimates of the intermicellar-intervesicular bile salt concentration in model systems are compared with the range of bile salt concentrations that has been used in the literature to separate the presently accepted cholesterol "carriers" (mixed micelles and vesicles) in both model and native biles. We also reinterpret published lipid compositions of phases separated from human bile, using both a nonequilibrium "phase diagram" and an equilibrium phase diagram for the model system, taurocholate-egg yolk lecithin-cholesterol. From these analyses, we conclude that precise quantitation of cholesterol "carriers" in bile awaits methods to accurately determine the intermicellar-intervesicular concentration of bile salts in any individual bile, as well as advances in nonperturbing separatory procedures, and methods to control the thermal and temporal history of native bile samples. .A Donovan JM; Carey MC. .I 275198 .U 91007673 .S Hepatology 9101; 12(4 Pt 1):633-7 .M Alcohol, Ethyl/*AI; Animal; DNA/BI; Enzyme Induction/DE; Hepatectomy; Liver/ME; Liver Regeneration/*DE; Male; Ornithine Decarboxylase/BI; Polyamines/ME; Putrescine/*PH; Rats; Rats, Inbred WF; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Thymidine/ME; Time Factors. .T Supplemental putrescine reverses ethanol-associated inhibition of liver regeneration. .P JOURNAL ARTICLE. .W Biosynthesis of the polyamines, putrescine, spermidine and spermine, is required for DNA synthesis and liver regeneration after partial hepatectomy. Chronic ethanol consumption impairs polyamine synthesis during the prereplicative phase after partial hepatectomy. To determine whether this delay in polyamine synthesis contributes to ethanol's inhibition of liver regeneration, the ability of supplemental putrescine to improve regeneration in ethanol-fed rats was tested. Chronically ethanol-fed rats and isocalorically maintained controls underwent partial hepatectomy and were injected intraperitoneally with saline or putrescine (0.03 or 0.30 mmol/kg) at 0, 4, 8 and 12 hr after partial hepatectomy. Rats were killed at 24, 48 or 72 hr, 1 hr after exposure to [3H]thymidine, so that DNA synthesis could be estimated. DNA synthesis was significantly inhibited in ethanol-fed rats treated with saline compared with saline-treated pair-fed controls. Supplemental putrescine did not affect DNA synthesis in pair-fed rats. In contrast, putrescine significantly improved [3H]thymidine incorporation 24 to 72 hr after partial hepatectomy in ethanol-fed rats. Intraperitoneal injection of putrescine (1.2 mmol/kg) at the time of partial hepatectomy increased hepatic polyamine concentrations for the first 6 hr after partial hepatectomy despite significantly inhibiting the activity of ornithine decarboxylase, the rate-limiting enzyme for polyamine synthesis, in both groups. Hepatic polyamine levels after putrescine injection were greater in ethanol-fed rats than in similarly treated controls. These data suggest that putrescine treatment triggers events that normalize DNA synthesis in ethanol-fed rats. These results confirm the hypothesis that ethanol's antiregenerative mechanism intimately involves inhibition of putrescine synthesis. .A Diehl AM; Abdo S; Brown N. .I 275199 .U 91007674 .S Hepatology 9101; 12(4 Pt 1):638-43 .M Antigens, Viral/*AN; Hepatoma/*MI; Human; Liver Neoplasms/*MI; Neuraminidase/PD; Rotaviruses/*GD/IM; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Trypsin/PD; Tumor Cells, Cultured. .T Growth of group A rotaviruses in a human liver cell line. .P JOURNAL ARTICLE. .W Recent observations in children with rotavirus gastroenteritis and in infant mice given rotavirus vaccine by oral administration suggest that this well-known gastrointestinal pathogen may infect the liver. To examine this possibility, the susceptibility of Hep G2 cells to infection with a variety of rotavirus strains was tested. These cells were used because they are considered to be well differentiated and exhibit many liver-specific functions. The Hep G2 cells supported the growth of the simian strain rhesus rotavirus (MMU 18006), a strain currently being used in vaccine trails, but did not support the growth of any human strain (D, DS1, Price or ST3). The rhesus rotavirus infection was cytopathic and resulted in release of lactate dehydrogenase. Rhesus rotavirus growth in Hep G2 cells displayed trypsin-enhanced infectivity and was inhibited by pretreatment of cells with Arthrobacter ureafaciens neuraminidase but not with neuraminidase from Clostridium perfringens. Hep G2 cells were also permissive for another simian strain (SA11), a bovine strain (UK) and single gene substitution reassortants containing VP7 (the major outer capsid neutralization protein) from a human rotavirus strain and the remaining 10 genes from either rhesus rotavirus or UK. In general, UK and its reassortants produced lower levels of antigen than did rhesus rotavirus and its reassortants. Hep G2 cells and other hepatic cell lines may prove to be useful tools to explore the hepatotropic potential of wild-type rotaviruses and candidate vaccine strains. .A Schwarz KB; Moore TJ; Willoughby RE Jr; Wee SB; Vonderfecht SL; Yolken RH. .I 275200 .U 91007675 .S Hepatology 9101; 12(4 Pt 1):644-52 .M Animal; Cell Division; Dinoprostone/BI/*PH; Down-Regulation (Physiology); Female; Indomethacin/PD; Interferon Type I/AI/BI/*PH; Killer Cells, Lymphokine-Activated/*CY; Kupffer Cells/*ME; Liver/CY/*ME; Mice; Mice, Inbred C57BL; Prostaglandin D2/PD; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Suppression of hepatic lymphokine-activated killer cell induction by murine Kupffer cells and hepatocytes. .P JOURNAL ARTICLE. .W Murine lymphokine-activated-killer cell activity was readily induced by culturing spleen cells with 10 U/ml of interleukin-2 for 4 days. In contrast, very little activity was generated under the same culture conditions when nonparenchymal liver cells were used as the responding cells. It was concluded that Kupffer cells produced prostaglandin and interferon alpha/beta, which suppressed lymphokine-activated-killer induction because (a) induction of lymphokine-activated-killer activity from nonparenchymal liver cells was observed in the presence of indomethacin and anti-interferon alpha/beta antibody; (b) when adherent nonparenchymal liver cells, primarily Kupffer cells, were removed, lymphokine-activated-killer activity could be obtained with interleukin-2 alone; (c) coculture of Kupffer cells with nonadherent nonparenchymal liver cells in a two-chambered system inhibited lymphokine-activated killer cell induction in a dose-dependent manner; (d) exogenous prostaglandin E2 and interferon alpha/beta added at the start of culture inhibited interleukin-2-induced cytotoxicity and proliferation, whereas the other major prostaglandin species in the liver, prostaglandin D2, had little effect. These findings are distinctive with Kupffer cells because splenic macrophages did not exert such inhibition in parallel experiments. Moreover, the supernatant collected from the 24-hr culture of nonparenchymal liver cells contained greater than 20-fold more prostaglandin E2 and interferon alpha/beta than that from culture of spleen cells. In subsequent in vivo experiments, when interleukin-2 was given intraperitoneally to mice, the combination of indomethacin and anti-interferon alpha/beta antibody significantly enhanced lymphokine-activated-killer activity recovered from the liver.(ABSTRACT TRUNCATED AT 250 WORDS) .A Tzung SP; Gaines KC; Lance P; Ehrke MJ; Cohen SA. .I 275201 .U 91007676 .S Hepatology 9101; 12(4 Pt 1):653-6 .M Acute Disease; Disease Outbreaks/*; DNA, Viral/*BL; Female; Fertilization in Vitro; Gene Amplification; Hepatitis B/BL/*MI/TM; Hepatitis B e Antigens/BL; Hepatitis B Surface Antigens/BL; Hepatitis B Virus/*GE; Human; Polymerase Chain Reaction; Specimen Handling. .T HBV-DNA detection by gene amplification in acute hepatitis B. .P JOURNAL ARTICLE. .W Serum samples from 62 women, inadvertently infected with hepatitis B virus in an in vitro fertilization program, were tested for the presence of hepatitis B virus-DNA using the polymerase chain reaction. Under conditions of a strict spatial separation of DNA extraction, amplification and product analysis, we succeeded in detection of as few as 360 hepatitis B virus particles per milliliter. Hepatitis B virus-DNA was detected with a high frequency during HBsAg and HBeAg antigenemia (98.5%) but also in the convalescent phase after appearance of antibody to HBsAg (18.2%). However, all patients with hepatitis B virus-DNA in convalescent sera were hepatitis B virus-DNA negative 3 to 6 mo later. All patients with HBeAg-positive samples showed hepatitis B virus-DNA positivity by polymerase chain reaction. For acute hepatitis, gene amplification restores the relationship between HBeAg and hepatitis B virus-DNA observed in serum from chronic hepatitis B patients and calls attention to the prolonged presence of hepatitis B virus-DNA in serum after generally accepted criteria for resolution of the infection have been reached. .A Quint WG; de Bruijn I; Kruining H; Heijtink RA. .I 275202 .U 91007677 .S Hepatology 9101; 12(4 Pt 1):657-60 .M Alanine Aminotransferase/*BL; Child; Chronic Disease; DNA, Viral/*BL; Female; Follow-Up Studies; Hepatitis B/*BL/EN/MI; Hepatitis B e Antigens/*BL; Hepatitis B Virus/*GE/IM; Human; Male; Time Factors. .T Changes of serum hepatitis B virus DNA and aminotransferase levels during the course of chronic hepatitis B virus infection in children. .P JOURNAL ARTICLE. .W During a follow-up period of 3.2 +/- 1.6 (1 to 8.6) yr, 1,087 serum specimens from 230 HBsAg carrier children were tested for hepatitis B virus markers. Dividing the serum specimens into four groups according to the status of HBeAg and hepatitis B virus DNA, the frequency of abnormally elevated ALT levels in serum was in the following order: HBeAg(+)/hepatitis B virus DNA(-) serum (60%), HBeAg(-)/hepatitis B virus DNA(+) serum (53%), HBeAg(+)/hepatitis B virus DNA(+) serum (41%), HBeAg(-)/hepatitis B virus DNA(-) serum (11%). Analysis of the data before HBeAg clearance showed that both a high serum ALT level and a low serum hepatitis B virus DNA level correlated with an imminent clearance of HBeAg. Approximately two thirds of children with serum ALT levels higher than 100 IU/L cleared HBeAg within the following year. Clearance of HBeAg occurred within the following year in 65% (13 of 20) of cases with serum hepatitis B virus DNA level less than or equal to 1,000 pg/ml, in contrast to 19% (30 of 157) of those with serum hepatitis B virus DNA level greater than 1,000 pg/ml. Among 53 children who lost HBeAg and hepatitis B virus DNA during follow-up, only nine cases did not have an identified period of abnormal serum ALT levels. For the remaining 44 children, abnormal serum ALT levels fell to normal with clearance of both HBeAg and hepatitis B virus DNA in 33 children but remained elevated in the remaining 11 cases after seroconversion.(ABSTRACT TRUNCATED AT 250 WORDS) .A Lee PI; Chang MH; Lee CY; Hsu HY; Chen JS; Chen PJ; Chen DS. .I 275203 .U 91007679 .S Hepatology 9101; 12(4 Pt 1):664-70 .M Antigens, Surface/*AN/IM; Autoantigens/*AN/IM; Autoimmune Diseases/*IM; Chromatography, Thin Layer; Enzyme-Linked Immunosorbent Assay; Glycosphingolipids/*IM; Hepatitis, Chronic Active/BL/*IM; Human; Liver/*IM; Membrane Lipids/*IM; Sulfatides/*AN/IM; Support, Non-U.S. Gov't. .T Hepatocyte plasma membrane glycosphingolipid reactive with sera from patients with autoimmune chronic active hepatitis: its identification as sulfatide. .P JOURNAL ARTICLE. .W Sera from patients with autoimmune chronic active hepatitis were found to contain IgG-class antibody to the acidic glycosphingolipid fraction from rabbit hepatocyte plasma membrane by solid-phase enzyme-linked immunosorbent assay. Using serum positive for the antibody as a probe, we isolated the target antigen by Iatrobeads column chromatography. Analysis by thin-layer chromatography and negative ion fast atom-bombardment mass spectrometry revealed that the antigen was sulfatide. The presence of antisulfatide antibody was also confirmed by immunoblotting. The reactivity of the serum with sulfatide was diminished by preincubation of the serum with galactosylceramide-6-sulfate and sulfatide, indicating that the antibody reacted with sulfated galactosylceramide regardless of the position of the sulfate residue. The antibody was found in 92.3%, 42.9%, 15.8%, 14.2%, 0% and 0%, respectively, of patients with autoimmune chronic active hepatitis, primary biliary cirrhosis, cirrhosis, systemic lupus erythematosus, chronic active hepatitis and chronic persistent hepatitis. Thus antisulfatide antibody was characteristic of autoimmune-type chronic liver diseases. Antisulfatide antibody was absorbed by rabbit hepatocyte plasma membrane. Preincubation of sera with sulfatide immobilized on Sepharose decreased their reactivities with not only sulfatide but also rabbit plasma membrane and rat hepatocytes. Therefore sulfatide may be a target antigen of the antibody to hepatocyte surface membrane. .A Toda G; Ikeda Y; Kashiwagi M; Iwamori M; Oka H. .I 275204 .U 91007681 .S Hepatology 9101; 12(4 Pt 1):676-9 .M Adult; Case Report; DNA, Viral/*AN; Female; Hepatitis B Surface Antigens/BL; Hepatitis B Virus/*GE/IM; Hepatoma/*CH/IM/PA; Human; Liver Neoplasms/*CH/IM/PA. .T HBV-DNA sequences in tumor and nontumor tissue in a patient with the fibrolamellar variant of hepatocellular carcinoma. .P JOURNAL ARTICLE. .W One patient with the fibrolamellar variant of hepatocellular carcinoma was found to be seropositive for HBsAg and anti-HBe. DNA from tumor and nontumor areas of the liver was examined by molecular hybridization for hepatitis B virus DNA sequences. Undigested DNA from the tumor gave a high-molecular-weight smear, and restriction-enzyme analysis indicated a single instance of integration. Nontumor liver tissue was analyzed from three separate areas. Hepatitis B virus DNA was detected in two of these; restriction-enzyme digestion suggested they contained different sites of viral integration. As with the typical hepatitis B virus-related hepatocellular carcinoma, analysis of hepatitis B virus DNA from nontumorous liver yielded a different pattern of high-molecular-weight bands, indicating that the virus genome had integrated at different chromosomal locations than that seen in the tumor. The finding of integrated hepatitis B virus DNA, especially in tumorous but also in nontumorous liver, would be consistent with an oncogenic role for hepatitis B virus in certain instances of fibrolamellar tumors and in the more typical hepatitis B virus-related hepatocellular carcinoma. .A Davison FD; Fagan EA; Portmann B; Williams R. .I 275205 .U 91007682 .S Hepatology 9101; 12(4 Pt 1):680-7 .M alpha Fetoproteins/*AN; Adult; Aged; Female; Hepatoma/BL/*DI/EP/US; Human; Liver Cirrhosis/BL/*CO; Liver Neoplasms/BL/*DI/EP/US; Male; Middle Age; Prospective Studies; Time Factors. .T Prospective study of early detection of hepatocellular carcinoma in patients with cirrhosis. .P JOURNAL ARTICLE. .W We prospectively monitored 140 cirrhotic patients for the development of hepatocellular carcinoma for 6 yr, using periodical screening by high-resolution convex-array ultrasonography and alpha-fetoprotein. Twenty-eight patients were positive for HBs antigen, 26 patients had received blood transfusions and were negative for HBs antigen and 26 patients had a history of heavy drinking. We detected hepatocellular carcinoma in 40 patients during this period. The overall cumulative incidence of hepatocellular carcinoma in the 6 yr was 39%; the cumulative incidence was 59% in patients with HBsAg, 53% in patients who had had blood transfusions and were negative for HBsAg and 22% in patients who had a history of heavy drinking and who were without HBsAg. Detection of the carcinoma in 85% of these 40 patients was based on results of ultrasonography. Twenty-six of the patients (65%) had a small hepatocellular carcinoma of 2 cm or less. alpha-Fetoprotein levels were lower than 100 ng/ml in 56% of these 40 patients. Patients with cirrhosis are at high risk of developing hepatocellular carcinoma, especially patients with HBsAg or with a history of blood transfusion who are negative for HBsAg. Periodic monitoring by use of ultrasonography in particular is recommended for early detection of hepatocellular carcinoma. .A Oka H; Kurioka N; Kim K; Kanno T; Kuroki T; Mizoguchi Y; Kobayashi K. .I 275206 .U 91007683 .S Hepatology 9101; 12(4 Pt 1):688-94 .M Chronic Disease; Evoked Potentials, Auditory/*; Hepatic Encephalopathy/*DI/PP/PX; Human; Liver Cirrhosis/PP/PX; Psychometrics. .T The auditory P300 event-related potential: an objective marker of the encephalopathy of chronic liver disease. .P JOURNAL ARTICLE. .W Recently many variants of electroencephalogram-evoked responses have been studied as potential diagnostic aids in the detection and evaluation of hepatic encephalopathy. This study assesses the value of the auditory P300 event-related potential--a slow component of the auditory evoked response--as a tool in this field. Twenty-one nonencephalopathic and 12 encephalopathic (grade 1/2) cirrhotic patients and 26 controls were assessed clinically and psychometrically. Electroencephalogram spectral analysis and visual evoked response recordings were also conducted. An auditory P300 wave was elicited using the standard two-tone discrimination paradigm. The latency and amplitude of this wave were measured. The latency of the P300 was found to be significantly increased in the encephalopathic patients compared with both nonencephalopathic cirrhotic and control groups (p less than 0.05). Amplitude of the wave was decreased in both nonencephalopathic and encephalopathic patients, but this was not statistically significant. This study suggests that the latency of the P300 is a good marker of grades 1 and 2 clinical hepatic encephalopathy. The delays in the P300 latency may indicate that encephalopathic patients have a deterioration of their stimulus evaluation abilities. .A Davies MG; Rowan MJ; MacMathuna P; Keeling PW; Weir DG; Feely J. .I 275207 .U 91007684 .S Hepatology 9101; 12(4 Pt 1):695-700 .M Amino Acids/BL; Animal; Brain Chemistry/*; Cerebral Cortex/CH; Dopamine/*AN; Hepatic Encephalopathy/CI/*ME; Hippocampus/CH; Hydroxyindoleacetic Acid/AN; Male; Methoxyhydroxyphenylglycol/AN; Norepinephrine/*AN; Rats; Rats, Inbred Strains; Serotonin/*AN; Support, Non-U.S. Gov't; Thioacetamide. .T Increased serotoninergic and noradrenergic activity in hepatic encephalopathy in rats with thioacetamide-induced acute liver failure. .P JOURNAL ARTICLE. .W Functional changes of various neurotransmitter systems have been implicated in the pathogenesis of hepatic encephalopathy. In this study the role of brain monoaminergic neurotransmitter systems in hepatic encephalopathy was investigated in rats with thioacetamide-induced acute liver failure. Concentrations of serotonin, dopamine, noradrenaline and of their metabolites 5-hydroxyindoleacetic acid, dihydroxyphenylalanine (following inhibition of dihydroxyphenylalanine-decarboxylase), dihydroxyphenylacetic acid, homovanillic acid and 3-methoxy-4-hydroxyphenyl-glycol, were measured in the cerebral cortex, striatum and hippocampus by high performance liquid chromatography with electrochemical detection. In hepatic encephalopathy concentrations of 5-hydroxyindoleacetic acid were increased in all three brain areas (196%, 204% and 264% of saline-treated controls, p less than 0.01), and concentrations of serotonin were increased in the frontal cortex (121%, p less than 0.01). In the frontal cortex and hippocampus of encephalopathic rats dopamine levels were increased (157% and 289%, p less than 0.05), and levels of noradrenaline (53% and 46%, p less than 0.05) were decreased associated with increased 3-methoxy-4-hydroxyphenylglycol levels (173% and 206%, p less than 0.05). The extent of these changes correlated with the stage of hepatic encephalopathy. In hepatic encephalopathy dihydroxyphenylalanine accumulation was increased in the hippocampus and unchanged in the cerebral cortex. Dopamine, noradrenaline, dihydroxyphenylacetic acid and homovanillic acid concentrations were unchanged in the striatum. The results of this study indicate that hepatic encephalopathy in thioacetamide-induced acute liver failure in rats is associated with neurochemical changes, suggesting an increased activity of the noradrenergic and serotoninergic neurotransmitter systems. .A Yurdaydin C; Hortnagl H; Steindl P; Zimmermann C; Pifl C; Singer EA; Roth E; Ferenci P. .I 275208 .U 91007685 .S Hepatology 9101; 12(4 Pt 1):701-9 .M Age Factors; Animal; Carbamyl Phosphate Synthase (Ammonia)/BI/*GE; Cell Communication/*; Gene Expression Regulation, Enzymologic/*; Glutamine Synthetase/BI/*GE; Liver/CY/*EN; Liver Transplantation; Phenotype; Rats; Rats, Inbred Strains; Spleen/*. .T Hepatocytes explanted in the spleen preferentially express carbamoylphosphate synthetase rather than glutamine synthetase. .P JOURNAL ARTICLE. .W Urea cycle enzymes and glutamine synthetase are essential for NH3 detoxification and systemic pH homeostasis in mammals. Carbamoylphosphate synthetase, the first and flux-determining enzyme of the cycle, is found only in a large periportal compartment, and glutamine synthetase is found only in a small, complementary pericentral compartment. Because it is not possible to manipulate experimentally the intrahepatic distribution of carbamoylphosphate synthetase and glutamine synthetase, we looked for conditions in which explanted hepatocytes would exhibit either the carbamoylphosphate synthetase phenotype or glutamine synthetase phenotype. In the spleen hepatocytes either settle as individual cells or in small agglomerates. The dispersed cells only express the carbamoylphosphate synthetase phenotype. Within the agglomerates, sinusoids that drain on venules develop. Hepatocytes surrounding the venules stain only weakly for carbamoylphosphate synthetase but are strongly positive for glutamine synthetase. These observations were made for explanted embryonic hepatocytes (no prior expression of either carbamoylphosphate synthetase or glutamine synthetase), neonatal hepatocytes (compartments of gene expression not yet established) and adult periportal and pericentral hepatocytes. .A Lamers WH; Been W; Charles R; Moorman AF. .I 275209 .U 91007686 .S Hepatology 9101; 12(4 Pt 1):710-5 .M Antibiotics/TU; Ascites/CO/IM/*MI/SU; Bacterial Infections/*; Cell Movement; Complement 5a/AN; Drainage; Human; Neutrophils/*; Peritonitis/CO/DT/*MI; Prospective Studies; Support, U.S. Gov't, P.H.S.. .T Monomicrobial nonneutrocytic bacterascites: a variant of spontaneous bacterial peritonitis. .P JOURNAL ARTICLE. .W Spontaneous bacterial peritonitis is diagnosed when (a) the ascitic fluid culture is positive, (b) the ascitic fluid neutrophil count is greater than or equal to 250 cells/mm3 and (c) there is no evident intraabdominal surgically treatable source for infection. Few details are available regarding the variant of ascitic fluid infection in which the culture grows bacteria (pure growth of a single type of organism), but the neutrophil count is less than 250 cells/mm3. In this prospective study of 138 episodes of culture-positive spontaneously infected ascites detected in 105 patients, 44 (31.9%) were episodes of "monomicrobial nonneutrocytic bacterascites" compared with 94 (68.1%) episodes of spontaneous bacterial peritonitis. Seventeen patients had both types of infection. The infection-related mortality and hospitalization mortality were similar between the two groups. Patients with bacterascites appeared to have less severe liver disease. In 62% of bacterascites episodes in which a second paracentesis was performed before any treatment the fluid spontaneously became sterile without development of ascitic fluid neutrocytosis. Thirty-eight percent of patients with bacterascites (who underwent a second paracentesis before treatment was started) progressed to spontaneous bacterial peritonitis--sometimes within a few hours. The concentration of the chemoattractant C5a was not decreased in the ascitic fluid of the bacterascites patients; this excludes ascitic fluid C5a deficiency as the explanation of the lack of neutrocytosis. Monomicrobial nonneutrocytic bacterascites is a common variant of ascitic fluid infection that may resolve without treatment or may progress to spontaneous bacterial peritonitis. .A Runyon BA. .I 275210 .U 91007687 .S Hepatology 9101; 12(4 Pt 1):716-24 .M Bacterial Infections/MO/*PC; Double-Blind Method; Drug Administration Schedule; Feces/MI; Female; Human; Liver Cirrhosis/*CO; Male; Middle Age; Norfloxacin/AD/*TU; Patient Compliance; Peritonitis/MO/*PC; Recurrence; Support, Non-U.S. Gov't. .T Norfloxacin prevents spontaneous bacterial peritonitis recurrence in cirrhosis: results of a double-blind, placebo-controlled trial. .P CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY. .W Eighty cirrhotic patients who had recovered from an episode of spontaneous bacterial peritonitis were included in a multicenter, double-blind trial aimed at comparing long-term norfloxacin administration (400 mg/day; 40 patients) vs. placebo (40 patients) in the prevention of spontaneous bacterial peritonitis recurrence. At entry, both groups were similar with respect to clinical and laboratory data, ascitic fluid protein and polymorphonuclear concentrations, number of previous episodes of spontaneous bacterial peritonitis and causative organisms of the index spontaneous bacterial peritonitis. Norfloxacin administration produced a selective intestinal decontamination (elimination of aerobic gram-negative bacilli from the fecal flora without significant changes in other microorganisms) throughout the study in six patients in whom the effect of norfloxacin on the fecal flora was periodically assessed. Fourteen patients from the placebo group (35%) and five from the norfloxacin group (12%) developed spontaneous bacterial peritonitis recurrence during follow-up (chi 2 = 5.97; p = 0.014) (mean follow-up period = 6.4 +/- 0.6 mo; range = 1 to 19 mo). Ten of the 14 spontaneous bacterial peritonitis recurrences in the placebo group and only one of the five spontaneous bacterial peritonitis recurrences in the norfloxacin group were caused by aerobic gram-negative bacilli (chi 2 = 8.87; p = 0.0029). The overall probability of spontaneous bacterial peritonitis recurrence at 1 yr of follow-up was 20% in the norfloxacin group and 68% in the placebo group (p = 0.0063) and the probability of spontaneous bacterial peritonitis recurrence caused by aerobic gram-negative bacilli at 1 yr of follow-up was 3% and 60%, respectively (p = 0.0013).(ABSTRACT TRUNCATED AT 250 WORDS) .A Gines P; Rimola A; Planas R; Vargas V; Marco F; Almela M; Forne M; Miranda ML; Llach J; Salmeron JM; et al. .I 275211 .U 91007688 .S Hepatology 9101; 12(4 Pt 1):725-8 .M Collateral Circulation/*; Human; Hypertension, Portal/*PP/RA; Nomenclature; Stomach/*BS; Veins/AH. .T Relative frequencies of portosystemic pathways and renal shunt formation through the "posterior" gastric vein: portographic study in 460 patients. .P JOURNAL ARTICLE. .W Percutaneous transhepatic portography was carried out in 460 patients with portal hypertension to study various collateral routes. Besides the left gastric vein, which was the most frequent collateral route and feeder of esophageal varices, a distinct vein located between the left gastric vein and the short gastric vein constituted a major collateral route in 191 patients (42%). In terms of frequency, this vein was more significant than the short gastric (34%) and the paraumbilical vein (24%) as a collateral route. We propose that this previously anonymous vein be called the "posterior gastric" vein because it runs posterior to the stomach. This vein also formed a renal shunt, a common cause of encephalopathy, in 43 (23%) of the 191 patients; the relative frequency of renal shunt formation by this vein was significantly greater than that by the left gastric vein (12%) and the short gastric vein (18%). .A Kimura K; Ohto M; Matsutani S; Furuse J; Hoshino K; Okuda K. .I 275212 .U 91007689 .S Hepatology 9101; 12(4 Pt 1):729-37 .M Absorption; Albumins/*PK; Animal; Chlorides/ME; Cholelithiasis/CH; Cholesterol/ME; Comparative Study; Gallbladder/*ME; Human; Perfusion; Proteins/*SE; Sodium/ME; Support, Non-U.S. Gov't; Swine; Water/ME. .T Albumin absorption and protein secretion by the gallbladder in man and in the pig. .P JOURNAL ARTICLE. .W To study albumin absorption by the gallbladder in man, an in vitro model was first established in the pig and compared with in vivo function in the same species. Water and electrolyte transport and 125I-albumin absorption and protein secretion in vivo and in vitro were compared. Then similar in vitro studies were performed on human gallbladders obtained at surgery. The in vivo study in the pig was performed without disturbing the gallbladder except to tie a cannula in the cystic duct end. The in vitro model was identical in the pig and human gallbladders. Gallbladders were excised using a technique causing minimal injury and anoxia. They were oxygenated on both mucosal and serosal surfaces in a temperature-controlled environment. Luminal and external bath test solutions consisted of modified Ringers bicarbonate with added glucose; luminal solutions also contained 125I-albumin from different species, depending on the study. Active absorption of sodium and water occurred in both types of studies in the pig but in vivo absorption rates were considerably greater than in vitro rates. Albumin absorption in vivo was substantial; although present in vitro, the absorption of albumin was diminished relatively more than electrolyte transport rates. Protein secretion rates into the gallbladder were similar in vitro and in vivo. The results of studies in the human gallbladders in vitro were similar to the pig, except albumin absorption was greater. Some human gallbladders were obtained from control patients and some from patients with cholesterol gallstones. There were no significant differences between the two groups for any of the variables studied; however, the numbers were small and some control gallbladders were not normal gallbladders. .A Toth JL; Harvey PR; Upadyha GA; Strasberg SM. .I 275213 .U 91007690 .S Hepatology 9101; 12(4 Pt 1):738-42 .M Animal; Bile/SE; Biological Transport; Chenodeoxycholic Acid/*ME; Liver/*ME/SE; Male; Perfusion; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Transport of chenodeoxycholic acid and its 3-alpha- and 7-alpha-sulfates by isolated perfused rat liver. .P JOURNAL ARTICLE. .W In patients with cholestasis, levels of sulfated bile acids rise. Sulfate esters of chenodeoxycholic acid are the most abundant of these bile acid sulfates. These compounds are taken up by the liver and excreted into bile, although their plasma clearance and biliary excretion are reduced compared with that of unsulfated bile acids. It is not clear whether this is due to differences in intrinsic hepatic uptake or biliary excretion. In the present study, single-pass transport kinetics of chenodeoxycholic acid 3-alpha-sulfate, chenodeoxycholic acid 7-alpha-sulfate and unsulfated chenodeoxycholic acid were quantified in isolated perfused rat liver. Influx of the 7-alpha- and 3-alpha-sulfated derivatives was 57% and 20% that of chenodeoxycholic acid, respectively. These three compounds bound to albumin equally well, indicating that this was not a factor in their differential uptake. Although single-pass extraction of material taken up by the liver was identical. There was no difference in bile flow or biliary excretion of material taken up by the liver was identical. There was no difference in bile flow or biliary excretion rate, regardless of which bile acid sulfate was tested. These results indicate that the low plasma elimination of sulfated bile acids previously observed by others can be explained by low hepatic influx. The diminished transport into liver resulting from sulfation could lead to enhanced elimination of bile acids by the kidney. .A Gartner U; Goeser T; Stiehl A; Raedsch R; Wolkoff AW. .I 275214 .U 91007691 .S Hepatology 9101; 12(4 Pt 1):743-6 .M Amyloid/*ME; Amyloidosis/*ME/PA; Bile Ducts, Intrahepatic/*ME/PA; Human. .T Amyloid deposition in intrahepatic large bile ducts and peribiliary glands in systemic amyloidosis. .P JOURNAL ARTICLE. .W Amyloid deposition in the hepatic parenchyma and portal tracts in the liver is well known in systemic amyloidosis. We recently experienced an autopsy case of systemic amyloidosis presenting the amyloid deposits in the intrahepatic biliary tree. This experience prompted us to survey 19 autopsy cases of systemic amyloidosis. Amyloid deposition was found just under the lining epithelium of the intrahepatic large bile duct in 10 of 19 cases and around the peribiliary glandular acini in 7 of the 19 cases, respectively. Amyloid deposition in the intrahepatic large bile duct and peribiliary glands was positively correlated with the degree of amyloid deposition in the liver but not with type of amyloid protein. Double-staining of amyloid and vascular endothelium disclosed that amyloid deposition was more closely related to the inner part of the peribiliary vascular plexus and to the vascular plexus encircling the peribiliary glands than the lining biliary epithelium and peribiliary glandular acinar cells themselves. The exact pathogenesis of amyloid deposition in these anatomical components, however, remains unclear. Although our cases failed to show any overt clinical symptomatologies related to amyloid deposition in these biliary components, it seems conceivable that more massive amyloid deposition in these anatomical components could give rise to some clinical symptoms. .A Sasaki M; Nakanuma Y; Terada T; Hoso M; Saito K; Hayashi M; Kurumaya H. .I 275215 .U 91007692 .S Hepatology 9101; 12(4 Pt 1):747-52 .M Adult; Aged; Bile Duct Diseases/*PA; Bile Duct Neoplasms/*PA; Biopsy/IS/MT; Constriction, Pathologic/PA; Evaluation Studies; Female; Human; Male; Middle Age; Odds Ratio. .T Diagnostic value of brush cytology in the diagnosis of bile duct carcinoma: a study in 65 patients with bile duct strictures. .P JOURNAL ARTICLE. .W Malignant strictures of the extrahepatic bile ducts are difficult to distinguish from benign strictures, particularly in patients with primary sclerosing cholangitis. Because attempts at diagnosing small cancers with fine-needle aspiration biopsy are not possible in the absence of an associated mass lesion and because the sensitivity of exfoliative biliary cytology is controversial, brush cytology has been used as a potential means of establishing a specific diagnosis of bile duct carcinoma. Herein we report our experience with this technique when performed on 65 patients over a 5-yr period. Each had at least one brushing. Thirty-seven were found to have bile duct carcinoma and 28 were found to have benign strictures. Of these 37, the first brushing was positive for malignancy in 15 (40%), whereas four (11%) had cells suspected but not diagnostic of malignancy. Thirteen patients with bile duct carcinoma whose initial brushings were negative for malignancy had second brushings. Of these, five (38%) had malignant cells, whereas three (24%) yielded suspicious cells. Three of the eight whose first two brushings were negative for malignancy were found to have malignant cells on the third brushing. In contrast, of the 28 patients with benign strictures, malignant cells were never found. However, in two patients, suspicious cells were reported with the first but not the second brushing. A single negative or suspicious cytological finding decreased the probability of bile duct carcinoma to 43%. Two and three sequential negative tests reduced the probability to 32% and 0%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) .A Rabinovitz M; Zajko AB; Hassanein T; Shetty B; Bron KM; Schade RR; Gavaler JS; Block G; Van Thiel DH; Dekker A. .I 275216 .U 91007693 .S Hepatology 9101; 12(4 Pt 1):753-60 .M Adult; Female; Follow-Up Studies; Hepatoma/BL/*MO/TH; Human; Liver Neoplasms/BL/*MO/TH; Male; Models, Biological; Multivariate Analysis; Prognosis; Regression Analysis; Support, Non-U.S. Gov't. .T Prognostic factors of hepatocellular carcinoma in the west: a multivariate analysis in 206 patients. .P JOURNAL ARTICLE. .W To investigate the prognostic factors in Western patients with hepatocellular carcinoma, 206 patients with confirmed diagnoses of hepatocellular carcinoma were studied in terms of survival. All patients were diagnosed between 1983 and 1987. A multivariate survival analysis (Cox regression model) using clinical, biochemical, ultrasonographical and pathological data obtained at diagnosis disclosed that bilirubin (p = 0.0001), ascites (p = 0.0001), toxic syndrome (defined by the presence of weight loss greater than 10% premorbid weight, malaise and anorexia) (p = 0.009), blood urea nitrogen (p = 0.025), tumor size (p = 0.001), gamma-glutamyltranspeptidase (p = 0.0006), age (p = 0.0005), serum sodium (p = 0.003) and presence of metastases (p = 0.002) were independent predictors of survival. According to the contribution of each of these factors to the final model, a prognostic index was constructed allowing division of patients in different groups according to their relative risk of death: RRD = EXP (Age x 0.03 + Ascites x 0.8281 + BUN x 0.0137 + Serum sodium x (-0.0538) + gamma-Glutamyltranspeptidase x 0.0019 + Bilirubin x 0.0734 + Tumor size x 0.33 + Toxic syndrome x 0.4965 + Metastases x 0.55). These results facilitate the stratification of hepatocellular carcinoma patients to design and evaluate future controlled trials. .A Calvet X; Bruix J; Gines P; Bru C; Sole M; Vilana R; Rodes J. .I 275217 .U 91007694 .S Hepatology 9101; 12(4 Pt 1):761-75 .M Bile Duct Neoplasms/DI; Carcinoma/DI; Comparative Study; Cysts/DI; Diagnosis, Differential; Hemangioma/DI; Human; Liver Abscess/DI; Liver Neoplasms/*DI/RA/RI/SC/US; Magnetic Resonance Imaging; Tomography, X-Ray Computed. .T Review of hepatic imaging and a problem-oriented approach to liver masses. .P JOURNAL ARTICLE; REVIEW; REVIEW, MULTICASE. .W We believe that imaging of the liver is complicated. The sporadic appearance of incidental benign lesions and variability in scanning techniques, equipment and artifacts add difficulties to the evaluation of liver masses. Therefore we emphasize the need to define the problem for which the patient is being imaged. This information helps in choosing the procedure of choice and the technique needed to give the most expedient, accurate answer. This will also help apply the lowest risk and most cost-efficient care. Imaging algorithms vary depending on the suspected pathological conditions. Dynamic bolus-enhanced CT is the modality of choice in most situations. Tc99m sulfur-colloid liver-spleen scans are helpful in patients with suspected FNH, and Tc99m-tagged-RBC-SPECT scans are recommended to confirm cavernous hemangiomas. Cysts are easily confirmed by US. Although MRI is competitive with CT, it has not become a primary modality because of cost, availability, patient selection and variability of scanner capabilities among the many manufacturers and models. It is hard to predict what future development of imaging techniques will bring. Many feel that significant advances have plateaued. Time and money will more likely be concentrated on improving image resolution, speed of scanning and ability to transfer this information to sites outside of the radiology department. In addition to faster scanning, we expect to soon have available safe intravenous and enteric contrast agents for MRI. Certainly this will lead to a new round of investigations to compare MRI with CT scanning. .A Bennett WF; Bova JG. .I 275218 .U 91007695 .S Hepatology 9101; 12(4 Pt 1):776-81 .M Antibiotics/TU; Bacterial Infections/*; Human; Liver Cirrhosis/*CO; Norfloxacin/TU; Peritonitis/*ET/PC/TH. .T Spontaneous bacterial peritonitis: prevention and therapy [editorial] .P EDITORIAL. .A Hoefs JC. .I 275219 .U 91007696 .S Hepatology 9101; 12(4 Pt 1):782-3 .M Giant Cell Tumors/*PA; Hepatoma/*PA; Human; Liver Neoplasms/*PA; Osteoclasts/PA. .T Liver cell carcinoma with osteoclast-like giant cells: nonepitheliogenic giant cells in diverse malignancies. .P JOURNAL ARTICLE. .A Rosai J. .I 275220 .U 91007697 .S Hepatology 9101; 12(4 Pt 1):783-4 .M Esophageal and Gastric Varices/*TH; Esophagoscopy/*; Gastrointestinal Hemorrhage/*TH; Human; Ligation. .T Endoscopic ligation of esophageal varices: an endoscopist's opinion. .P JOURNAL ARTICLE. .A Tedesco FJ. .I 275221 .U 91007698 .S Hepatology 9101; 12(4 Pt 1):784-6 .M Arthritis, Rheumatoid/CO/*DT; Biopsy; Human; Liver/*DE/PA; Liver Cirrhosis/CI/CO; Methotrexate/*AE. .T Methotrexate hepatotoxicity and the premature reporting of Mark Twain's death: both greatly exaggerated. .P JOURNAL ARTICLE. .A Kaplan MM. .I 275222 .U 91007699 .S Hepatology 9101; 12(4 Pt 1):786-7 .M Ascites/PP; Blood Pressure/*; Cardiac Output; Heart Rate; Human; Liver Cirrhosis/*PP/TH; Oxygen Consumption; Oxygen Inhalation Therapy/*; Pressoreceptors/PP. .T Effects of oxygen inhalation in ascitic cirrhotic patients: therapeutic implications? .P JOURNAL ARTICLE. .A Henriksen JH. .I 275223 .U 91007700 .S Hepatology 9101; 12(4 Pt 1):790-1 .M Alanine Aminotransferase/*BL; Chronic Disease; Female; Hepatitis B/*EN; Hepatitis B Virus/*PH; Human; Interferon Alfa, Recombinant/*TU; Male; Virus Replication. .T Interferon treatment and ALT normalization concomitant with ongoing viral replication [letter; comment] .P COMMENT; LETTER. .A Taliani G; Clementi C; Lecce R; Grimaldi F; De Bac C. .I 275224 .U 91007701 .S Hepatology 9101; 12(4 Pt 2):838-1046 .M Animal; Digestive System Diseases/*; Human; Liver Diseases/*. .T The American Association for the Study of Liver Diseases. Postgraduate course & 41st annual meeting. November 3-6, 1990, Chicago, Illinois. Abstracts. .P MEETING REPORT; OVERALL. .I 275225 .U 91007867 .S Hypertension 9101; 16(4):363-70 .M Angiotensin-Converting Enzyme Inhibitors/PD; Animal; Base Sequence; Human; Kininase II/CH/*PH; Molecular Sequence Data; Support, U.S. Gov't, P.H.S.. .T Angiotensin I converting enzyme and the changes in our concepts through the years. Lewis K. Dahl memorial lecture. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Changes in our concepts of angiotensin I converting enzyme are reviewed briefly. The actions of this enzyme go beyond liberating angiotensin II from angiotensin I or inactivating bradykinin. Its very wide distribution in the body and its activity in vitro indicate involvement in the metabolism of other biologically active peptides. The recent molecular cloning of the human enzyme confirmed the existence of a hydrophobic C-terminal peptide that forms the short transmembrane domain of this plasma membrane-bound enzyme. The much longer external portion contains two homologous active site domains but probably only one functional active center. Finally, in spite of the great progress made in studying angiotensin converting enzyme, there are many challenging problems waiting to be solved. .A Erdos EG. .I 275226 .U 91007868 .S Hypertension 9101; 16(4):371-86 .M Animal; Atherosclerosis/PP; Endothelium-Derived Relaxing Factor/AN/*PH; Human; Hydroxides; Hypertension/PP; Microcirculation/PH; Reperfusion Injury/PP; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Vasodilation. .T Endothelium-derived relaxing factors. A perspective from in vivo data. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W We review below published studies of endothelium-dependent vasodilation in vivo. Endothelium-dependent vasodilation has been demonstrated in conduit arteries in vivo and in the cerebral, coronary, mesenteric, and femoral vascular beds as well as in the microcirculation of the brain and the microcirculation of cremaster muscle. The available evidence, although not complete, strongly suggests that the endothelium-derived relaxing factor generated by acetylcholine in the cerebral microcirculation is a nitrosothiol. The endothelium-derived relaxing factor generated by bradykinin in this vascular bed is an oxygen radical generated in association with enhanced arachidonate metabolism via cyclooxygenase. In the microcirculation of skeletal muscle, on the other hand, the vasodilation from bradykinin is mediated partly by prostacyclin and partly by an endothelium-derived relaxing factor similar to that generated by acetylcholine. Basal secretion of endothelium-derived relaxing factor is controversial in vivo but is usually present in vitro. On the other hand, it appears that endothelium-derived relaxing factor mediates flow-dependent vasodilation in both large vessels and in the microcirculation in vivo. The generation and release of endothelium-derived relaxing factor from endothelium may be abnormal in a variety of conditions including acute and chronic hypertension, atherosclerosis, and ischemia followed by reperfusion. Several mechanisms for these abnormalities have been identified. These include inability to generate endothelium-derived relaxing factor or destruction of endothelium-derived relaxing factor by oxidants after its release in the extracellular space. These abnormalities in endothelium-dependent relaxation may contribute to the vascular abnormalities in these conditions. .A Marshall JJ; Kontos HA. .I 275227 .U 91007869 .S Hypertension 9101; 16(4):387-97 .M Aged; Aged, 80 and over; Echocardiography, Doppler; Female; Hemodynamics/*DE; Human; Hypertension/*PP; Male; Sodium/*PD; Time Factors; Ultrasonography; Vascular Resistance/DE. .T Time course of hemodynamic responses to sodium in elderly hypertensive patients. .P JOURNAL ARTICLE. .W Thirty-one patients with essential hypertension (81.6 +/- 6.9 years old) were studied during two different regimens of sodium intake: 120 meq/day for 8 weeks and 344 meq/day for 2 weeks. Systemic hemodynamic data were measured with Doppler echocardiography from which the mitral flow velocity integral, cardiac index, and total peripheral resistance were calculated. The salt-sensitive patients in whom the increase in total peripheral resistance was greater than the increase in cardiac index with salt loading were termed SST. In the salt-sensitive patients termed SSC, the increase in cardiac index was greater than the increase in total peripheral resistance with increased sodium intake. All SST patients on day 7 of the high sodium diet remained in the SST group on day 14. Nine of 13 patients in the SSC group on day 7 remained in the SSC group on day 14, and the remaining four patients in the SSC group on day 7 fell into the SST group on day 14. Four of eight non-salt-sensitive (NSS) patients on day 7 of the high salt regimen remained in the NSS group on day 14, whereas the remaining four patients in the NSS group on day 7 fell into the SSC group on day 14. Our data suggest a changing pattern with sodium loading of initially high cardiac index followed by a persistently raised total peripheral resistance. The celiac, superior mesenteric, and renal arteries vasoconstricted with sodium repletion in both SST and SSC patients. With salt loading, the terminal aortic vascular bed vasodilated in the SSC patients and vasoconstricted in the SST patients. .A Shimamoto H; Shimamoto Y. .I 275228 .U 91007870 .S Hypertension 9101; 16(4):398-406 .M Adult; Aged; Alcohol Drinking/*; Analysis of Variance; Apolipoproteins/BL; Blood Pressure; Diet, Sodium-Restricted/*; Human; Hypertension/*TH; Lipoproteins, HDL Cholesterol/BL; Male; Middle Age; Support, Non-U.S. Gov't. .T Two-way factorial study of alcohol and salt restriction in treated hypertensive men. .P JOURNAL ARTICLE. .W The aim of this study was to determine whether moderate restriction of dietary salt intake leads to an additional fall in blood pressure in treated hypertensive men who are asked to simultaneously reduce their usual alcohol intake. Sixty-three subjects entered an initial 2-week familiarization period during which they continued their usual alcohol intake and commenced a "low sodium" diet (less than 60 mmol/day) supplemented with 100 mmol sodium chloride per day as enteric-coated tablets. Subjects were then randomly assigned to either drink a low alcohol beer alone for a 4-week period (reducing their self-reported alcohol consumption from 537 to 57 ml/week) or to continue their usual alcohol intake (543 versus 557 ml/week). Within the low and normal alcohol intake groups, subjects were assigned to either a low or normal sodium intake. The low sodium groups continued the sodium-restricted diet but were switched to placebo sodium chloride tablets for the 4 weeks. This resulted in a fall in the 24-hour urinary sodium excretion from 144 to 69 mmol/day. The normal sodium groups continued the low sodium diet but kept taking 100 mmol/day of the sodium chloride tablets, and their urinary sodium excretion remained unchanged (125 versus 142 mmol/day). Regular antihypertensive therapy was continued throughout. Fifty-nine subjects completed the trial. In those who reduced their alcohol intake there was a fall in both systolic blood pressure (-5.4 mm Hg supine, p less than 0.01) and diastolic blood pressure (-3.2 mm Hg supine, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) .A Parker M; Puddey IB; Beilin LJ; Vandongen R. .I 275229 .U 91007871 .S Hypertension 9101; 16(4):407-13 .M Acid-Base Equilibrium/*; Adult; Blood Pressure/*DE; Human; Male; Sodium Chloride/*PD; Support, Non-U.S. Gov't. .T Salt sensitivity in humans is associated with abnormal acid-base regulation. .P JOURNAL ARTICLE. .W Metabolic acidosis has recently been observed in rat models of salt-sensitive genetic hypertension. To test the hypothesis that salt sensitivity in humans may be associated with abnormal acid-base homeostasis, we performed arterial blood gas analyses in young (20-31 years old) normotensive subjects (n = 40) who were placed on a low salt diet (20 mmol NaCl/day) for 2 weeks with either 200 mmol sodium chloride or placebo added to the low salt diet for 1 week each in a randomized, single-blind crossover order. Furthermore, a subset of the subjects (seven salt-sensitive and eight salt-resistant) received 200 mmol sodium/day as the citrate salt as a supplement to the low salt diet for a third week. During each regimen, blood pressure as well as arterial pH and bicarbonate levels were measured. Salt sensitivity was defined as a significant drop in mean arterial pressure greater than 3 mm Hg (mean of 30 readings taken during each diet, p less than 0.05) while the subject was on the low salt diet. According to this definition, 16 subjects were salt-sensitive and 24 salt-resistant. During the high sodium chloride regimen, arterial pH and bicarbonate levels were significantly lower in the salt-sensitive than in the salt-resistant group (p less than 0.0001). The increase in blood pressure caused by sodium chloride correlated inversely to the arterial pH (r = -0.57, p = 0.0002) and bicarbonate levels (r = -0.52, p = 0.0007) during the high salt diet. Sodium chloride increased mean arterial blood pressure in the salt-sensitive subjects; sodium citrate did not. Sodium citrate led to an increase in pH and bicarbonate levels in both groups. Our finding that a sodium chloride-induced rise in blood pressure is associated with lower arterial plasma pH and bicarbonate levels points to an abnormality in renal acid-base regulation in salt-sensitive subjects. .A Sharma AM; Kribben A; Schattenfroh S; Cetto C; Distler A. .I 275230 .U 91007872 .S Hypertension 9101; 16(4):414-21 .M Adult; Aged; Blood Pressure/*; Human; Middle Age; Pulse/*; Time Factors. .T Sequential spectral analysis of 24-hour blood pressure and pulse interval in humans. .P JOURNAL ARTICLE. .W Blood pressure and pulse interval are characterized not only by erratic variations but also by rhythmic fluctuations at low-, mid-, and high-frequency (0.025-0.07, 0.07-0.14, and 0.14-0.35 Hz, respectively). However, information on these phenomena has largely been derived from analysis of short-term recordings taken in standardized laboratory conditions. In seven normotensive and 10 untreated mild essential hypertensive subjects, power spectrum analysis was performed on the intra-arterial blood pressure and pulse interval signal collected over a 24-hour period using the fast Fourier transform algorithm and splitting the recording into contiguous segments of 256 beats. About 70% of the segments were suitable for the analysis; the segments excluded for a nonstationary signal amounted to only 30%. All powers were characterized by a high segment-to-segment variability, but in each subject the mid- and high-frequency powers of diastolic blood pressure and the mid-frequency power of systolic blood pressure were markedly reduced during the night as compared with the daytime period, whereas the opposite occurred for the low- and high-frequency powers of the pulse interval. Over the 24-hour period, mid- and high-frequency powers of blood pressure were positively correlated to each other, but both accounted for less than 25% of the 24-hour blood pressure variance. No difference between mean normalized power values of normotensive and hypertensive subjects was observed.(ABSTRACT TRUNCATED AT 250 WORDS) .A Parati G; Castiglioni P; Di Rienzo M; Omboni S; Pedotti A; Mancia G. .I 275231 .U 91007873 .S Hypertension 9101; 16(4):422-8 .M Animal; Blood Pressure/*; Circadian Rhythm/*; Heart Rate/*; Hypertension/*PP; Light; Motor Activity; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Support, U.S. Gov't, P.H.S.. .T Diurnal cardiovascular patterns in spontaneously hypertensive and Wistar-Kyoto rats. .P JOURNAL ARTICLE. .W This study was designed to determine whether diurnal patterns of blood pressure, heart rate, or locomotor activity differed among two substrains of Wistar-Kyoto rats, derived originally from Charles River or Taconic Farms stock, or the spontaneously hypertensive rat. Cardiovascular parameters were continuously monitored over 24 hours. Resting systolic and diastolic blood pressure values were statistically different among the three groups both during the lights-on (rest) and lights-off (active) phases of the cycle with blood pressure of spontaneously hypertensive rats greater than that of Wistar-Kyoto rats from Taconic Farms, which was greater than that of Wistar-Kyoto rats from Charles River. The largest difference in arterial pressure between Wistar-Kyoto/Taconic Farms and Wistar-Kyoto/Charles River was during the lights-on period. Heart rates of all rats decreased during the lights-on period; Wistar-Kyoto/Charles River had the largest decrease (-70 +/- 5 beats/min), Wistar-Kyoto/Taconic Farms had the least (-17 +/- 2 beats/min), and in spontaneously hypertensive rats the decrease was intermediate (-29 +/- 3 beats/min). The pronounced diurnal variation in pressure and heart rate exhibited by Wistar-Kyoto/Charles River was not present in either Wistar-Kyoto/Taconic Farms or spontaneously hypertensive rats. Blood pressure magnitude correlated with locomotor activity during both periods, although all groups showed minimal activity during the rest period. Observed differences between Wistar-Kyoto/Charles River and Wistar-Kyoto/Taconic Farms were not due to a lack of or an abnormality in baroreceptor reflex function.(ABSTRACT TRUNCATED AT 250 WORDS) .A Henry R; Casto R; Printz MP. .I 275232 .U 91007874 .S Hypertension 9101; 16(4):429-35 .M Angiotensin II/BL; Angiotensin-Converting Enzyme Inhibitors/*PD; Animal; Bicyclo Compounds/*PD; Blood Pressure/*DE; Bradykinin/PD; Kinins/DF/*PH; Male; Rats; Rats, Inbred BN; Species Specificity. .T Converting enzyme inhibition in kinin-deficient brown Norway rats. .P JOURNAL ARTICLE. .W The contribution of endogenous kinins to the acute antihypertensive actions of the converting enzyme inhibitor ramipril was investigated in kinin-deficient Brown Norway rats and in Brown Norway-Hannover rats and Wistar rats as controls. In Brown Norway rats, urinary kinin excretion was measurable but extremely low when compared with control strains. The depressor responses to intra-arterial bradykinin injections 1) were not different between Brown Norway and Brown Norway-Hannover rats, 2) were potentiated by intravenous ramipril (60 micrograms), and 3) were attenuated by intra-arterial infusion of the bradykinin antagonist B4146 (40 micrograms/kg/min) to a similar extent in both strains. In renal hypertensive (two-kidney, one clip) Brown Norway rats, the blood pressure reductions to intravenous bolus injections of ramipril (100 micrograms) were significantly reduced both in extent and duration when compared with hypertensive Brown Norway-Hannover and Wistar rats. Intra-arterial infusion of B4146 (40 micrograms/kg/min) attenuated the depressor response to ramipril in Wistar and Brown Norway-Hannover rats but had no effect in Brown Norway rats. In contrast, all three groups showed similar depressor responses to intravenous infusions of the angiotensin II receptor antagonist saralasin. These responses were not influenced by the bradykinin antagonist. Our data support the hypothesis that kinins are important for the acute antihypertensive actions of converting enzyme inhibitors. .A Danckwardt L; Shimizu I; Bonner G; Rettig R; Unger T. .I 275233 .U 91007875 .S Hypertension 9101; 16(4):436-40 .M Animal; Blood Vessels/*EN; Hypertension, Renovascular/*EN; Kallikrein/*AN; Lactate Dehydrogenase/AN; Male; Rats; Rats, Inbred Strains; Support, U.S. Gov't, P.H.S.. .T A kallikrein-like enzyme in blood vessels of one-kidney, one clip hypertensive rats. .P JOURNAL ARTICLE. .W Active and inactive kallikrein or a kallikrein-like enzyme are found in the aorta, vena cava, and tail artery and veins of the rat. We studied the concentration of vascular kininogenase in rats with one-kidney, one clip renovascular hypertension and in unilaterally nephrectomized normotensive rats. Six weeks after surgery, active and total vascular kininogenase activity (active plus trypsin-activated) was measured. Blood pressure was 212 +/- 4 mm Hg in the hypertensive rats (n = 33) and 120 +/- 1 mm Hg in the normotensive rats (n = 32) (p less than 0.001). Active kininogenase was lower in the hypertensive rats; although the difference was not significant in the thoracic aorta (56 +/- 8 versus 77 +/- 15), it was highly significant in the abdominal aorta (63 +/- 13 versus 167 +/- 17, p less than 0.001) and tail artery (48 +/- 8 versus 197 +/- 31, p less than 0.003). Total vascular kininogenase activity (active plus trypsin-activated) was lower in the hypertensive rats in all arteries examined: thoracic aorta (183 +/- 16 versus 380 +/- 38, p less than 0.003), abdominal aorta (565 +/- 61 versus 1,093 +/- 74, p less than 0.001), and tail artery (532 +/- 112 versus 1,243 +/- 135, p less than 0.003). Active kininogenase in the vena cava was higher in the hypertensive rats (213 +/- 56 versus 131 +/- 31); however, this difference was not statistically significant, whereas in the tail veins it was highly significant (1,803 +/- 221 versus 771 +/- 79, p less than 0.003).(ABSTRACT TRUNCATED AT 250 WORDS) .A Nolly H; Carretero OA; Scicli G; Madeddu P; Scicli AG. .I 275234 .U 91007876 .S Hypertension 9101; 16(4):441-51 .M Animal; Autonomic Nervous System/PH; Blood Pressure/DE; Captopril/PD; Dogs; Hypertension, Renal/*ET; Kidney/PP; Pentolinium Tartrate/PD; Renal Artery Obstruction/*CO/PP; Renal Circulation/DE; Renin/BL; Support, Non-U.S. Gov't; Vascular Resistance/DE. .T Development of hypertension from unilateral renal artery stenosis in conscious dogs. .P JOURNAL ARTICLE. .W The renal and systemic changes after stenosis of the left renal artery (n = 5) or sham stenosis (n = 6) in conscious dogs were studied sequentially over 25 days. Stenosis produced a prompt rise in arterial pressure, which was at all times due to reduced peripheral vascular conductance, with no increase in cardiac output despite initial evidence of mild fluid retention. The decrease in peripheral conductance was attributable to 1) the stenotic kidney (25% of the total and due to the mechanical effect of the stenosis itself), 2) the nonstenotic kidney (about 15% of the total and not caused by angiotensin II), and 3) the nonrenal vasculature (60%). The decrease in conductance in the nonrenal vasculature was due partly to angiotensin II, but there was also a gradually developing non-angiotensin II component. Acute administration of captopril caused significantly greater changes in arterial pressure and peripheral conductance throughout the period of stenosis than before stenosis (and greater than in sham-stenosis dogs), indicating that angiotensin II was constricting the peripheral vasculature even when plasma renin levels were no longer elevated. In the stenotic kidneys, captopril produced a fall in renal vascular resistance, but renal blood flow did not rise because there was an approximately equal rise in the resistance of the stenosis. There was no evidence for a role for the autonomic nervous system in the hypertension, as ganglion blockade (pentolinium) had similar hemodynamic effects before and after stenosis. Thus, the hypertension was due at all times to reduced peripheral conductance, with the two kidneys responsible for 40% of this reduced conductance. .A Anderson WP; Ramsey DE; Takata M. .I 275235 .U 91007877 .S Hypertension 9101; 16(4):452-61 .M Animal; Blood Pressure/DE; Calcium Channel Blockers/*PD; Captopril/*PD/TU; Comparative Study; Glomerular Filtration Rate; Hypertension/*CO/DT; Kidney Failure, Chronic/PC; Kidney Glomerulus/*DE/PA; Male; Nephrectomy; Proteinuria/UR; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Thiazepines/*PD/TU; Triglycerides/BL. .T Comparison of converting enzyme inhibitor and calcium channel blocker in hypertensive glomerular injury. .P JOURNAL ARTICLE. .W The protective effect of converting enzyme inhibitors in experimental hypertensive glomerular injury is associated with decreased systemic arterial and glomerular capillary pressure. Although calcium channel blockers effectively lower systemic blood pressure, their effect on glomerular capillary pressure and on hypertensive glomerular injury is uncertain. We compared equihypotensive treatment with the calcium antagonist TA 3090 or the converting enzyme inhibitor captopril in post-salt hypertensive Dahl salt-sensitive (DS) rats for up to 5 weeks after five sixths nephrectomy. Before the nephrectomy, all rats demonstrated hypertension (mean 177 mm Hg), proteinuria (mean 175 mg/day), and mild glomerulosclerosis (mean injury score 35). Rats treated with captopril or TA 3090 demonstrated a significant and equivalent decrease in systolic blood pressure compared with untreated rats at 2, 3, and 5 weeks after five sixths nephrectomy; however, only captopril reduced proteinuria. Final proteinuria was actually increased in rats treated with TA 3090 compared with untreated rats. Glomerular injury score was significantly decreased in captopril-treated compared with untreated rats at 2 weeks (33 +/- 9 versus 117 +/- 10, p less than 0.05) and 5 weeks (46 +/- 9 versus 94 +/- 24, p less than 0.05), whereas treatment with TA 3090 delayed but did not prevent progressive glomerular injury (2-week score 35 +/- 7, p less than 0.05 versus untreated; 5-week score 109 +/- 19, p = NS versus untreated). Thus, in hypertensive DS rats after subtotal nephrectomy, treatment with a converting enzyme inhibitor reduced systemic blood pressure, proteinuria, and glomerulosclerosis. However, equihypotensive treatment with a calcium channel blocker did not reduce proteinuria and delayed but did not prevent glomerulosclerosis. Thus, in the rat similar reductions in systemic blood pressure with these two classes of agents have disparate effects on the progression of chronic renal failure. .A Tolins JP; Raij L. .I 275236 .U 91007878 .S Hypertension 9101; 16(4):462-7 .M Adrenal Glands/*PH; Age Factors; Androgens/PH/*UR; Blood Pressure/*; Caucasoid Race; Child; Dehydroepiandrosterone/AA/BL; Female; Human; Male; Negroid Race; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Adrenal androgen excretion during adrenarche. Relation to race and blood pressure. .P JOURNAL ARTICLE. .W We have previously shown that black children have higher blood pressures than white children. In the present study, we examined whether a possible racial difference in adrenal androgen production during adrenarche might contribute to the racial disparity in blood pressure. Adrenal androgen production was estimated from urinary excretion of adrenal androgen metabolites that showed cross-reactivity with antisera to dehydroepiandrosterone sulfate (DHEA-S). Urine samples were collected overnight in 798 children, one third of whom were black. Analyses were performed for two different age groups, less than 10 years and 10 years or more of age. In children less than 10 years of age, adrenal androgen excretion rates were 17% higher in blacks than in whites (p = 0.0099); adrenal androgen excretion rates tended to be higher in older black children as well, but differences here were not statistically significant. Adrenal androgen excretion rates were positively correlated with diastolic blood pressure in the older age group only (p = 0.014). However, when the relation of race to blood pressure was examined along with adrenal androgen excretion adjusted for age, sex, and weight, race remained an independent contributor to the level of blood pressure, suggesting that a difference in adrenal androgens could not explain the racial differences in blood pressure. In summary, black children produced more adrenal androgen, but this did not explain their higher blood pressures. In older children, where adrenal androgen excretion rates were higher, diastolic blood pressure and adrenal androgen excretion were positively related, suggesting that adrenal androgens participate in establishing the level of blood pressure in young people. .A Pratt JH; Manatunga AK; Wagner MA; Jones JJ; Meaney FJ. .I 275237 .U 91007879 .S Hypertension 9101; 16(4):468-71 .M Animal; Blood Pressure/DE; Hypertension/ET/*TH; Interleukin-2/AD/*TU; Male; Rats; Rats, Inbred SHR; Recombinant Proteins/TU; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Interleukin-2 does not attenuate hypertension in spontaneously hypertensive rats. .P JOURNAL ARTICLE. .W It was recently reported that interleukin-2, when administered as a single bolus injection (5,000 units/kg), could prevent the development of hypertension in young spontaneously hypertensive rats and lower blood pressure to normotensive levels in spontaneously hypertensive rats with established hypertension. Consequently, efforts were made to duplicate this finding. Male spontaneously hypertensive rats (35 days old) were injected subcutaneously with 50,000 units/kg (3,500 units/rat) of recombinant interleukin-2 (Amgen) and had systolic blood pressure measured twice weekly by the tail-cuff technique. Systolic blood pressure in the interleukin-2-treated group was not significantly different from the vehicle-treated control group at any time point over 32 days of follow-up. A second injection of recombinant interleukin-2 (5,000 units/kg) was administered 32 days after the first injection. Again, no reduction in blood pressure was observed in the interleukin-2-treated group over an additional 38 days. Mean arterial pressure (+/- SEM) measured via intra-arterial cannula in conscious rats at age 105 days (38 days after the second treatment) was 168.5 +/- 3.5 mm Hg in interleukin-2-treated spontaneously hypertensive rats and 170.3 +/- 3.6 mm Hg in vehicle-treated controls. Both recombinant interleukin-2 preparations conformed to their respective manufacturer's indicated specific activity as determined by the ability of the interleukin-2 to induce proliferation of the interleukin-2-dependent cell line HT-2. Thus, this study demonstrated that interleukin-2 was ineffective in preventing or attenuating hypertension in spontaneously hypertensive rats. .A Pascual DW; Jin HK; Bost KL; Oparil S. .I 275238 .U 91007880 .S Hypertension 9101; 16(4):472-5 .M History of Medicine, 20th Cent.; Human; Hypertension/DT/*HI; Support, U.S. Gov't, Non-P.H.S.; United States; United States Department of Veterans Affairs/HI. .T Reminiscences of the Veterans Administration trial of the treatment of hypertension. .P CLINICAL TRIAL; HISTORICAL ARTICLE; JOURNAL ARTICLE; MULTICENTER STUDY. .A Freis ED. .I 275239 .U 91008369 .S Heart Lung 9101; 19(5 Pt 1):21A, 24A, 26A-27A .M Ethics, Medical; Ethics, Nursing; Euthanasia, Passive/*; Human; Life Support Care/*LJ; Patient Advocacy; Societies, Nursing; United States. .T Who lives, who dies, who decides? .P JOURNAL ARTICLE. .W The financial costs of the ethical dilemmas in the health care industry are profound, and the emotional ramifications for the patient and family are even more costly. As critical care nurses and as health care consumers, we must create an impetus for change. We need to ensure that we contribute to the quality of life while dealing with the conflicting values inherent in the right-to-die question. Together, we can create an ethical practice environment for ourselves, our families, and the patients for whom we care. .A Evans SA. .I 275240 .U 91008370 .S Heart Lung 9101; 19(5 Pt 1):439-44 .M Adult; Critical Care/*; Education, Nursing, Continuing/*; Female; Health Facility Environment; Human; Intensive Care Units; Job Satisfaction; Male; Middle Age; Nursing Staff, Hospital/PX; Preceptorship/*; Social Support; Teaching. .T Study of educational experiences, support, and job satisfaction among critical care nurse preceptors. .P JOURNAL ARTICLE. .W Experienced critical care staff nurses are frequently called to serve as clinical preceptors for nurses and nursing students who are unfamiliar with the critical care unit. These critical care nurse preceptors require educational preparation, continuing education, and support for their role. This descriptive correlational study surveyed 73 critical care nurse preceptors at 10 teaching hospitals in a metropolitan area in the Midwest. Forty-eight (65.8%) participants reported receiving some type of educational experience to prepare them for the role of preceptor. Only 24.7% of the respondents, however, participated in continuing education experiences related to the preceptor role. Job satisfaction was measured with a 48-item Likert scale developed for nurses by Slavitt et al. No significant differences in job satisfaction were reported for preceptors who received educational preparation and those who did not. However, the type of unit in which the preceptor worked did affect job satisfaction. Critical care preceptors in units classified as intermediate care and emergency departments had greater levels of job satisfaction than nurses working in intensive care units (t[68] = 2.52, p = 0.01). In addition, the longer the preceptor worked in critical care, the lower the level of job satisfaction (r = -0.210, p = 0.04). Job satisfaction was also influenced by the support preceptors received from their institution; a significant positive correlation was seen between this support and the level of job satisfaction. A description of the format and content of preparation programs for critical care preceptors was also provided as a result of this study. .A Bizek KS; Oermann MH. .I 275241 .U 91008371 .S Heart Lung 9101; 19(5 Pt 1):445-51 .M Adult; Arousal/PH; Energy Metabolism/*; Female; Heart Rate/PH; Human; Infant, Newborn; Infant, Premature/*PH/PX; Motor Activity; Skin Temperature; Sleep/*PH; Support, Non-U.S. Gov't. .T Energy conservation during skin-to-skin contact between premature infants and their mothers. .P JOURNAL ARTICLE. .W The effects of skin-to-skin contact on three indexes of energy expenditure: heart rate, activity level, and behavioral state, were examined in a pilot study. It was hypothesized that skin-to-skin contact, because of its soothing effects, would increase sleep, lower activity level, and reduce heart rate. Eight healthy preterm infants in a neonatal intensive care unit, who had reached 34 to 36 weeks gestation, experienced one session of skin-to-skin contact for an interfeeding interval. Observations were made once each minute using continuous videotape throughout three consecutive interfeeding intervals (before, during, and after skin-to-skin contact). Significant treatment effects were found by repeated-measures analysis of variance for behavioral state and activity level; pair-wise comparisons showed that quiet sleep frequency was significantly increased and activity level reduced during skin-to-skin contact. Infants had longer durations of quiet sleep during skin-to-skin contact. The Pearson product-moment correlation between heart rate and behavioral state was robust and generally linear, supporting use of heart rate as a measure of energy expenditure in these subjects. The findings suggest that skin-to-skin contact is a simple, cost-effective intervention that reduces activity and state-related energy expenditure. .A Ludington SM. .I 275242 .U 91008372 .S Heart Lung 9101; 19(5 Pt 1):452-5 .M Conflict (Psychology); Decision Making/*; Human; Intensive Care Units/*OG; Medical Directors/*; Nursing Staff, Hospital/*PX; Patient Admission; Patient Discharge; Perception; Questionnaires; Triage/*. .T Nursing perception of the availability of the intensive care unit medical director for triage and conflict resolution. .P JOURNAL ARTICLE. .W The Joint Commission on the Accreditation of Healthcare Organizations and the Society of Critical Care Medicine call on the physician medical director of the intensive care unit (ICU) to play an important role in admission and discharge decision-making. To assess nursing perception of the medical director's involvement in this decision-making, we analyzed data from a questionnaire administered at an annual ICU management conference to ICU nursing supervisors representing 101 hospitals and 137 ICUs. We asked nurses if the medical director or his or her designee (excluding residents) was available at night for triage, admission decision-making, and conflict resolution. In 21% (29) of the ICUs, nurses perceived no medical director at all. In the 54 ICUs with full-time medical directors, nurses in approximately 30% of the units said that there was no nighttime availability of the medical director or designee. The data suggest that many ICUs lack physician leadership in ICU management and resource allocation. .A Strosberg MA; Teres D; Fein IA; Linsider R. .I 275243 .U 91008373 .S Heart Lung 9101; 19(5 Pt 1):456-62 .M Aged; Assertiveness; Clinical Nursing Research; Exercise Therapy; Female; Human; Lung Diseases, Obstructive/*PX/RH; Male; Middle Age; Motivation; Patient Education; Pilot Projects; Psychotherapy, Group; Self Concept/*; Semantic Differential; Sex Counseling. .T Changes in self-concept during pulmonary rehabilitation, Part 1. .P JOURNAL ARTICLE. .W The purpose of this two-part study was to describe changes in self-concept during and after a formal pulmonary rehabilitation program. A 20-item semantic meaning differential scale was administered to 37 patients with severe chronic obstructive pulmonary disease who were participating in a multidisciplinary pulmonary rehabilitation program. Patients were asked to evaluate their past, present, and future selves on program admission, on program discharge, and 2 to 6 months after home discharge. Mean total self-concept score for the present self significantly increased between program admission and home discharge 3 weeks later (mean change 31.32 +/- 22.04, p less than 0.0001). No significant declines in self-concept were found 2 to 6 months after home discharge (p = 0.39). Men showed a significantly higher change in total self-concept score than women during the 3-week program (p = 0.03). However, the men's change score dropped significantly after home discharge (p = 0.02), suggesting a need for more intensive follow-up care than with women. The self-concept tool in this study provided an easy way to monitor subjective changes in psychologic status. .A Kersten L. .I 275244 .U 91008374 .S Heart Lung 9101; 19(5 Pt 1):463-70 .M Aged; Counseling/*; Depression; Emotions; Female; Follow-Up Studies; Human; Lung Diseases, Obstructive/*PX/RH; Male; Middle Age; Motivation; Patient Discharge; Program Evaluation/*; Self Assessment (Psychology); Self Concept/*. .T Changes in self-concept during pulmonary rehabilitation, Part 2. .P JOURNAL ARTICLE. .W This two-part study describes changes in self-concept during pulmonary rehabilitation. A 20-item semantic meaning differential scale was administered to 37 patients with severe chronic obstructive pulmonary disease who were participating in a multidisciplinary pulmonary rehabilitation program. Patients were asked to evaluate their past, present, and future self-concepts on program admission, on program discharge, and 2 to 6 months after home discharge. In this part of the study item-level quantitative data as well as qualitative data from the counseling session at program discharge are reported. The quantitative data documented detailed changes in self-concept at various stages of pulmonary rehabilitation. Counseling session results indicated that patient involvement in item-level analysis greatly facilitates psychosocial intervention. Findings from this study establish clinical indications for use of the Self-concept Evaluation tool in adult patients with chronic obstructive pulmonary disease. Use of this tool is recommended early in the rehabilitation process. .A Kersten L. .I 275245 .U 91008375 .S Heart Lung 9101; 19(5 Pt 1):471-3 .M Cardiovascular Diseases/*RH; Clinical Nursing Research; Convalescence; Human; Support, Non-U.S. Gov't. .T Recovery after cardiovascular events. Overview. .P JOURNAL ARTICLE. .A Gortner SR; Jenkins LS. .I 275246 .U 91008376 .S Heart Lung 9101; 19(5 Pt 1):474-80 .M Adult; Aged; Anxiety/PP; Arousal/*PH; Blood Pressure; Clinical Nursing Research; Coronary Disease/NU/*PP/PX; Female; Heart Rate; Heart Valve Diseases/NU/*PP/PX; Human; Male; Middle Age; Neural Transmission; Support, U.S. Gov't, P.H.S.; Touch/*. .T Effects of differential touch on nervous system arousal of patients recovering from cardiac disease. .P JOURNAL ARTICLE. .W Previous research suggests that the neural properties of certain types of touch as well as their perceived significance to the disease state may be related to heightened activation of the nervous system. In this study the effects of different types of touch on nervous system arousal were examined in 59 adult patients who were receiving treatment for coronary artery disease. They were exposed to a standardized protocol that systematically varied the neural properties and procedural nature of the touch received. Measures of cardiovascular reactivity (heart rate and rhythm data as well as blood pressure measurements) and state anxiety were used as indexes of arousal. The results indicated that all types of touch evoked heart rate deceleration in contrast to both baseline and verbal conditions. However, there were no differential effects related to either the neural properties or procedural nature of touch. Diastolic blood pressure and state anxiety were also lower as a result of the touch. No changes were observed for systolic blood pressure or heart rhythm. In general, findings suggested that touch served to reduce arousal rather than to produce negative psychophysiologic consequences for recovery. .A Weiss SJ. .I 275247 .U 91008377 .S Heart Lung 9101; 19(5 Pt 1):481-5 .M Affect; Aged; Cohort Studies; Comparative Study; Coronary Artery Bypass/MO/PX/*RH; Female; Heart Valve Prosthesis/MO/PX/*RH; Human; Male; Middle Age; Prospective Studies; Questionnaires; Sex Factors; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Differences in recovery from cardiac surgery: a profile of male and female patients. .P JOURNAL ARTICLE. .W The specific aim of this study is to compare and contrast the biophysical and psychosocial profile of men and women undergoing cardiac surgery (coronary artery bypass graft and valve replacement) during the perioperative and home recovery period. Coronary artery disease appears to be qualitatively worse in women than men although the prevalence in women does not approach that in men until the seventh decade. Valvular disorders also reveal a different profile by sex with the greater valvular problems in women related to the fact that women have more rheumatic heart disease. A prospective, longitudinal design with a convenience sample of 117 patients undergoing cardiac surgery and their spouses (234 subjects) from five Northern California hospitals was used to tap patient response at three critical perioperative data points. Female patients were observed during the perioperative period to have significantly more shortness of breath, poorer cardiac functional status (New York Heart Association), significantly longer intensive care unit stays, and proportionately more deaths. At 1 and 3 months after discharge, however, their recoveries did not differ significantly from men's when they were compared on sexuality, recreation, or return-to-work variables. Surprisingly, female patients had significantly less mood disturbances as measured by the Profile of Mood States than their male counterparts, and they scored higher on measures of family satisfaction than did male patients. Implications of the study involve early recognition of heart disease in women, preparation of families for longer intensive care unit stays, and appreciation of different psychosocial responses to surgery. .A Rankin SH. .I 275248 .U 91008378 .S Heart Lung 9101; 19(5 Pt 1):486-90 .M Adaptation, Psychological/*; Attitude to Health; Chronic Disease/PX; Emotions; Family/*PX; Human; Interpersonal Relations; Longitudinal Studies; Psychological Tests; Psychological Theory; Vascular Surgery/*PX/RH. .T Family recovery after vascular surgery. .P JOURNAL ARTICLE. .W Twenty-one families were observed in a 3-month study to assess family coping with major vascular surgery and recovery. Analysis of family measures data (the Family APGAR, the Family Inventory of Resource for Management, and the Family Crisis Oriented Personal Evaluation Scales) was combined with grounded theory method to assess family responses over time and recovery outcomes. Containment emerged as the major conceptual category of the grounded theory. Containment refers to a constellation of constructed meanings for events and behavioral responses used by families to regulate the impact of the surgical crisis and reduce family disruption. This "contained" coping pattern was manifested in families' avoidant behaviors and narrow definitions of the problem: that is, they defined their situation in terms of the surgical repair as cure rather than palliative intervention for a chronic, progressive disease. Situational factors such as the insidious development of the illness and the primary focus of care providers in the hospital on surgical care (allowing families' narrow definitions of their situation to remain unchallenged) also contributed to containment. Containment resulted in poor risk factor management as a major recovery outcome. Isolation and family conflict were evident throughout the recovery period. Concerns generated by continued evidence of morbidity during recovery contributed to a developing awareness of underlying disease, and diminishing containment when this growing awareness was openly shared within the family. Significant findings of the family measures analysis were compared with the grounded theory of the qualitative data. Each corroborated the other in key dimensions. .A Leavitt MB. .I 275249 .U 91008379 .S Heart Lung 9101; 19(5 Pt 1):491-9 .M Adaptation, Psychological; Convalescence; Empathy; Female; Heart Surgery/NU/PX/*RH; Human; Longitudinal Studies; Male; Middle Age; Nursing Assessment/*; Patient Education/*; Postoperative Period; Prospective Studies; Referral and Consultation; Social Support; Support, U.S. Gov't, P.H.S.. .T Nurse-monitored cardiac recovery: a description of the first 8 weeks. .P JOURNAL ARTICLE. .W Health problems and related patient management during early recovery after cardiac surgery are not well documented. As part of a larger study of recovery from cardiac surgery 75 patient-care giver pairs received telephone calls from nurses at 1, 2, 3, 4, 6, and 8 weeks after discharge for the purpose of intervening to facilitate early recovery at home. After each call, nurses recorded detailed notes on the patients' progress and concerns. Content analysis of detailed nurses' recordings revealed the following predominant nursing actions: assessment, provision of support, reinforcement of predischarge teaching, referrals, and teaching. The five nursing diagnoses that occurred most frequently across the 8-week recovery period were altered comfort: pain; ineffective coping, individual; activity intolerance; sleep pattern disturbance; and altered nutrition. In response to these problems, patients managed and prevented health-related problems and engaged in health promotional and normalizing activities. By anticipating common problems in recovery, patients and care givers can be better prepared for going home. Similarly nurses can be better prepared to anticipate and respond to common recovery problems. .A Tack BB; Gilliss CL. .I 275250 .U 91008380 .S Heart Lung 9101; 19(5 Pt 1):500-4 .M Aged; Case Report; Combined Modality Therapy; Electrocardiography; Human; Male; Myocardial Infarction/*NU/PP/TH; Nursing Diagnosis; Torsades de Pointes/*NU/PP/TH. .T Torsade de pointes: a critical care nurse's dilemma. .P JOURNAL ARTICLE. .W Torsade de pointes is a polymorphous ventricular tachycardia characterized by a gradual change in the direction of the QRS complex. Because critical care nurses are the first to recognize arrhythmias, they require the knowledge and skill to intervene appropriately. This case report focuses on identification of the characteristics, contributing factors, therapeutic modalities, and relevant nursing diagnoses for the patient with torsade de pointes. .A Wines LM; Macari-Hinson MM. .I 275251 .U 91008381 .S Heart Lung 9101; 19(5 Pt 1):505-11 .M Angiotensin-Converting Enzyme Inhibitors/PD/PK/*TU; Captopril/TU; Enalapril/TU; Heart Failure, Congestive/*DT/PP; Hemodynamics/DE; Human; Multicenter Studies; Renin-Angiotensin System/DE/PH. .T Role of angiotensin-converting enzyme inhibitors in congestive heart failure. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Conventional therapy for congestive heart failure (CHF) includes sodium-restricted diet, diuretics, digitalis, vasodilators, and short-term intravenous administration of beta-adrenergic agonists during episodes of decompensation. A specific class of vasodilators, the angiotensin-converting enzyme inhibitors, has recently gained predominance in the treatment of congestive heart failure. The primary mechanism of action is to reduce production of angiotensin II by competitive inhibition of the enzyme that converts angiotensin I into angiotensin II. Reduced levels of angiotensin II, in turn, promote vasodilation and lower aldosterone production. The benefits of angiotensin-converting enzyme inhibitor therapy in chronic congestive heart failure have been demonstrated by improvement in left ventricular performance, exercise capacity, functional status (using New York Heart Association classification), and survival. .A Galvao M. .I 275252 .U 91008382 .S Heart Lung 9101; 19(5 Pt 1):514-23 .M Adolescence; Adult; Aged; Anticoagulants/TU; Child; Emergencies; Extracorporeal Membrane Oxygenation/*/AE/IS/NU; Female; Heart Arrest/*TH; Hemorrhage/ET; Human; Infection/ET; Kidney Failure, Acute/ET; Male; Middle Age; Respiration, Artificial/MT; Shock, Cardiogenic/DT/*TH. .T Mechanical cardiopulmonary support for refractory cardiogenic shock. .P JOURNAL ARTICLE. .W From February 1982 to February 1990, 38 patients (30 male patients and 8 female patients) ranging in age from 10 to 78 years (mean 49.4 years) have been supported with arteriovenous extracorporeal membrane oxygenation (ECMO) at St. Louis University Medical Center as a resuscitative system for cardiac arrest or cardiogenic shock. All patients were unresponsive to conventional resuscitative measures including an intraaortic balloon pump in 25 patients. Patients were resuscitated in the intensive care unit, cardiac catheterization laboratory, or the emergency department. Diagnosis varied from acute myocardial infarctions (12 patients), ischemic disease (15 patients), end-stage cardiomyopathy (7 patients), congenital heart disease (3 patients), or postoperative cardiac transplant graft rejection (1 patient). Three patients could not be resuscitated with ECMO because of low flow, but the remaining 35 (92%) achieved hemodynamic stability with ECMO flows greater than 2 L/min/m2. Duration of support ranged from 0.5 to 130 hours (mean 28 hours). Twenty-four patients were successfully weaned from ECMO support after coronary artery bypass (five patients), cardiac transplantation (two patients), or ventricular assist device insertion (eight patients), or with inotropic support (nine patients). Of the 14 patients not weaned, three were inadequately resuscitated, two had percutaneous transluminal coronary angioplasty while receiving ECMO, and nine were not candidates for further intervention. Nine (24%) patients were discharged and are long-term survivors. Our results indicate that resuscitative ECMO is useful for intervals of 12 to 24 hours and can best be applied with (1) patients younger than 60 years of age; (2) patients having acute events (failed percutaneous transluminal coronary angioplasty) amenable to surgical intervention; and (3) candidates for cardiac transplantation who could be switched to more sophisticated devices within 12 to 24 hours of ECMO insertion. With these criteria, ECMO, when used as a resuscitative system, can result in increased survival in selected patients with refractory cardiogenic shock or cardiac arrest. .A Reedy JE; Swartz MT; Raithel SC; Szukalski EA; Pennington DG. .I 275253 .U 91008383 .S Heart Lung 9101; 19(5 Pt 1):526-33 .M Adult; Aged; Analgesia/MT; Clinical Nursing Research; Communication; Female; Human; Intensive Care Units/*; Interviews; Male; Middle Age; Pain/*DI/PX/TH; Pain Measurement/*; Pain, Postoperative/TH; Support, U.S. Gov't, P.H.S.. .T Pain experiences of intensive care unit patients. .P JOURNAL ARTICLE. .W The purpose of this study was to describe various dimensions of the pain experiences of intensive care unit (ICU) patients. A purposive, primarily surgical sample of 24 ICU patients from two hospitals was interviewed after transfer from ICU. All but one patient remembered their ICU stay. Although this and six other patients had no recall of pain, 63% of the sample rated their pain as being moderate to severe in intensity. In a subgroup of nine patients having cardiac surgery, mean morphine sulfate administration during the first three postoperative days was 14 mg/day. This group of patients reported a lack of total pain relief from analgesics. Patients also described various sources of their pain, difficulties they had in communicating their pain, and nonpharmacologic methods that helped relieve their pain. Results of this study clearly indicate that not only pain but its communication and treatment were significant problems for a substantial portion of this ICU sample. Further descriptive and experimental research of pain characteristics and treatment practices for ICU patients is urgently needed. Improvements in nursing practice that result from such research may make a substantial difference in the comfort and well-being of critically ill patients. .A Puntillo KA. .I 275254 .U 91008384 .S Heart Lung 9101; 19(5 Pt 1):534-6 .M Case Report; Cefotaxime/TU; Escherichia coli Infections/*/DT; Female; Fungi/*IP; Human; Meningitis/DT/*MI; Middle Age. .T Fungal pseudomeningitis superimposed on Escherichia coli meningitis. .P JOURNAL ARTICLE. .W Pseudomeningitis is the demonstration of microorganisms from the cerebrospinal fluid by stain or culture in a patient with symptoms suggesting meningitis. This is a report of fungal pseudomeningitis superimposed on a case of nosocomial Escherichia coli meningitis resulting from a neurosurgical procedure. Critical care personnel need to be aware of the possibility of pseudomeningitis with or without associated meningitis in the appropriate setting. .A Gelfand MS; Schoch PE; Cunha BA. .I 275255 .U 91008385 .S Heart Lung 9101; 19(5 Pt 1):537-9 .M Data Collection/*MT; Data Interpretation, Statistical; Nursing Research/*MT; Research Design/ST. .T Evaluating sources for secondary analysis. .P JOURNAL ARTICLE. .W Secondary analysis can be extremely versatile in understanding change of phenomena and extending previous studies. However, all data are not created equal. When using secondary sources, it is important to evaluate the data, weigh potential biases, and adopt an attitude of healthy skepticism. Although the potentials of secondary analysis are enormous, certain problems can be avoided if sources are evaluated carefully. Nurse researchers should be aware of some limitations of secondary data sets. Expert knowledge of research designs and statistical techniques, in addition to an open and creative mind, will be invaluable assets in answering the preceding eight questions. .A Leske JS. .I 275256 .U 91008386 .S Heart Lung 9101; 19(5 Pt 1):540-1 .M Critical Care; Empathy/*; Ethics, Nursing/*; Human; Nurse-Patient Relations/*; Patient Advocacy. .T Ethical issues in critical care. Real presence. .P JOURNAL ARTICLE. .A Marsden C. .I 275257 .U 91008387 .S Heart Lung 9101; 19(5 Pt 2):547-80 .M Critical Care/*MT; Human; Monitoring, Physiologic/*; Oximetry/*; Oxygen Consumption/*; Support, Non-U.S. Gov't. .T SvO2 monitoring: research and clinical applications. Symposium proceedings based on the Pre-National Teaching Institute (NIT) Conference held by the American Association of Critical-Care Nurses. San Francisco, California, May 20, 1990. .P CONGRESS; OVERALL. .I 275258 .U 91008388 .S Heart Lung 9101; 19(5 Pt 2):548-51 .M Critical Care/*MT; Evaluation Studies; Human; Nursing Care/*MT; Oximetry/IS/*MT; Oxygen Consumption/*; Support, U.S. Gov't, P.H.S.. .T The physiologic basis for continuous mixed venous oxygen saturation monitoring. .P JOURNAL ARTICLE. .W Critically ill patients often have conditions that reduce oxygen delivery and increase oxygen demand. Routine nursing care, such as suctioning, positioning, and bathing, also increases the patient's oxygen demand. If the patient's oxygen demand exceeds the supply, dysrhythmias, hypotension, altered level of consciousness, and other adverse responses can occur. We describe use of continuous monitoring of mixed venous oxygen saturation (SvO2) as a tool to assess the patient's supply/demand balance during nursing care. The physiology of oxygen transport is reviewed, and oxygen delivery, reserve, and consumption are defined. Conditions that decrease oxygen delivery and increase oxygen demand are discussed, and the effects on SvO2 are illustrated. With continuous SvO2 monitoring, critical care nurses can see the effect of their nursing care on the patient's oxygenation and can adjust their care according to the patient's tolerance. .A White KM; Winslow EH; Clark AP; Tyler DO. .I 275259 .U 91008389 .S Heart Lung 9101; 19(5 Pt 2):552-7 .M Adult; Anoxemia/PC; Comparative Study; Critical Care/*MT/PX; Evaluation Studies; Heart Rate/*PH; Human; Intubation, Intratracheal; Middle Age; Nursing Care/*MT; Oximetry/*; Oxygen Consumption/*; Oxygen Inhalation Therapy; Respiration, Artificial; Sampling Studies; Suction/AE/*MT; Support, U.S. Gov't, P.H.S.; Time Factors. .T Effects of endotracheal suctioning on mixed venous oxygen saturation and heart rate in critically ill adults. .P CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY. .W The purpose of this multisite study was to determine the effects of endotracheal suctioning on mixed venous oxygen saturation (SvO2) and heart rate in 189 critically ill adults. One-pass, intermittent suction was applied for 10 or fewer seconds, with three prehyperoxygenation and three posthyperoxygenation breaths of 100% oxygen. Subjects at three hospitals (n = 127) underwent suctioning using hyperoxygenation with anesthesia bags and traditional suction catheters (open suction method). Subjects at one hospital (n = 62) underwent suctioning with hyperoxygenation by ventilator and in-line suction catheters (closed suction method). For subjects from all hospital sites combined, the SvO2 decreased from 67% to 64% (p = 0.001), a 4% change from baseline, and returned to baseline within 2 minutes. However, in subjects receiving the open method of suction, SvO2 dropped from 66% to 62% immediately after suctioning and returned to baseline within 4 minutes. In contrast, when the closed suction method was used, SvO2 rose from 67.7% to 67.86% immediately after suctioning, drifting upward to 71% for the next 2 minutes before dropping toward the baseline after 4 minutes. Mean heart rate increased from a baseline of 99 beats/min to 104 beats/min immediately after suctioning (p = 0.001), a 5% change from baseline, and gradually returned to baseline over the next 4 minutes. No significant differences were seen in heart rate between subjects having the open versus closed suction method. In conclusion, the closed suction method showed a higher SvO2 after endotracheal suctioning compared with the open suction method (p = 0.0001). Some form of hyperoxygenation before and after endotracheal suctioning is recommended. .A Clark AP; Winslow EH; Tyler DO; White KM. .I 275260 .U 91008390 .S Heart Lung 9101; 19(5 Pt 2):557-61 .M Critical Care/*MT; Evaluation Studies; Female; Heart Rate/*PH; Human; Male; Middle Age; Nursing Care/*MT; Oximetry/*; Oxygen Consumption/*; Posture/*PH; Support, U.S. Gov't, P.H.S.; Time Factors; Ventilation-Perfusion Ratio. .T Effects of a lateral turn on mixed venous oxygen saturation and heart rate in critically ill adults. .P JOURNAL ARTICLE. .W The purpose of this study was to determine the effects of a lateral turn on mixed venous oxygen saturation (SvO2) and heart rate in 183 critically ill adults. Mean SvO2 decreased from a baseline of 67% to 61% saturation (p less than 0.0001) immediately after turning and gradually returned to 66% saturation (p less than 0.002) within 4 minutes. Mean heart rate increased slightly from a baseline of 99 beats/min to 102 beats/min (p less than 0.0001) immediately after turning and decreased slightly to 101 beats/min (p less than 0.0004) within 4 minutes. These statistically significant changes in SvO2 and heart rate were not clinically significant for most patients. However, physiologic responses to turning were highly variable. SvO2 reductions of 25% or more from baseline, heart rate increases and decreases of 10 beats/min or more, and signs of activity intolerance occurred in some patients. Nurses should expect critically ill patients to have a decrease in SvO2 of approximately 9% of baseline and small changes in heart rate after turning. These changes should be transient, with SvO2 and heart rate gradually returning toward baseline levels during the next 4 minutes. If turning triggers large or prolonged changes in SvO2 or heart rate, prompt repositioning and evaluation are needed to prevent adverse effects. .A Winslow EH; Clark AP; White KM; Tyler DO. .I 275261 .U 91008391 .S Heart Lung 9101; 19(5 Pt 2):562-5 .M Adult; Aged; Aged, 80 and over; Back; Critical Care/*MT; Evaluation Studies; Female; Heart Rate/*PH; Human; Male; Massage/*MT; Middle Age; Muscle Relaxation/*PH; Nursing Care/*MT; Oximetry/*; Oxygen Consumption/*; Posture/PH; Support, U.S. Gov't, P.H.S.; Time Factors. .T Effects of a 1-minute back rub on mixed venous oxygen saturation and heart rate in critically ill patients. .P CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY. .W In this study we evaluated mixed venous oxygen saturation (SvO2) and heart rate responses after a 1-minute back rub in 173 critically ill patients. The back rub was the third and last intervention in a study conducted in intensive care units at four hospitals. For this multiple-intervention study all patients were placed in a supine position to obtain baseline SvO2 and heart rate, then underwent suctioning via endotracheal tube, and were turned to a lateral position. After 15 minutes in a side-lying position, the subjects received a 1-minute back rub. Data were collected immediately after the back rub and at 1-minute intervals for 4 minutes. After the back rub, SvO2 decreased immediately from the mean baseline of 67% to 63% and gradually increased, returning to baseline by minute 4. The mean baseline heart rate of 99 beats/min increased to 103 beats/min immediately after the back rub and gradually decreased after massage, but remained higher than baseline by minute 4. Although the findings were statistically significant (p = 0.0001), these minimal physiologic changes do not represent clinical significance. Based on the findings, the back rub, a traditional nursing measure that can provide comforting touch, represented a minor stimulus affecting heart rate and oxygen demands in most critically ill patients. However, because of the variability found in heart rate and SvO2, individual responses need to be assessed. .A Tyler DO; Winslow EH; Clark AP; White KM. .I 275262 .U 91008392 .S Heart Lung 9101; 19(5 Pt 2):566-70 .M Adolescence; Adult; Aged; Cardiac Output; Cardiomyopathy, Congestive/ME/NU/*PP; Case Report; Catheters, Indwelling; Critical Care/*MT/PX; Evaluation Studies; Female; Human; Male; Oximetry/*; Oxygen Consumption/*; Postoperative Complications/ME/NU/*PP; Psychomotor Agitation/ME/NU/*PP; Time Factors. .T Evaluating oxygen delivery and oxygen utilization with mixed venous oxygen saturation monitoring: a case study approach. .P JOURNAL ARTICLE. .W Three cases studies are presented to demonstrate clinical application of mixed venous oxygen saturation (SvO2) monitoring in critical care nursing practice. Examples of critically ill patients are used to demonstrate how SvO2 monitoring can be used in clinical practice to reflect an imbalance between oxygen delivery and oxygen utilization. In the first case, the patient had a problem with oxygen delivery. Continuous SvO2 data aided nurses in guiding, adjusting, and assessing therapy. The second case demonstrates how SvO2 monitoring can provide an early sign of a life-threatening complication. The final case is one in which the patient had a problem with oxygen utilization. In all the cases, continuous SvO2 data provided important information about the balance between oxygen delivery and oxygen utilization. .A Gawlinski A; Henneman EA. .I 275263 .U 91008393 .S Heart Lung 9101; 19(5 Pt 2):570-4 .M Aged; Body Temperature; Cardiac Output; Coronary Artery Bypass/*NU; Critical Care/*MT; Evaluation Studies; Female; Human; Male; Middle Age; Oximetry/*; Oxygen Consumption; Postoperative Care/*MT; Support, Non-U.S. Gov't; Time Factors. .T Evaluation of the patient having cardiac surgery in the postoperative rewarming period. .P JOURNAL ARTICLE. .W Ensuring adequate oxygen delivery to the tissues with respect to oxygen demand is the treatment goal in patients undergoing coronary artery surgery (CAS). In this study we examined changes in temperature, arterial oxygen saturation (SaO2), cardiac index (CI), oxygen consumption (VO2), and mixed venous oxygen saturation (SvO2) over the initial 4-hour rewarming period in 36 patients having CAS. When patients were admitted to the intensive care unit the mean temperature was 36.27 degrees C, and it increased to 37.50 degrees C; SaO2 was 97.67% at the beginning and end of the 4-hour period; CI was 2.88 L/min/m2 and rose to 3.00 L/min/m2; VO2 was high at 0.320 L/min on admission and remained high at 0.290 L/min at the end of the 4-hour rewarming period; and SvO2 was 70.83% initially and declined to 66.53% in the same period of time. Continuous SvO2 monitoring was valuable in the ongoing assessment and management of the patients in stable, mildly hypothermic condition after CAS during the 4-hour postoperative rewarming period. .A Osguthorpe SG; Tidwell SL; Ryan WJ; Paull DL; Smith TL. .I 275264 .U 91008394 .S Heart Lung 9101; 19(5 Pt 2):574-8 .M Aged; Analysis of Variance; Comparative Study; Critical Care/*MT; Evaluation Studies; Human; Myocardial Revascularization/*NU; Oximetry/*; Oxygen Consumption/*; Postoperative Care/*MT; Posture/*PH; Random Allocation; Supination/PH; Support, Non-U.S. Gov't; Time Factors. .T Effects of position changes on mixed venous oxygen saturation in patients after coronary revascularization. .P JOURNAL ARTICLE. .W The purpose of this study was to investigate the effects of position changes on mixed venous oxygen saturation (SvO2) and to describe the mechanisms responsible for SvO2 changes reported to occur with position changes. The study was done from 4 to 8 hours after surgery in 34 patients after coronary artery bypass grafting. Subjects were put through a series of six position changes, including head of bed elevations and right and left lateral decubitus with return to supine between each. Each position was maintained for 30 minutes. SvO2, arterial oxygen saturation (SaO2), and oxygen consumption (VO2) were measured before and after each position change. Overall mean subject data demonstrated a decrease in SvO2 with each of the lateral position changes. The SvO2 did not drop below 60% in these mean data, and this drop returned to baseline by 5 minutes. There were no significant changes in the mean data for VO2 or SaO2. No significant correlation was found in the mean data between SvO2 and VO2 or SvO2 and SaO2 measurements. Trends were demonstrated in five specific cases that suggested a correlation between changes in SvO2 and changes in VO2 and SaO2. In conclusion, this study demonstrated that subjects were able to tolerate position changes with no clinically significant changes in SvO2, SaO2, or VO2. .A Tidwell SL; Ryan WJ; Osguthorpe SG; Paull DL; Smith TL. .I 275265 .U 91008395 .S Heart Lung 9101; 19(5 Pt 2):578-80 .M Blood Volume; Cardiac Output; Critical Care/*MT; Evaluation Studies; Hemoglobins/AN; Human; Nursing Care/*MT; Oximetry/*; Oxygen/BL/ME. .T Perspectives on the interpretation of continuous mixed venous oxygen saturation. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Continuous measurement of mixed venous oxygen saturation (SvO2) is a beneficial method for evaluating overall dynamic tissue oxygen balance in critically ill patients. Several important factors, however, may influence the accurate analysis of SvO2 data trends. In this review we highlight these factors and support cautious interpretation of SvO2 in conjunction with other available patient data and with strict attention to the clinical value and limitations of the parameter. .A Enger EL; Holm K. .I 275266 .U 91009397 .S J Bone Joint Surg [Br] 9101; 72(5):754-6 .M Bone Neoplasms/*DI; Human. .T Diagnosing malignant bone tumours [editorial] .P EDITORIAL. .A Grimer RJ; Sneath RS. .I 275267 .U 91009398 .S J Bone Joint Surg [Br] 9101; 72(5):757-60 .M Adult; Aged; Aged, 80 and over; Bone Cements/*; Female; Follow-Up Studies; Hip Joint/RA; Hip Prosthesis/*; Human; Male; Middle Age; Pain/PP; Prosthesis Failure; Reoperation. .T The effect of improved cementing techniques on component loosening in total hip replacement. An 11-year radiographic review. .P JOURNAL ARTICLE. .W Improved cementing techniques have been shown to decrease the rate of aseptic loosening of femoral components of cemented total hip replacements at five to seven years. We now report our results in 105 hips in 93 patients at 10 to 12.7 years (mean 11.2). The improved techniques included use of a medullary plug, a cement gun, a doughy mix of Simplex P and a collared stem of chrome cobalt. Only three femoral components had definitely loosened, none were probably loose and 24 were graded as possibly loose. In contrast, the incidence of radiographic loosening on the acetabular side was 42%. Improved cementing techniques have produced a marked reduction in the rate of aseptic loosening of the femoral component, but the incidence of acetabular loosening is unchanged. .A Mulroy RD Jr; Harris WH. .I 275268 .U 91009399 .S J Bone Joint Surg [Br] 9101; 72(5):761-4 .M Acetabulum/*IN; Adolescence; Adult; Aged; Aged, 80 and over; Female; Follow-Up Studies; Fractures/*SU; Hip Joint/RA; Hip Prosthesis/*; Human; Male; Middle Age; Prosthesis Failure; Recurrence; Reoperation; Retrospective Studies. .T Total hip arthroplasty after fracture of the acetabulum. Long-term results. .P JOURNAL ARTICLE. .W We made a retrospective study of 55 primary total hip arthroplasties in 53 patients with a history of previous acetabular fracture. The mean follow-up was 7.5 years and the average age at fracture was 48.7 years. The incidence of radiographic femoral loosening (29.4%), symptomatic loosening (15.7%), and femoral revision (7.8%) were similar to those previously reported at 10 years for routine arthroplasties by Stauffer (1982). On the acetabular side, the incidence of radiographic loosening (52.9%), symptomatic loosening (27.5%), and revision (13.7%) were four to five times higher. We conclude that a history of prior acetabular fracture has a significant adverse impact on the long-term outcome of any subsequent total hip arthroplasty. .A Romness DW; Lewallen DG. .I 275269 .U 91009400 .S J Bone Joint Surg [Br] 9101; 72(5):765-9 .M Acetabulum/PA/*RA; Adolescence; Adult; Cartilage/PA/*RA; Female; Follow-Up Studies; Human; Male; Middle Age; Osteoarthritis/CO/RA/*SU; Osteotomy/*MT; Pain/ET; Pelvic Bones/*SU; Prognosis. .T Chiari pelvic osteotomy for osteoarthritis. The influence of the torn and detached acetabular labrum. .P JOURNAL ARTICLE. .W We assessed the results of Chiari pelvic osteotomy in 64 hips with early osteoarthritis in terms of acetabular labral detachment detected pre-operatively by arthrography. At an average follow-up of four years, assessment by the Merle d'Aubigne score showed 83% excellent or good results. These satisfactory results were achieved in only half the cases with a detached labrum, but in nearly all cases with normal or torn acetabular labra. Other factors such as the acetabular index, the level and angle of osteotomy, and the displacement following osteotomy did not affect the results. Chiari pelvic osteotomy is a worthwhile procedure for early osteoarthritis in selected cases, but a detached acetabular labrum increases the risk of clinical failure. .A Nishina T; Saito S; Ohzono K; Shimizu N; Hosoya T; Ono K. .I 275270 .U 91009401 .S J Bone Joint Surg [Br] 9101; 72(5):770-1 .M Blood Loss, Surgical/*PC; Bone Cements; Bupivacaine; Female; Hip Prosthesis/*; Human; Lumbosacral Plexus; Nerve Block/*; Prospective Studies. .T Blood loss reduced during hip arthroplasty by lumbar plexus block. .P JOURNAL ARTICLE. .W We measured the blood loss during and after hip replacement in two groups of women, each consisting of 10 patients. In one group the lumbar plexus was infiltrated with bupivacaine, in the other it was not. The group in whom the plexus was blocked had significantly less blood loss. .A Twyman R; Kirwan T; Fennelly M. .I 275271 .U 91009402 .S J Bone Joint Surg [Br] 9101; 72(5):772-4 .M Activities of Daily Living; Adult; Aged; Arthritis, Rheumatoid/PA/PP/*SU; Female; Human; Knee Joint/PP; Knee Prosthesis/*; Length of Stay; Male; Middle Age; Postoperative Complications; Prospective Studies; Range of Motion, Articular; Reoperation. .T Simultaneous or staged bilateral total knee replacements in rheumatoid arthritis. A prospective study. .P JOURNAL ARTICLE. .W In a prospective study of 100 knee arthroplasties in patients with rheumatoid arthritis, simultaneous bilateral surgery was compared with staged bilateral replacements. All patients had improved function following their operations but those who had staged surgery only achieved maximum benefit after the second knee had been replaced. The complication rate was no greater for simultaneous surgery and we therefore advocate the method for those patients who require bilateral replacements. .A Stanley D; Stockley I; Getty CJ. .I 275272 .U 91009403 .S J Bone Joint Surg [Br] 9101; 72(5):775-8 .M Arthritis, Rheumatoid/PP/SU; Female; Follow-Up Studies; Human; Knee Joint/PP/RA; Knee Prosthesis/*; Male; Middle Age; Postoperative Complications; Prosthesis Design; Prosthesis Failure; Range of Motion, Articular; Reoperation; Wound Healing/PH. .T The Oxford knee replacement. A review from an independent centre. .P JOURNAL ARTICLE. .W We present a study of 67 Oxford bicompartmental total knee replacements performed at a district general hospital. In this general orthopaedic unit, 57 of the knees (85%) had significant relief of pain with a mean flexion range of 95 degrees and a mean flexion deformity of only 9 degrees. There was a noticeable difference between osteoarthritic and rheumatoid knees. Poor results could be directly related to an avoidable postoperative complication. The results of this independent assessment may be compared favourably with the previously published series from the specialist centre at which the prosthesis was designed. .A Barrett DS; Biswas SP; MacKenney RP. .I 275273 .U 91009404 .S J Bone Joint Surg [Br] 9101; 72(5):779-83 .M Aged; Aged, 80 and over; Arthritis/SU; Arthritis, Rheumatoid/SU; Body Weight; Bone Cements/*; Comparative Study; Female; Human; Hypertension/EP; Incidence; Knee Prosthesis/*AE; Male; Middle Age; Osteoarthritis/SU; Phlebography; Thrombophlebitis/*EP/ET/RA; Tuberculosis, Osteoarticular/SU. .T The incidence of deep vein thrombosis after cementless and cemented knee replacement. .P JOURNAL ARTICLE. .W The incidence of deep vein thrombosis in 244 patients who had total knee replacement has been studied. In 120 the prosthesis was cemented and in 124 it was cementless. In all cases the replacement was primary and a porous-coated prosthesis with a porous-coated central tibial stem was used. Deep vein thrombosis was diagnosed by venography, and pulmonary embolism by perfusion scanning. The incidence of deep vein thrombosis in the cementless knees (23.8%) and in the cemented (25%) was approximately the same. The only significant predisposing factors for deep vein thrombosis in both groups were obesity, prolonged postoperative immobilisation, previous venous disease and hyperlipidaemia. .A Kim YH. .I 275274 .U 91009405 .S J Bone Joint Surg [Br] 9101; 72(5):784-7 .M Age Factors; Aged; Aged, 80 and over; Comparative Study; Female; Femoral Neck Fractures/*SU; Fracture Fixation, Internal; Hip Prosthesis/*; Human; Male; Middle Age; Reoperation. .T Secondary total hip replacement after fractures of the femoral neck. .P JOURNAL ARTICLE. .W We studied the rate of revision in 84 consecutive total hip replacements performed for failed osteosynthesis of femoral neck fractures and compared it with that for primary arthroplasty for osteoarthritis. The age and sex adjusted risk of prosthetic failure was 2.5 times higher after failure of fixation, but all the excess risk was in patients over 70 years of age. There were radiographic signs of loosening of the femoral component at five to 12 years after secondary arthroplasty in six of 33 survivors. In general, the results of secondary replacement were no worse than those obtained after primary arthroplasty for femoral neck fracture. We consider that internal fixation should be the primary procedure: total hip replacement is a safe secondary procedure when osteosynthesis fails. .A Franzen H; Nilsson LT; Stromqvist B; Johnsson R; Herrlin K. .I 275275 .U 91009406 .S J Bone Joint Surg [Br] 9101; 72(5):788-93 .M Femoral Neck Fractures/*SU; Follow-Up Studies; Hip Dislocation/ET; Hip Joint/RA; Hip Prosthesis/*/AE; Human; Pain/PP; Prospective Studies; Prosthesis Design; Prosthesis Failure; Reoperation; Support, Non-U.S. Gov't; Surgical Wound Dehiscence/ET; Surgical Wound Infection/ET. .T The Hastings bipolar hemiarthroplasty for subcapital fractures of the femoral neck. A 10-year prospective study. .P JOURNAL ARTICLE. .W In a 10-year prospective study, 561 displaced subcapital fractures of the femoral neck in 546 patients were treated with the Hastings bipolar hemiarthroplasty. Within six months of their operations, 148 patients had died. In 322 hips followed up, 243 with adequate serial radiographs separated by more than one year, only 14 (5.6%) showed acetabular erosion. A group of 91 had been reviewed for between three and nine years (mean, 4 years 10 months) and of these, 95% had no pain or slight pain only. Comparison with an earlier series of conventional hemiarthroplasties reported from this institution showed that the clinical results were similar, but that the erosion rate had been halved. .A Wetherell RG; Hinves BL. .I 275276 .U 91009407 .S J Bone Joint Surg [Br] 9101; 72(5):794-6 .M Biomechanics; Bone Nails/*; Bone Screws/*; Comparative Study; Femoral Neck Fractures/*SU; Femur Head/*SU; Fracture Fixation, Internal/*IS; Human; In Vitro; Models, Biological. .T The AO dynamic hip screw and the Pugh sliding nail in femoral head fixation. .P JOURNAL ARTICLE. .W We compared, under laboratory conditions, the resistance to cutting out of the AO dynamic hip screw and the Pugh sliding nail. The mean load at cut out, adjusted for bone strength, was 70% greater for the Pugh sliding nail. The reasons for this difference are discussed. .A Richards RH; Evans G; Egan J; Shearer JR. .I 275277 .U 91009408 .S J Bone Joint Surg [Br] 9101; 72(5):797-800 .M Aged; Aged, 80 and over; Biomechanics; Bone Screws/*; Comparative Study; Equipment Design; Female; Femoral Neck Fractures/*SU; Fracture Fixation, Internal/*IS; Human; In Vitro; Materials Testing; Models, Biological. .T Femoral neck fracture fixation. Comparison of a sliding screw with lag screws. .P JOURNAL ARTICLE. .W The rigidity of a sliding compression screw and three cannulated lag screws in the treatment of subcapital fractures was compared in five pairs of female cadaver femora. There were no significant differences between the compressive strength, bone density, cortical thickness or Singh index of the bones in each pair. A subcapital fracture was standardised using a perpendicular saw cut across the femoral neck. A uniaxial 'load test system' with force and length measurement facilities was used to mimic cyclical stressing applied in vivo at a frequency of 0.5 Hz from 0 to 3 times body-weight. There was no significant difference between the fixation afforded by the sliding compression screw and three lag screws. Bone quality was the single most important factor in the stability of the bone implant unit. .A Clark DI; Crofts CE; Saleh M. .I 275278 .U 91009409 .S J Bone Joint Surg [Br] 9101; 72(5):801-4 .M Adolescence; Adult; Aged; Aged, 80 and over; External Fixators/*; Female; Fracture Fixation/AE/*IS; Fractures, Open/*SU; Human; Male; Middle Age; Osteomyelitis/ET; Prognosis; Surgical Wound Infection/ET; Tibial Fractures/*SU. .T External fixation for type III open tibial fractures. .P JOURNAL ARTICLE. .W An analysis of 51 type III open tibial fractures treated by external skeletal fixation is presented. The fractures are subdivided according to the classification of Gustilo, Mendoza and Williams (1984) into types IIIa, IIIb and IIIc. The different prognoses of these fracture subtypes is examined. The use of the Hoffmann and Hughes external fixators in the management of type III open tibial fractures is presented and it is suggested that the prognosis is independent of the type of fixator used. .A Court-Brown CM; Wheelwright EF; Christie J; McQueen MM. .I 275279 .U 91009410 .S J Bone Joint Surg [Br] 9101; 72(5):805-9 .M Adolescence; Adult; Aged; Aged, 80 and over; Bone Nails/*; Equipment Failure; Female; Follow-Up Studies; Fracture Fixation, Intramedullary/AE/*MT; Fractures, Ununited/ET; Human; Knee Joint/PP/RA; Male; Middle Age; Prognosis; Range of Motion, Articular/PH; Tibial Fractures/PP/RA/*SU; Wound Healing/PH. .T Locked intramedullary nailing for displaced tibial shaft fractures [published erratum appears in J Bone Joint Surg [Br] 1991 Jan;73(1):181] .P JOURNAL ARTICLE. .W We analysed the results of 93 tibial shaft fractures treated with the Grosse-Kempf locked nail. Twenty-six fractures were comminuted, 19 were open grade I to II, and 54 were located outside the middle third of the tibia. The deep infection rate was 3.2%. There were only two poor results. The use of this method is recommended and discussed. .A Alho A; Ekeland A; Stromsoe K; Folleras G; Thoresen BO. .I 275280 .U 91009411 .S J Bone Joint Surg [Br] 9101; 72(5):810-5 .M Adolescence; Adult; Aged; Compartment Syndromes/ET/PC; Edema/ET/*PC/PP; Equipment and Supplies; Equipment Design; Female; Foot/*BS; Human; Leg Injuries/*CO/PP; Male; Middle Age; Pain/ET/PC; Postoperative Complications/*PC; Pressure/*; Pulsatile Flow; Support, Non-U.S. Gov't; Veins/PH. .T Reduction of post-traumatic swelling and compartment pressure by impulse compression of the foot. .P CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY. .W Following the discovery of a powerful venous pump in the foot that is activated by weight-bearing independently of muscular action, a pneumatic impulse device was developed to actuate this pump artificially. In a multicentre international trial the device was shown to reduce post-traumatic and postoperative swelling; pain also was alleviated. Evidence is also presented that dangerously high compartment pressures may be reduced to acceptable levels and fasciotomy avoided. We present an explanation of the clinical effects of activation of the venous footpump, based on recent improved understanding of the physiology of the microcirculation. The hyperaemic response that follows the liberation of endothelial-derived relaxing factor (EDRF) by sudden changes of pressure after weight-bearing or impulse compression is particularly important. .A Gardner AM; Fox RH; Lawrence C; Bunker TD; Ling RS; MacEachern AG. .I 275281 .U 91009412 .S J Bone Joint Surg [Br] 9101; 72(5):816-21 .M Adult; Aged; Biomechanics; Female; Human; In Vitro; Joint Instability/*PP; Knee Joint/*PP; Ligaments, Articular/*IN; Male; Middle Age; Models, Biological; Rotation. .T Mechanism of the pivot shift. .P JOURNAL ARTICLE. .W The mechanism of the pivot shift was investigated by analysing movements under valgus torque in 29 fresh cadaveric knees. The movements were measured in three dimensions, using biplanar photography, when all the ligaments were intact, and then after the ligaments were sequentially divided. When only the anterior cruciate ligament was sectioned, the pivot shift occurred in seven out of 20 knees examined. In the other 13, though the pivot shift was not observed, an abnormal internal rotation occurred at between 10 degrees and 50 degrees of flexion. Division of the iliotibial tract in addition to division of the anterior cruciate ligament stopped the pivot shift, as the tibia remained internally rotated throughout the range of flexion. The axis of rotation of the pivot shift was located at the medial collateral ligament, which was kept tight by the applied valgus torque. The sudden movement in the pivot shift was caused by a complex interaction between the geometry of the knee and the valgus torque applied. .A Matsumoto H. .I 275282 .U 91009413 .S J Bone Joint Surg [Br] 9101; 72(5):822-9 .M Animal; Fractures/PA/*PP; Hematoma/PA/*PP; Male; Muscles/SU; Osteogenesis/*PH; Periosteum/SU; Rats; Rats, Inbred Strains; Tissue Transplantation; Wound Healing/PH. .T The osteogenetic potential of fracture haematoma. Subperiosteal and intramuscular transplantation of the haematoma. .P JOURNAL ARTICLE. .W We studied the precise role of the fracture haematoma in healing by the experimental transplantation of the haematoma at two days and four days after fracture of the rat femur to subperiosteal and intramuscular sites. We used bone marrow and peripheral blood haematomas for control experiments. The transplanted two-day fracture haematoma produced new bone by endochondral ossification at the subperiosteal site, but not at the intramuscular site. Four-day fracture haematoma produced new bone formation at both subperiosteal and intramuscular sites. These results suggest that fracture haematoma has an inherent osteogenetic potential. .A Mizuno K; Mineo K; Tachibana T; Sumi M; Matsubara T; Hirohata K. .I 275283 .U 91009414 .S J Bone Joint Surg [Br] 9101; 72(5):830-4 .M Animal; Bone Resorption/PP; Bone Transplantation/*PH; Callus/PH; Cats; Tibia/BS/TR; Wound Healing/PH. .T Healing of non-vascularised diaphyseal bone transplants. An experimental study. .P JOURNAL ARTICLE. .W Four different experiments were performed to study the healing of a large, non-vascularised, diaphyseal, bone segment in adult cats. In the first experiment, a 4 cm segment of tibia with its periosteum was excised and replaced in its bed. The other experiments were similar, except that in the second, the periosteum of the segment was removed, in the third its medullary canal was blocked with a Silastic rod, and in the last group the segment was isolated from its muscle bed by a Silastic sheet. The reparative processes were quantified by estimating the resorption index, the cortical new bone formation index, the callus encasement index, and the osteocyte count. Bone resorption and apposition occurred in the segment even when the periosteum was absent or the medullary canal was blocked, with osseous union at both ends by eight to 12 weeks, provided the segment was not isolated from its muscle bed. Thus, the muscle bed played a significant role in these reparative processes. .A Nather A; Balasubramaniam P; Bose K. .I 275284 .U 91009415 .S J Bone Joint Surg [Br] 9101; 72(5):835-8 .M Adult; Bone Screws/*; Bone Transplantation/*MT; Carpal Bones/*IN/RA; Female; Fracture Fixation, Internal/*IS; Fractures, Ununited/RA/*SU; Human; Male; Middle Age; Retrospective Studies. .T Corticocancellous grafting and an AO/ASIF lag screw for nonunion of the scaphoid. A retrospective analysis. .P JOURNAL ARTICLE. .W We report our experience in 42 patients, using corticocancellous bone grafts and lag screw fixation for un-united scaphoid fractures. Using a grading system, we analysed the suitability of the method for three types of nonunion. We recommend the operation for the treatment of scaphoid nonunion, except where there is avascular necrosis of the proximal pole. .A Sukul DM; Johannes EJ; Marti RK. .I 275285 .U 91009416 .S J Bone Joint Surg [Br] 9101; 72(5):839-42 .M Aged; Aged, 80 and over; Arthrodesis/*/AE; Arthroplasty/*/AE; Comparative Study; Consumer Satisfaction; Female; Hallux Valgus/PP/*SU; Human; Male; Metatarsophalangeal Joint/*SU; Middle Age; Pain/PP; Prospective Studies; Range of Motion, Articular/PH; Reoperation; Support, Non-U.S. Gov't. .T The management of the painful first metatarsophalangeal joint in the older patient. Arthrodesis or Keller's arthroplasty? .P CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL. .W We report a prospective randomised trial comparing Keller's arthroplasty and arthrodesis of the first metatarsophalangeal joint for the management of symptomatic hallux valgus and hallux rigidus in the older patient. In 81 patients (110 feet), with a minimum of two years follow-up, both procedures gave a similar degree of patient satisfaction and symptom relief. The incidence of metatarsalgia was also similar. As there were no obvious advantages to arthrodesis, and since six out of 50 arthrodesed toes required revision, we suggest that Keller's arthroplasty is the better operation in these patients. .A O'Doherty DP; Lowrie IG; Magnussen PA; Gregg PJ. .I 275286 .U 91009417 .S J Bone Joint Surg [Br] 9101; 72(5):843-5 .M Biomechanics; Human; Humerus/PH; In Vitro; Movement/PH; Posture; Reference Values; Rotation; Scapula/PH; Shoulder Joint/*PH; Support, Non-U.S. Gov't. .T Glenohumeral elevation studied in three dimensions. .P JOURNAL ARTICLE. .W We studied the position and rotational changes associated with elevation of the glenohumeral joint, using a three-dimensional magnetic-field tracking system on nine fresh cadaveric shoulders. The plane of maximal arm elevation was shown to occur 23 degrees anterior to the plane of the scapula. Elevation in any plane anterior to the scapula required external humeral rotation, and maximal elevation was associated with approximately 35 degrees of external humeral rotation. Conversely, internal rotation was necessary for increased elevation posterior to the plane of the scapula. The observed effects of this rotation were to clear the humeral tuberosity from abutting beneath the acromion and to relax the inferior capsular ligamentous constraints. Measurement of the obligatory humeral rotation required for maximal elevation helps to explain the relationship of the limited elevation seen in adhesive capsulitis and after operations which limit external rotation. .A Browne AO; Hoffmeyer P; Tanaka S; An KN; Morrey BF. .I 275287 .U 91009418 .S J Bone Joint Surg [Br] 9101; 72(5):846-51 .M Antibiotics/TU; Arthritis, Infectious/RA; Combined Modality Therapy; Follow-Up Studies; Hip Joint/RA; Human; Infant, Newborn; Osteomyelitis/*RA/TH; Prognosis; Retrospective Studies; Staphylococcal Infections/DT; Streptococcal Infections/DT; Support, Non-U.S. Gov't. .T Neonatal osteomyelitis. .P JOURNAL ARTICLE. .W Thirty-four neonates with osteomyelitis were reviewed. The hip (19) was the most common site involved. Swelling and pseudoparalysis were the most significant local signs. Radiographic abnormalities, such as metaphyseal rarefaction and/or joint subluxation were found on the initial radiographs in 18 of the 19 hips involved. All patients were treated with antibiotics and all infections involving joints were drained surgically. Good results were achieved in 75% of all sites and in 68% of hips. .A Knudsen CJ; Hoffman EB. .I 275288 .U 91009419 .S J Bone Joint Surg [Br] 9101; 72(5):852-3 .M Acute Disease; Child; Child, Preschool; Follow-Up Studies; Hip Joint/*US; Human; Suction/*MT; Synovitis/*US. .T Ultrasound-guided aspiration for transient synovitis of the hip. .P JOURNAL ARTICLE. .W We reviewed 15 children with transient synovitis of the hip who had aspiration of an effusion under local anaesthesia with ultrasound guidance. There were no significant complications; aspiration was useful for diagnosis and gave considerable symptomatic relief. We discuss the role of ultrasound in diagnosis and treatment. .A Hill SA; MacLarnon JC; Nag D. .I 275289 .U 91009420 .S J Bone Joint Surg [Br] 9101; 72(5):854-8 .M Adolescence; Child; Epiphyses, Slipped/PP/RA/*SU; Female; Femur/*SU; Femur Head Necrosis/ET; Follow-Up Studies; Hip Joint/PP/RA; Human; Male; Movement/PH; Postoperative Complications; Rotation; Tomography, X-Ray Computed. .T Surgical treatment for severe slipping of the upper femoral epiphysis. .P JOURNAL ARTICLE. .W We have used a modified technique of cervical osteotomy to treat a consecutive series of 23 patients with chronic slip of the upper femoral epiphysis. It has been successful in correcting both moderate and severe deformities with a low incidence of avascular necrosis, comparable to that seen after subtrochanteric osteotomies. We describe the operative details and discuss the features which make cervical osteotomy technically superior to intertrochanteric and subtrochanteric procedures. .A Clarke HJ; Wilkinson JA. .I 275290 .U 91009421 .S J Bone Joint Surg [Br] 9101; 72(5):859-61 .M Adolescence; Adult; Aging/PH; Bone Regeneration/PH; Child; Child, Preschool; Elbow Joint/PP/RA/*SU; Female; Follow-Up Studies; Human; Male; Osteotomy/*AE; Range of Motion, Articular/PH. .T The lateral condylar prominence. A complication of supracondylar osteotomy for cubitus varus. .P JOURNAL ARTICLE. .W We reviewed 27 patients who had supracondylar closing wedge osteotomy for cubitus varus. There were 10 excellent and 12 good results. However, of these 22 patients, 14 had a significant bony prominence over the lateral condylar region caused by lateral displacement of the elbow when closing the osteotomy. This prominence was less obvious in patients who had their osteotomy at a young age, but worse after operations near or after skeletal maturity. This difference appeared to be due to remodelling. .A Wong HK; Lee EH; Balasubramaniam P. .I 275291 .U 91009422 .S J Bone Joint Surg [Br] 9101; 72(5):862-5 .M Adipose Tissue/*RA; Bone Cysts/*RA; Bone Density/PH; Case Report; Child; Diagnosis, Differential; Female; Hematoma/PP/RA; Human; Male; Osteogenesis/PH; Radius Fractures/*RA; Tomography, X-Ray Computed. .T Transient cyst-like cortical defects following fractures in children. Medullary fat within the subperiosteal haematoma. .P JOURNAL ARTICLE. .W Asymptomatic cyst-like cortical defects appearing after fractures in children have been occasionally reported. Typically, these defects appear during fracture consolidation, within the newly formed subperiosteal bone, proximal to the fracture line, do not enlarge, and progressively disappear. We have previously shown a fatty density on CT scan within the early cortical defect. We now present two additional cases in which early CT scans appeared to confirm that these transient cortical defects may consist of fat, and probably result from the inclusion of medullary fat within the subperiosteal haematoma. .A Malghem J; Maldague B; Claus D; Clapuyt P. .I 275292 .U 91009423 .S J Bone Joint Surg [Br] 9101; 72(5):866-73 .M Adolescence; Adult; Aged; Cartilage, Articular/*AH; Collagen/UL; Femur/AH; Human; Humerus/AH; Microscopy, Electron, Scanning; Middle Age; Osteocytes/UL; Reference Values; Support, Non-U.S. Gov't; Tibia/AH. .T The structure of the human subchondral plate. .P JOURNAL ARTICLE. .W To study the anatomy of subarticular bone and cartilage, fresh specimens of cartilage on bone from the human shoulder, hip and knee were treated with bleach or papain, or were fixed and decalcified. All were compared using scanning electron microscopy. Papain digestion selectively removed cartilage to the tidemark. The tidemark contour was highly variable; irregularities were indirectly related to degenerative lesions and were most prominent in peripheral non-weight-bearing areas of joints with central fibrillation. Decalcification exposed the interface between the bone and calcified cartilage. Collagen fibrils in articular cartilage did not interdigitate with those of bone. The subchondral bone was appositional, avascular, smooth and very thin in most areas of human joints. Perforations through subchondral bone or calcified cartilage were rare. Bleach maceration destroyed important details. .A Clark JM; Huber JD. .I 275293 .U 91009424 .S J Bone Joint Surg [Br] 9101; 72(5):874-80 .M Animal; Collagen/UL; Female; Freeze Drying; Guinea Pigs; Leprosy, Tuberculoid/CO/PA/*SU; Muscles/IR/*TR; Nerve Regeneration/*PH; Peripheral Nerve Diseases/ET/*SU; Schwann Cells/UL; Support, Non-U.S. Gov't; Tibial Nerve/PH/SU/UL. .T Denatured muscle grafts for nerve repair. An experimental model of nerve damage in leprosy [see comments] .P JOURNAL ARTICLE. .W About 20% of patients with leprosy develop localised granulomatous lesions in peripheral nerves. We report experiments in guinea-pigs in which freeze-thawed autogenous muscle grafts were used for the treatment of such mycobacterial granulomas. Granulomas were induced in guinea-pig tibial nerves and the animals were left for 7 to 100 days in order to assess maximal damage. The local area of nerve damage was then excised and the gap filled with denatured muscle grafts. Clinical assessment after periods up to 150 days showed good sensory and motor recovery which correlated well with the histological findings. The muscle graft technique may be of value for the treatment of chronic nerve lesions in selected cases of leprosy. .A Pereira JH; Cowley SA; Gschmeissner SE; Bowden RE; Turk JL. .I 275294 .U 91009425 .S J Bone Joint Surg [Br] 9101; 72(5):881-3 .M Adult; Aged; Female; Follow-Up Studies; Human; Male; Metacarpophalangeal Joint/PP/*SU; Middle Age; Range of Motion, Articular/PH; Rupture; Tendon Injuries/PP/*SU; Tendon Transfer/*; Thumb/*/PP. .T Extensor indicis proprius transfer for rupture of the extensor pollicis longus tendon. .P JOURNAL ARTICLE. .W We reviewed 21 patients with 22 ruptures of the extensor pollicis longus at a mean of 5.3 years after transfer of the extensor indicis proprius tendon. Of these, 19 with 21 transfers described the result as good, and two as fair. The mean deficit of extension between the operated and unoperated thumbs was 1.4 cm, and the mean flexion deficit 0.6 cm. Pressure gauge measurements showed that the strength of the transfer was 51% of that of the uninjured extensor. The two fair results had an extensor lag of over 1.5 cm. Independent extension of the index was maintained in all patients, none having a discernible lag, but the strength of index extension was reduced to 49% of that of the normal finger. There was no evidence of functional loss. Extensor indicis proprius transfer for rupture of the extensor pollicis longus tendon is a simple and reliable procedure with few complications. It gives satisfactory long-term extension of the thumb. .A Magnussen PA; Harvey FJ; Tonkin MA. .I 275295 .U 91009426 .S J Bone Joint Surg [Br] 9101; 72(5):884-5 .M Adult; Biopsy/MT; Bone Cysts/*PA/RA; Case Report; Human; Male; Spinal Diseases/PA; Thoracic Vertebrae/*PA; Tomography, X-Ray Computed. .T Open transpedicular biopsy of the vertebral body. .P JOURNAL ARTICLE. .W We describe a method of obtaining a biopsy from the body of a vertebra by an open transpedicular route. This minimises the danger of contamination of tissue planes and spaces. .A Fidler MW; Niers BB. .I 275296 .U 91009427 .S J Bone Joint Surg [Br] 9101; 72(5):886-8 .M Equipment Design; Human; Implants, Artificial/*; Lumbar Vertebrae/RA/*SU; Radiation Dosage; Surgical Instruments/*; Thoracic Vertebrae/RA/*SU. .T A target device for placement of implants in the thoracolumbar pedicles. .P JOURNAL ARTICLE. .W Posterior spinal instrumentation with the placement of intrapedicular implants has become an important technique. We have designed a hand-held target device to facilitate the open or percutaneous location and penetration of the thoracolumbar pedicles. A cylindrical pin guide incorporates two metal rings and can be moved under image intensifier control until the rings are superimposed to show correct alignment. The radiation dosage for the surgeon is minimal; the device allowed accurate placement of 106 consecutive pedicle screws. .A Pennig D; Brug E. .I 275297 .U 91009428 .S J Bone Joint Surg [Br] 9101; 72(5):889-93 .M Animal; Biocompatible Materials/*; Ceramics/*; Implants, Artificial/*; Lumbar Vertebrae/*SU; Male; Materials Testing; Sheep. .T Replacement of the lumbar vertebrae of sheep with ceramic prostheses. .P JOURNAL ARTICLE. .W We prepared a prosthesis for the replacement of the lumbar vertebrae of sheep, using apatite- and wollastonite-containing glass-ceramic. The material is stronger than human cortical bone and has the special feature of chemical bonding to bone. Ten sheep underwent replacement of L3 and L4 vertebrae, without bone grafting. The animals were killed at intervals from three months to 27 months after operation, and the interface between the prosthesis and bone was examined radiologically, histologically and crystallographically. Bone bonding with the prosthesis had occurred in half the implants. It took at least one year for bonding to be complete, but an apatite layer on the surface of the prosthesis was observed as early as three months after the operation, suggesting the possibility of much earlier bone bonding if more rigid fixation of the prosthesis had been provided. .A Yamamuro T; Shikata J; Okumura H; Kitsugi T; Kakutani Y; Matsui T; Kokubo T. .I 275298 .U 91009429 .S J Bone Joint Surg [Br] 9101; 72(5):894-900 .M Adolescence; Adult; Child; Consumer Satisfaction; Follow-Up Studies; Human; Neuralgia/ET; Postoperative Complications; Reoperation; Respiratory Function Tests; Ribs/*SU; Scoliosis/PX/RA/*SU; Surgical Wound Infection/ET. .T The modified Schollner costoplasty. .P JOURNAL ARTICLE. .W The modified Schollner costoplasty is a cosmetic procedure for the correction of rib prominence deformity in scoliosis. We present the results of the procedure in 21 patients who had previously undergone spinal fusion for scoliosis. We found the procedure to be well tolerated without major complications. Objective cosmetic improvement was achieved in all but one case. All but one patient considered the procedure to have been of cosmetic benefit. .A Broome G; Simpson AH; Catalan J; Jefferson RJ; Houghton GR. .I 275299 .U 91009430 .S J Bone Joint Surg [Br] 9101; 72(5):901-3 .M Adult; Aged; Female; Follow-Up Studies; Human; Jurisprudence; Male; Middle Age; Movement/PH; Neck/*IN/PP; Prognosis; Whiplash Injuries/EC/*PP. .T Long-term prognosis of soft-tissue injuries of the neck. .P JOURNAL ARTICLE. .W We reviewed 43 patients who had sustained soft-tissue injuries of the neck after a mean 10.8 years. Of these, only 12% had recovered completely. Residual symptoms were intrusive in 28% and severe in 12%. Pain in the neck and lower back was the commonest complaint and older patients had a worse prognosis. After two years, symptoms did not alter with further passage of time. .A Gargan MF; Bannister GC. .I 275300 .U 91009431 .S J Bone Joint Surg [Br] 9101; 72(5):904-7 .M Adult; Aged; Brachial Plexus/SU; Cervical Vertebrae/*SU; Chronic Disease; Female; Human; Male; Middle Age; Neuritis/SU; Osteomyelitis/SU; Postoperative Complications; Spinal Cord Diseases/SU; Spinal Diseases/SU; Spinal Neoplasms/SU; Surgical Flaps; Thoracic Vertebrae/*SU. .T A surgical approach to the cervicothoracic spine. .P JOURNAL ARTICLE. .W We describe a method for approaching the lower cervical and upper thoracic spine, the brachial plexus and related vessels. The method involves the elevation of the medial corner of the manubrium, the sternoclavicular joint, and the medial half of the clavicle on a pedicle of the sternomastoid muscle. We have used this exposure in 17 cases with few complications and good results. Its successful performance requires high standards of anaesthesia, surgical technique and postoperative care. .A Birch R; Bonney G; Marshall RW. .I 275301 .U 91009432 .S J Bone Joint Surg [Br] 9101; 72(5):908-13 .M Adolescence; Child; Comparative Study; Female; Follow-Up Studies; Human; Length of Stay; Male; Pain/PP; Postoperative Complications; Reoperation; Retrospective Studies; Spinal Fusion; Spondylolisthesis/RA/SU/*TH. .T Operative and conservative treatment of moderate spondylolisthesis in young patients. .P JOURNAL ARTICLE. .W We made a retrospective study of 149 children and adolescents with moderate spondylolisthesis (slip less than or equal to 30%), 77 treated by fusion and 72 conservatively at an average follow-up of 13.3 years. Both groups were fully comparable with regard to age at diagnosis, sex distribution (46% girls), and mean slip. The patients who were treated operatively had more pain before treatment and showed more initial progression of the slip. They had better clinical results and less pain at latest review, but the total progression of the slip over the whole follow-up showed no statistical differences between the two groups. Patients with a pseudarthrosis after attempted fusion had had a longer period of postoperative pain, but at the latest review had no more pain than those with sound fusion. None of those treated conservatively came to fusion later and the long-term results in 18 patients who had refused the advised operation were no worse than those for other conservatively treated patients. Our results suggest that a moderate grade of spondylolisthesis in adolescents usually has a benign course. It seems that spontaneous segmental stabilisation occurs as a result of degeneration of the disc at the level of the slip. .A Seitsalo S. .I 275302 .U 91009433 .S J Bone Joint Surg [Br] 9101; 72(5):914-6 .M Adolescence; Case Report; Diseases in Twins/*GE; Female; Human; Intervertebral Disk Displacement/*GE/RA; Lumbar Vertebrae/*RA; Support, Non-U.S. Gov't; Tomography, X-Ray Computed; Twins, Monozygotic. .T Lumbar intervertebral disc prolapse in teenage twins. A case report and review of the literature. .P JOURNAL ARTICLE; REVIEW; REVIEW OF REPORTED CASES. .W We report the cases of teenage twin girls presenting within months of each other with severe symptoms from lumbosacral disc prolapses, requiring laminectomy in one and chemonucleolysis in the other. CT scans showed similarities in spinal configuration, including the presence of disc bulges at the L4-5 level. This suggests a strong hereditary factor in prolapse of intervertebral discs, but a review of the literature showed little information on that aspect. .A Gunzburg R; Fraser RD; Fraser GA. .I 275303 .U 91009434 .S J Bone Joint Surg [Br] 9101; 72(5):917-20 .M Adolescence; Adult; Aged; Backache/EP/ET; Female; Human; Incidence; Intervertebral Disk Displacement/CO/*RA; Lumbar Vertebrae/*RA; Male; Middle Age; Pilot Projects. .T Radiographic appearances in lumbar disc prolapse. .P JOURNAL ARTICLE. .W The pre-operative lumbar spine radiographs of 200 consecutive patients who had undergone discectomy for prolapsed intervertebral disc were reviewed. Prolapse was recognized as bulging or sequestration of the disc with consequent root compromise. Measurement of the lumbar level of the interiliac line was shown to correlate with the level of disc prolapse and the incidence of transitional vertebrae at the lumbosacral junction was significantly higher than normal. A pathological value for the lumbosacral angle could not be identified. .A MacLean JG; Tucker JK; Latham JB. .I 275304 .U 91009435 .S J Bone Joint Surg [Br] 9101; 72(5):921 .M Adult; Female; Follow-Up Studies; Hallux Valgus/*SU; Human; Osteotomy/*MT; Recurrence; Rotation. .T Cuneiform rotation osteotomy for relapsed hallux valgus. .P JOURNAL ARTICLE. .A Kemp HB. .I 275305 .U 91009436 .S J Bone Joint Surg [Br] 9101; 72(5):922 .M Bone Nails; Femoral Fractures/*RA/SU; Fracture Fixation, Internal/*MT; Human; Radiation Dosage; Radiation Protection/*MT; X-Ray Intensifying Screens. .T A lead apron for closed femoral nailing. .P JOURNAL ARTICLE. .A Mahaisavariya B; Suibnugarn C; Laupattarakasem W; Kowsuwon W. .I 275306 .U 91009437 .S J Bone Joint Surg [Br] 9101; 72(5):923 .M Adolescence; Aneurysm/*CO; Case Report; Compartment Syndromes/*ET; Forearm/*BS; Forearm Injuries/*CO; Human; Male; Wounds, Penetrating/*CO. .T Compartment syndrome caused by false aneurysm. .P JOURNAL ARTICLE. .A Savage R. .I 275307 .U 91009439 .S J Bone Joint Surg [Br] 9101; 72(5):925 .M Brain Neoplasms/CO/*DI; Case Report; Human; Male; Meningeal Neoplasms/CO/*DI; Meningioma/CO/*DI; Middle Age; Seizures/CO/ET; Shoulder Dislocation/*ET/RA; Shoulder Fractures/*ET/RA; Tomography, X-Ray Computed. .T Brain tumour presenting as a dislocated shoulder. .P JOURNAL ARTICLE. .A Elliott DS. .I 275308 .U 91009440 .S J Bone Joint Surg [Br] 9101; 72(5):926 .M Bone Nails/*; Fracture Fixation, Intramedullary/*MT; Human; Posture; Tibial Fractures/RA/*SU. .T Closed intramedullary nailing of the tibia. .P JOURNAL ARTICLE. .A Bamford D; Stanley D. .I 275309 .U 91009441 .S J Bone Joint Surg [Br] 9101; 72(5):927 .M Aged; Arthrography; Bursa, Synovial/*RA; Case Report; Diagnosis, Differential; Female; Human; Joint Diseases/DI; Popliteal Cyst/*RA; Rupture, Spontaneous/DI; Thrombophlebitis/*DI. .T Spontaneous rupture of the suprapatellar bursa. .P JOURNAL ARTICLE. .A McCabe JP; Gilmore MF. .I 275310 .U 91009442 .S J Bone Joint Surg [Br] 9101; 72(5):928-9 .M Adolescence; Case Report; Diseases in Twins/*GE; Epiphyses, Slipped/*GE/PP/RA/SU; Femur/SU; Hip Joint/PP/RA; Human; Male; Twins, Monozygotic. .T Simultaneous slipped upper femoral epiphysis in identical twins. .P JOURNAL ARTICLE. .A Allen CP; Calvert PT. .I 275311 .U 91009443 .S J Bone Joint Surg [Br] 9101; 72(5):929 .M Adolescence; Arthroscopy/*AE/MT; Case Report; Embolism, Air/*ET; Female; Human; Insufflation/*AE; Knee Injuries/CO/*DI; Tibial Fractures/*CO. .T Fatal air embolism during arthroscopy. .P JOURNAL ARTICLE. .A Gruenwald JM. .I 275312 .U 91009444 .S J Cardiovasc Surg (Torino) 9101; 31(4):413-5 .M Angiography; Angioplasty, Transluminal/*MT; Atherosclerosis/RA/*TH; Femoral Artery; Human; Lasers/AE/*TU; Popliteal Artery; Support, Non-U.S. Gov't; Vascular Patency. .T Initial experience with the "Smart" laser in the treatment of atherosclerotic occlusions. .P JOURNAL ARTICLE. .W A dual laser system capable of distinguishing atherosclerotic plaque from components of normal arterial wall was used to deliver laser energy to cut a channel through occluded vessels. This system was used to facilitate balloon angioplasty of short (3-17 cm) total occlusions of the superficial femoral or popliteal arteries in 17 patients. In 10 patients the occluding lesion was traversed by the laser wire and patency was effectively restored by balloon angioplasty. Satisfactory luminal patency has persisted for 2 to 12 months (mean 6 months) in 9 cases; the lesion in the tenth patient restenosed at 3 months. The laser procedure was unsuccessful in all 3 cases with occlusions over 10 cm and in 4 others. There were no clinically important complications. This experience suggests that most patients who presently require interventional treatment can be managed by standard angioplasty methods and/or require a bypass operation. The "Smart" laser is safe and effective short-term in facilitating angioplasty in some patients in whom standard angioplasty techniques are not feasible. The implications of these findings are discussed. .A Veith FJ; Bakal CW; Cynamon JA; Gupta SK; Keeley J; Greenberg M; Mennigus MA; Ascer E; Dietzek AM; Wengerter KR. .I 275313 .U 91009445 .S J Cardiovasc Surg (Torino) 9101; 31(4):416-23 .M Adult; Aged; Aged, 80 and over; Female; Femoral Vein/*SU; Human; Ligation/MO/MT; Male; Middle Age; Phlebography; Plethysmography; Popliteal Vein; Prognosis; Pulmonary Embolism/*PC; Recurrence; Survival Rate; Thrombophlebitis/RA/*SU. .T Ligation of the superficial femoral vein in prevention of pulmonary embolism: an old fashion procedure? .P JOURNAL ARTICLE. .W From 1974 to 1988, interruption of the superficial femoral vein (SFV) was performed to prevent pulmonary embolism (PE) in 73 patients. The mean age of the patients was 62 years. Phlebography showed thrombi in the following localizations: calf veins (67.3%), superficial femoral or popliteal veins (56.6%), common femoral veins (19.5%) and iliac veins (2.7%). A floating thrombus in the popliteal or femoral vein was the main indication for surgery in 97.3% of patients. Pulmonary embolism had occurred in 76.7% and was associated with neoplasm in 13.7%. Ligation of the SFV was performed in 93 limbs and completed iliac or femoral thrombectomy in 32.3%. The procedure was performed under locoregional anesthesia in 82.9% of the cases. Hospital mortality was 1.4% and 3 year survival, considering only PE related deaths was 95.3 +/- 2.7%. Follow-up was complete for all patients and averaged 3.0 years, for a 3 years PE-free rate of 90.8 +/- 3.6%. Persistent symptoms included increased limb tenseness in 12.5% and mild ankle edema in 25%. Bilateral strain-gauge plethysmography (SGP) was obtained in 65 limbs. The time necessary to obtain a 50, 75 and 100% decrease in calf volume (respectively T1/2, T3/4 and TT) was calculated for the operated limb and compared with the untreated limbs used as controls. A prolongation of T1/2 from 2.5 +/- 0.3 sec in controls to 4.3 +/- 0.4 sec in the operated limb (p less than 0.01) was found. Thus, our experience with ligation of the superficial femoral vein is favourable since long-term ill effects have been minimal and strain gauge plethysmography (SGP) showed only mildly altered venous drainage.(ABSTRACT TRUNCATED AT 250 WORDS) .A Louagie Y; Van Ruyssevelt P; el Hammouti F; Theys S; Janssens T; Buche M; Schoevaerdts JC. .I 275314 .U 91009446 .S J Cardiovasc Surg (Torino) 9101; 31(4):424-9 .M Aged; Angiography; Arteriovenous Shunt, Surgical/*MT; Carotid Arteries/PA/RA/*SU; Carotid Artery, Internal/PA; Constriction, Pathologic/ET; Endarterectomy/AE/MO/*MT; Female; Human; Intraoperative Period; Male; Middle Age; Recurrence; Thrombosis/ET/MO. .T The relationship of intraluminal shunting to technical results after carotid endarterectomy. .P JOURNAL ARTICLE. .W This study evaluates the incidence of defects on the intraoperative angiograms of 160 carotid endarterectomies performed in 146 patients, 81 of 160 (50.6%) with a shunt and 79 of 160 operations (49.4%) performed without a shunt. Angiographic defects were identified in 34 of 160 carotid endarterectomies (21%), of which 21 of 34 (65%) resulted in a greater than 20% stenosis of the internal carotid artery (ICA). There were defects in 6 of 81 (7.4%) shunted vessels compared to 16 of 79 (20%) of those not shunted (p less than 0.05). Thirty-one vessels were reexplored 11 of 81 (13.5%) of those shunted and 20 of 79 (20%) of those not shunted (p less than 0.05). There were four strokes (2.5%) (2 in each group) and one death due to myocardial infarction (0.6%) in the postoperative period. Duplex follow-up from 1-60 months (median 22 months) was available in 114 of 160 (71%) endarterectomies. A stenosis of greater than 50% was detected in 7 of 114 (6%) carotid arteries; 5 of the 7 (71%) were shunted and 2 (29%) were nonshunted. Unrepaired defects were present in 3 of 7 (43%) and no defects in the remaining 4 of 7 (57%) arteries. We conclude that the use of a shunt significantly decreases the number of ICA defects detected angiographically and that immediate revision of demonstrable defects can be undertaken with low morbidity and does not predispose the patient to recurrent stenosis. .A Strawn DJ; Hunter GC; Guernsey JM; Kishore C. .I 275315 .U 91009447 .S J Cardiovasc Surg (Torino) 9101; 31(4):430-7 .M Adult; Aged; Aorta, Thoracic/*SU; Blood Vessel Prosthesis; Female; Femoral Artery/*SU; Graft Occlusion, Vascular/CO/SU; Human; Iliac Artery/SU; Ischemia/ET; Male; Methods; Middle Age; Postoperative Complications/MO; Prospective Studies; Prosthesis Failure; Reoperation; Retroperitoneal Space. .T Long term follow-up of descending thoracic aorto-iliac/femoral bypass. .P JOURNAL ARTICLE. .W A prospective study of 26 patients undergoing descending thoracic aorto-iliac/femoral (DTAI/F) bypass was conducted over a 13-year period with an average follow up of 53 months. Reasons for selecting the procedure were occluded aortic bifurcation grafts (9 patients), hostile abdomen (6), infected aortic graft (1), microaorta (10, and surgeons preference in 8 patients who had juxtarenal aortic occlusion. The operative mortality was 3.8% (1 patient). A late mortality of 36% was due to myocardial infarction (1), lung carcinoma (2), renal failure (4), stroke (1) and pulmonary insufficiency (1). Graft failure occurred in 4 patients at 23, 26, 54 and 109 months respectively. Primary cumulative patency was 86% statistically valid at 42 months. DTAI/F bypass is recommended in selected patients when conventional approaches to the aorta are considered unduly hazardous. .A Bowes DE; Youkey JR; Pharr WP; Goldstein AM; Benoit CH. .I 275316 .U 91009448 .S J Cardiovasc Surg (Torino) 9101; 31(4):438-41 .M Aged; Aged, 80 and over; Aorta/*SU; Aorta, Abdominal; Aortic Aneurysm/CO/*SU; Arterial Occlusive Diseases/CO/*SU; Comparative Study; Female; Femoral Artery/SU; Human; Male; Middle Age; Mortality; Risk Factors. .T Current results of elective aortic reconstruction for aneurysmal and occlusive disease. .P JOURNAL ARTICLE. .W Decisions to resect small aortic aneurysms or employ non-operative treatment for aorto-iliac occlusive disease must depend on current rather than historical surgical results. To assess current morbidity and mortality, we reviewed 200 consecutive aortic resections in two groups of patients treated from 1981 to 1989: those undergoing elective aortofemoral bypass for occlusive disease (AFB, no. 100) or resection of infrarenal abdominal aortic aneurysms (AAA, no. 100). Indications for AFB included claudication (54%), rest pain (32%), and gangrene (13%). AAA size ranged from 3 to 14 cm (mean 6.5 +/- 2.4 cm); 45% presented with abdominal or back pain. Patients undergoing AFB were younger (AFB 61.5 +/- 10 years vs AAA 68.7 +/- 8.9 years) with a higher incidence of some atherosclerotic risk factors, diabetes mellitus 30% vs 10%, tobacco use 77% vs 49%, hyperlipidemia 21% vs 7%; p less than 0.001). Coronary artery disease (CAD) was more prevalent in AAA patients (49% vs 34%; p less than 0.001). Postoperative mortality was not different in occlusive or aneurysmal disease (3% AFB vs 2% AAA), nor was the occurrence of serious complications such as myocardial infarction (2% vs 1%) or pulmonary embolism (2% vs 3%). Improvements in patient selection, perioperative care and surgical technique have lowered the mortality of elective aortic surgery. Given the current standard of care, an aggressive approach to AAA even in high risk patients is appropriate. The low morbidity of AFB for occlusive disease mandates a critical appraisal of less effective nonoperative therapies. .A Clark ET; Gewertz BL; Bassiouny HS; Zarins CK. .I 275317 .U 91009449 .S J Cardiovasc Surg (Torino) 9101; 31(4):442-7 .M Aged; Anesthesia, Epidural/*; Anesthesia, General/*; Aortic Aneurysm/SU; Aortic Diseases/*SU; Arterial Occlusive Diseases/SU; Comparative Study; Hemodynamics/DE; Human; Injections, Epidural; Morphine/AD; Pain/DT; Postoperative Complications/MO. .T Combined epidural and general anesthesia in aortic surgery. .P JOURNAL ARTICLE. .W The perioperative course of 144 consecutive patients undergoing aortic reconstructive surgery was studied to assess the potential benefit of employing a combined epidural and light general anesthesia technique. A group of 67 patients had general anesthesia alone (GA), while in the group of 77 remaining patients, a combined epidural and general anesthesia (Epi-GA) was employed. The two groups were similar in regards to age, medical risk factors, preoperative assessment of cardiac and pulmonary function, and type of surgical reconstruction. There was no significant difference in the anesthetic, operative time, or operative fluid requirements between the two groups. There was a lower rate pressure product in the Epi-GA group during aortic cross clamping (P less than 0.05). More patients in the GA group required a prolonged ventilatory support (P less than 0.05) and a high parenteral narcotic administration (P less than 0.025) during the first 48 hours. While the mortality rate was similar for the two groups (3.0% for GA group vs 5.2% for Epi-GA group), there was a higher percent of postoperative pulmonary complications observed in the GA group (7.6%) compared to the Epi-GA group (2.6%). By facilitating early extubation and a decreased need for systemic narcotics in the early postoperative period, Epi-GA may be beneficial in the high risk pulmonary patient undergoing aortic reconstruction. .A Mason RA; Newton GB; Cassel W; Maneksha F; Giron F. .I 275318 .U 91009450 .S J Cardiovasc Surg (Torino) 9101; 31(4):448-52 .M Aged; Aorta/SU; Arterial Occlusive Diseases/*SU; Female; Femoral Artery/SU; Human; Iliac Artery/SU; Ischemia/SU; Leg/BS; Male; Middle Age; Popliteal Artery/SU; Retrospective Studies; Survival Rate; Vascular Patency; Vascular Surgery/*MT. .T Synchronous reconstruction for combined aortoiliac and femoropopliteal occlusive lesions. The role of proximal bypass. .P JOURNAL ARTICLE. .W Between January 1984 and December 1986, 31 patients underwent synchronous revascularization (SR) because of the serious clinical condition of a lower limb and presence of arteriographically visible lesions. Average follow-up was 30 months. Operative mortality was 10%. Two patient populations were identified: Group I (N = 13): patients who underwent ilio-femoral or aorto-femoral proximal revascularization (PR); Group II (N = 18): patients who had axillo-femoral PR. Group I patients were younger than those in Group II (64 yr versus 72 yr; p less than 0.01). An association of pre-operative risk factors (arterial hypertension; coronary, renal or respiratory insufficiency) was twice as frequent in Group II as in Group I (p less than 0.02). The rate of SR compared to PR alone was 15%. However, there was no statistically significant difference between Groups I and II. Comparison of the actuarial survival curves for patients ahd the patency rates of SR in Groups I and II failed to reveal any statistically significant differences. Axillo-femoral bypass can be used for PR when SR is necessary in high risk patients. .A Batt M; Declemy S; Persch M; Hassen-Khodja R; Daune B; Avril G; Gagliardi JM; Le Bas P. .I 275319 .U 91009451 .S J Cardiovasc Surg (Torino) 9101; 31(4):453-6 .M Aged; Anastomosis, Surgical/*AE; Aneurysm/*ET/SU; Blood Vessel Prosthesis/AE; Female; Femoral Artery/PA/*SU; Human; Male; Middle Age; Prosthesis Failure; Reoperation; Sutures. .T Femoral noninfected anastomotic aneurysms. A report of 56 cases. .P JOURNAL ARTICLE. .W Fifty-six femoral non infected anastomotic false aneurysms (FAAs) were observed in 49 patients admitted to the Institute of Vascular Surgery, University of Milan, from 1975 to 1988; in 6 patients they were bilateral. These aneurysms developed after primary revascularization procedures at a mean interval of 66 months (range 12 to 156 months); one recurred after reparative surgery. Forty-four FAAs (78.6%) were asymptomatic, whereas 3 (5.3%) were complicated by acute expansion and 9 (16.1%) by thrombosis. Host vessel degeneration was the cause of aneurysm formation in most cases. A history of hypertension was present in 30% of the patients. All anastomotic aneurysms were operated upon except for one small aneurysm that was asymptomatic. In 5 patients aneurysm resection was carried out on both sides. The surgical technique was endoaneurysmectomy in all the cases with insertion of an interposition graft in 48 cases, a fabric patch in 2 cases and prosthesis re-anastomosis in 5 cases. One case of peripheral embolization occurring in the early postoperative period was successfully treated and there was no operative mortality. In our opinion elective repair of these aneurysms should be recommended whenever possible because of their propensity to develop serious complications and the operative morbidity is low. .A Agrifoglio G; Costantini A; Lorenzi G; Agus GB; Castelli PM; Zaretti D. .I 275320 .U 91009452 .S J Cardiovasc Surg (Torino) 9101; 31(4):457-61 .M Amputation; Aneurysm/ET/SU; Arteriovenous Fistula/ET/SU; Human; Popliteal Artery/*IN; Triage; Vascular Surgery/*MT. .T The management of aneurysms and arterio-venous fistulae of the popliteal artery arising from war trauma. Emphasis on sigmoid operative approach. .P JOURNAL ARTICLE. .W Between 1986-1988, 600 vascular cases arising from the Iran-Iraq conflict were dealt with within an 18 month period and 60 cases of popliteal artery and/or venous disruption were encountered presenting at variable times after injury. A policy of management between the forward and base hospital surgical teams was introduced, observing the following broad categorizations: (a) assessment/referral, (b) assessment/fasciotomy/referral, (c) immediate operation/referral for further operation/review/management. Two types of incision were used to enter the popliteal fossa: (a) a medial incision and (b) a sigmoid posterior incision (which we now favor). The results of this strategy of management and operative technique (when compared with our previous experience within the same time frame) suggested an improved outcome. Fifty-four out of 60 cases had a satisfactory operative result with below-knee amputation being required in only four cases and higher amputations in two others. No operative or postoperative deaths occurred. The implementation of this "vetting policy" at the front line appeared to reduce the number of amputations and assisted the clarification of management criteria in assessing limb viability at the forward hospital when a large number of casualties were being received. Operative access using the sigmoid posterior incision was not associated with any complications, offered better exposure than the medial incision and was technically easier for the surgeon to perform. .A Hamza N; Marath A; Al-Fakhry MR. .I 275321 .U 91009453 .S J Cardiovasc Surg (Torino) 9101; 31(4):462-8 .M Adult; Aged; Aged, 80 and over; Amputation; Blood Vessel Prosthesis/*; Female; Femoral Artery/*SU; Graft Occlusion, Vascular/TH; Human; Intermittent Claudication/*SU; Male; Middle Age; Polyethylene Terephthalate; Polytetrafluoroethylene; Popliteal Artery/*SU; Postoperative Complications/MO; Prosthesis Failure; Reoperation; Retrospective Studies; Survival Rate; Thigh. .T Prosthetic above-knee femoropopliteal bypass for intermittent claudication. .P JOURNAL ARTICLE. .W There is no consensus about the most appropriate management of the patient with intermittent claudication due to a superficial femoral artery occlusion. To evaluate the natural history of prosthetic above-knee femoropopliteal (AKFP) bypass, 200 operations for intermittent claudication were reviewed. One hundred AKFP bypasses were done with PTFE and 100 with dacron. In the 30 day postoperative period, four PTFE and three dacron grafts occluded without consequence and only one patient died. Analysis of results by the life-table method demonstrated statistically similar primary graft patency rates at five years (PTFE 65% SE +/- 6.5, dacron 57% +/- 6.2) and ten years (PTFE 31% +/- 18/9, dacron 32% +/- 13.2) (p greater than 0.10). Redo procedures (e.g., thrombectomy, angioplasty) were necessary on 21 grafts (12 PTFE, 9 dacron) and "secondary" patency rates at five years were 76% PTFE and 62% dacron; no grafts which required a redo procedure were patent at ten year follow-up. Major amputations during ten year follow-up were necessary in 16 (8%) patients; all amputations were in diabetic patients. Survival rates were 79% at five and 42% at ten years. An anticipated, the leading cause of death was cardiac related (25 patients); 28 (14%) patients underwent aortocoronary bypass during follow-up. A prosthetic AKFP bypass graft is a safe and durable operation which provides relief from the symptoms of intermittent claudication while allowing for the preservation of the saphenous vein for use later in the coronary or infrapopliteal circulations, should the need arise. These results indicate that the risk of amputation after AKFP is no greater than the natural history of untreated claudication; however, AKFP offers a significant improvement in life-style. .A Rosenthal D; Evans RD; McKinsey J; Seagraves MA; Lamis PA; Clark MD; Daniel WW. .I 275322 .U 91009454 .S J Cardiovasc Surg (Torino) 9101; 31(4):469-73 .M Antibiotics/TU; Blood Vessel Prosthesis/*AE; Cystoscopy/*AE; Female; Human; Male; Microbial Sensitivity Tests; Middle Age; Prospective Studies; Septicemia/DT/*ET/MI; Support, Non-U.S. Gov't. .T Selection of antibiotic coverage in vascular patients undergoing cystoscopy. .P JOURNAL ARTICLE. .W Bacteremic seeding of prosthetic vascular grafts represents a cause for graft infection; transurethral procedures account for one source of bacteremia. Therefore, a prospective study of 200 patients undergoing cystoscopy was conducted to identify the incidence of bacteruria and factors associated with it, organisms involved and their antibiotic sensitivities. Positive cultures were found in 21%. The incidence was 64% in in-patients and 8% in out-patients. Positive cultures were found in 12% of patients who received antibiotics and 29% who did not. Four percent showed signs of bacteremia. The cultures identified both Gram positive and negative organisms; multiple organisms grew in 22%. Gram negative organisms were more common in in-patients. Candida grew in 8%. The Gram positive organisms were sensitive to ampicillin (92%), sulfatrimethoprim (75%) and cefazolin (60%); Gram negative to aminoglycosides (100%) and cefazolin (92%). In view of the unpredictable and multiple organisms, it is recommended that pre-cystoscopy cultures be performed and specific antibiotic coverage be based on the sensitivities. .A Wooster DL; Krajden S. .I 275323 .U 91009455 .S J Cardiovasc Surg (Torino) 9101; 31(4):474-8 .M Aneurysm, Dissecting/DI; Aorta, Thoracic; Aortic Aneurysm/DI; Case Report; Diagnosis, Differential; Female; Hemorrhage/DI/*ET/SU; Human; Middle Age; Neurofibroma/*CO/PA; Spinal Neoplasms/*CO/PA; Thoracic Vertebrae/*. .T Unusual haemostasis for an unusual tumour. Catastrophic bleeding from a tactile neurofibroma affecting the thoracic vertebrae. Case report. .P JOURNAL ARTICLE. .W The symptomatology of a typical acute descending thoracic aorta dissection was imitated by profuse haemorrhage caused by a benign tumour composed almost exclusively of Wagner-Meissner like tactile corpuscles and fatty tissue. The tumour caused extensive destruction of the bodies of the fifth and sixth thoracic vertebrae at the level of the vertebro-costal articulation. Emergency cross clamping of the descending aorta and haemostasis of the bleeding from osteal defects by tamponade with bone polymethyl methacrylate appeared the only way to control the life threatening haemorrhage. It seems that an intrathoracic tactile neurofibroma with a similar case history has not been reported till now. .A Vincent JG; Naudin ten Cate L; Kaan GL; van Horn JR; Pruszczynski M. .I 275324 .U 91009456 .S J Cardiovasc Surg (Torino) 9101; 31(4):479-81 .M Aged; Aged, 80 and over; Aorta, Abdominal/*; Aortic Rupture/CO/*RA; Arteriovenous Fistula/ET/*RA; Case Report; Diagnostic Errors; Human; Male; Renal Veins/*; Tomography, X-Ray Computed/*. .T Spontaneous rupture of an aortic aneurysm into the left renal vein. A diagnostic challenge. .P JOURNAL ARTICLE. .W Rupture of an aortic aneurysm into a renal vein presents a rare and difficult diagnostic problem. Often, therapy is delayed because the patient is thought to have a urologic problem. In this instance, CT scan provided useful clues leading to the diagnosis of this entity, and its rapid treatment. To our knowledge, this is the first CT scan done in a patient with aorto-renal vein fistula. .A Katz SG; Kohl RD. .I 275325 .U 91009457 .S J Cardiovasc Surg (Torino) 9101; 31(4):482-5 .M Adolescence; Case Report; Embolism/*ET; Femoral Artery; Heart Injuries/*CO; Human; Male; Wounds, Gunshot/*CO. .T Plastic bullet arterial embolization following gunshot injury to the heart. Case report and review of the literature. .P JOURNAL ARTICLE; REVIEW; REVIEW OF REPORTED CASES. .W A plastic bullet penetrating the heart through the right ventricle embolized to the right profunda. Suture of the heart and extraction of the bullet resulted in uneventful recovery. The literature revealed 21 instances of embolization following proven heart penetration, in two cases through the right ventricle. .A Walden R; Lynn M; Golan M; Garniek A. .I 275326 .U 91009458 .S J Cardiovasc Surg (Torino) 9101; 31(4):486-91 .M Adolescence; Adult; Age Factors; Female; Heart Failure, Congestive/SU; Heart Transplantation/MO/*PH; Heart, Artificial/*/SN; Human; Male; Middle Age; Postoperative Complications/MO/PC; Survival Rate; Thromboembolism/PC. .T Mechanical circulatory support as a bridge to transplantation: current status of total artificial heart in 1989 and determinants of survival. .P JOURNAL ARTICLE. .W Since April 1986, 40 total artificial hearts (TAH) were implanted as a bridge to transplantation in our institution. In an attempt to identify factors affecting survival of TAH recipients we reviewed our experience over 1000 days of mechanical support. There was no postoperative bleeding requiring surgery nor were there any clinical episodes of thromboembolic complications. Over a total functioning period greater than 3 years there were no mechanical failures in the driving system but one artificial ventricle had to be replaced because of mechanical dysfunction. Infections and multiple organ failure were the primary causes of morbidity and mortality during mechanical support. When the patients who underwent staged transplantation (no. 17) were compared with those who died during mechanical support (no. 23) there were no differences in TAH driving mode or hemodynamic variables between the groups. Although preoperative pulmonary, hepatic and renal functions were found to be similar between the groups, there were significant differences in the early evolution (3 days) of hepatic and renal functions following TAH implant (p less than 0.01). Urinary output was found to be the earliest variable discriminating recovery and survival (p less than 0.01). Finally, univariate analysis indicated age (less than 40 vs greater than 40 years) and modality of cardiac decompensation (acute vs chronic) as the most important factors affecting survival after TAH implantation. Since young patients (less than 40 years of age) with acute decompensation were successfully transplanted in 82% of cases while 100% of older patients with chronic decompensation died before or after transplantation, TAH should be advised in young patients with acute or chronic heart failure and in selected older candidates with recent, acute cardiac failure. .A Muneretto C; Rabago G Jr; Pavie A; Leger P; Gandjbakhch I; Sasako Y; Tedy G; Bors V; Desruennes M; Szefner J; et al. .I 275327 .U 91009459 .S J Cardiovasc Surg (Torino) 9101; 31(4):492-7 .M Aged; Angina Pectoris/EP/SU; Coronary Artery Bypass/*AE/MO; Coronary Disease/EP/*SU; Emergencies; Female; Human; Incidence; Male; Middle Age; Reoperation/AE/MO; Risk Factors. .T Clinical outcome of emergency repeat coronary artery bypass surgery. .P JOURNAL ARTICLE. .W To determine the clinical outcome of patients requiring emergency repeat coronary artery bypass graft (CABG) procedures, we reviewed 23 such procedures performed for ongoing myocardial ischemia refractory to medical management. The operative mortality was 17%. On follow-up, an average of 24.9 months after emergency reoperation, 14 of the 19 survivors (74%) had recurrent angina. As compared to a randomly selected group of 25 patients who underwent elective repeat CABG procedures during the same time period, the incidence of late cardiac events was significantly higher (79% in the emergency group, 30% in the elective surgery group) and fewer patients had received internal mammary artery (IMA) grafts (9% vs 52%). Emergency repeat CABG operations have considerable operative mortality and poor postoperative functional results with the majority of survivors developing recurrent ischemic syndromes within a short period of time. .A Lemmer JH Jr; Ferguson DW; Rakel BA; Rossi NP. .I 275328 .U 91009460 .S J Cardiovasc Surg (Torino) 9101; 31(4):498-504 .M Age Factors; Child; Child, Preschool; Female; Heart Septal Defects/*SU; Human; Infant; Male; Mitral Valve/*AB/PP/SU; Mitral Valve Insufficiency/ET; Pulmonary Circulation; Tricuspid Valve/*AB/PA/SU; Vascular Resistance. .T Primary repair for complete atrioventricular canal: recommendation for early primary repair. .P JOURNAL ARTICLE. .W Forty patients with complete atrioventricular canal (CAVC) underwent primary repair at Fukuoka Children's Hospital in Fukuoka, Japan, between August 1, 1981 and July 31, 1989. The age at repair ranged from 2 months to 6 years (mean 19 months); weight ranged from 2.3 to 22 kg. The surgical mortality was 2.5%. Justification for early primary repair was examined. Eleven patients underwent repair before 6 months of age (Group 1), 12 patients, between 7 and 11 months of age (Group 2), and 17 patients, after 12 months of age (Group 3). Degenerative changes in the atrioventricular valve increased significantly as age at repair increased (p less than 0.05 Group 1 versus Group 3). The incidence of residual mitral regurgitation tended to increase in the order of Group 1, 2 and 3, though the degree ranged from trivial to mild. Study of the left atrium/aorta ratio by echocardiography revealed that stable values of around 1.1 in Groups 1 and 2 and around 1.3 in Group 3 continued during the follow-up period of 3 years. Assessment of the diameter of the repaired mitral valve in the mean interval of 26 months in groups 1 and 2 revealed normal growth of the mitral valve annulus. The angle between the repaired mitral valve and ventricular septum, which can be affected by the growth of the ventricular septum, converged to normal range in the mean interval of 26 months. Postoperative pulmonary vascular resistance in Groups 2 and 3 was higher at 4.4 +/- 2.3 and 6.3 +/- 2.2, respectively, than in Group 1 at 3.3 +/- 2.2 (p less than 0.01 versus Group 3).(ABSTRACT TRUNCATED AT 250 WORDS) .A Yasui H; Nakamura Y; Kado H; Yonenaga K; Shiokawa Y; Fusazaki N; Sunagawa H; Tokunaga K. .I 275329 .U 91009461 .S J Cardiovasc Surg (Torino) 9101; 31(4):505-8 .M Adult; Aortic Valve/*SU; Enzymes/BL; Extracorporeal Circulation/*AE; Female; Heart Enlargement/*CO; Heart Valve Diseases/SU; Heart Valve Prosthesis; Human; Intraoperative Period; Male; Middle Age; Myocardial Reperfusion Injury/BL/*ET; Myoglobin/BL; Postoperative Period; Regression Analysis. .T Perioperative myocardial injury in patients undergoing aortic valve replacement. .P JOURNAL ARTICLE. .W In cases of myocardial hypertrophy myocardial protection may be insufficient. In order to determine the factors responsible for myocardial injury we assessed myocardial injury in 54 patients undergoing isolated aortic valve replacement. In all cases hypothermic cardioplegic arrest was induced. At 13 different times we measured the serum level of creatine-kinase (CK), myocardial bound creatine-kinase (CKmb), lactic dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (alpha-HBDH), glutamic oxaloacetic transferase (GOT) and myoglobin. The mean duration of ischemia was 52.6 +/- 16.2 minutes and the mean time of extracorporeal circulation was 85.85 +/- 20.25 minutes. By performance of a multiple regression analysis a significant correlation between ischemia and LDH and alpha-HBDH was found; CK, GOT, LDH and alpha-HBDH correlated with duration of extracorporeal circulation. In none of the patients was a low cardiac output syndrome observed. From our results we conclude that in our study myocardial protection was sufficient and therefore the detrimental effects of extracorporeal circulation were the determining factors of enzyme release. .A Goerlach G; Temme H; Golf S; Dapper F; Scheld HH; Hehrlein FW. .I 275330 .U 91009462 .S J Cardiovasc Surg (Torino) 9101; 31(4):509-11 .M Adult; Carbon; Evaluation Studies; Female; Follow-Up Studies; Heart Valve Prosthesis/*/AE/MO; Hemodynamics; Human; Male; Middle Age; Mitral Valve; Polyethylene Terephthalate. .T Clinical and functional evaluation of the Carbomedics Prosthetic Heart Valve in the mitral position. Preliminary results. .P JOURNAL ARTICLE. .W The Carbomedics Prosthetic Heart Valve is a new bileaflet pyrolite carbon prosthesis. This paper reports the preliminary results in 40 patients who underwent mitral valve replacement (MVR) using the Carbomedics Valve in 1988. The operative mortality rate was 5% and the early results have been encouraging, with no valve related complications observed in the first post-operative year. .A Subotic S; Petrovic P; Boskovic D; Obrenovic B; Sindjelic R; Lovric Z; Djukic P; Vranes M; Curcic S; Matic A. .I 275331 .U 91009463 .S J Cardiovasc Surg (Torino) 9101; 31(4):512-7 .M Adolescence; Adult; Aged; Female; Follow-Up Studies; Human; Intraoperative Period/MO; Male; Methods; Middle Age; Postoperative Complications/*MO; Reoperation; Risk Factors; Survival Rate; Tricuspid Valve Insufficiency/*SU. .T The De Vega tricuspid annuloplasty. Perioperative mortality and long term follow-up. .P JOURNAL ARTICLE. .W One hundred and fifty-three patients undergoing De Vega tricuspid annuloplasty, with or without other associated cardiac procedures between January, 1979, and June, 1987, were evaluated. There were 136 hospital survivors. The follow-up was 98.1% complete for a mean of 3.7 years/patient. Operative mortality was 11.1%; preoperative NYHA class and length of CPB were significant risk factors of perioperative mortality. The actuarial survival of operative survivors at 9 years was 73.5 +/- 11.8%. There were 7 late cardiac deaths among a total of 12 late deaths. Eleven patients required reoperation (2.1 +/- 0.6% patient-year). In seven patients it was necessary for recurrence of tricuspid regurgitation; six of these had also a mitral prosthesis malfunction or a periprosthetic leak. Residual tricuspid regurgitation was judged as mild, moderate or severe in 29.9%, 11.9% and 4.3% of the patients respectively. De Vega tricuspid annuloplasty is the method of choice for mild and moderate tricuspid insufficiency; in selected cases, with a more severe degree of regurgitation, better results could be achieved with a different surgical approach. .A De Paulis R; Bobbio M; Ottino G; Donegani E; Di Rosa E; Casabona R; Girotto M; Morea M. .I 275332 .U 91009464 .S J Cardiovasc Surg (Torino) 9101; 31(4):518-24 .M Adolescence; Adult; Aged; Echinococcosis/*RA; Female; Heart Diseases/*RA; Human; Male; Prospective Studies; Tomography, X-Ray Computed/*. .T Cardiac echinococcosis: the diagnostic value of computed tomography scanning. .P JOURNAL ARTICLE. .W The diagnosis of cardiac hydatid disease is a difficult one. Conventional and specific cardiac investigations are not pathognomonic of this disease. In this report, the diagnostic value of computed tomography (CT) scanning was prospectively investigated in seven patients. In five patients, the diagnosis was confirmed surgically. The CT-information obtained correlated accurately to the operative findings. In all the patients, CT-densities of the lesions were measured and were found to coincide with values of mean CT-densities of hydatid cysts elsewhere in the body. The capability of measuring tissue densities is unique to CT-scanning and have been emphasized in this report. .A Samarrai AA; Hussain WM; al-Shaarbaf HH; Ismail MA. .I 275333 .U 91009465 .S J Cardiovasc Surg (Torino) 9101; 31(4):525-30 .M Adolescence; Adult; Aged; Female; Heart Injuries/*DI/ET/MO; Human; Male; Middle Age; Pericardium/*IN; Rupture; Thoracotomy; Wounds, Nonpenetrating/*CO/MO. .T Blunt traumatic pericardial rupture. A ten-year experience 1979 to 1989. .P JOURNAL ARTICLE. .W Blunt traumatic pericardial rupture is rarely diagnosed preoperatively and is associated with high mortality. During a ten-year period from 1979 to 1989 over 20,000 patients were admitted to a major trauma center and 22 were found to have blunt traumatic pericardial rupture. Sixteen of the 22 (72.7%) were injured in vehicle accidents, 3 (13.6%) in motorcycle crashes, and 2 (9.1%) in falls; 1 (4.5%) was crushed. Eighteen (81.8%) were diagnosed intraoperatively during resuscitation or surgery for associated injuries, and four (18.1%) were diagnosed preoperatively with pericardial window. Eighteen were males and four were females. The median age was 40.14 years (range, 17 to 68). The tears were found at the following sites: left pleuropericardial (14/22 [64%]), diaphragmatic (4/22 [18%]), right pleuropericardial (2/22 [9%]), and superior mediastinal (2/22 [9%]). Associated cardiac injuries were found in only 5 of the 22 (22.7%); all of those patients died. The overall mortality rate was 63.6% (14/22). A high index of suspicion should alert the trauma surgeon to make the diagnosis intraoperatively during emergency surgical resuscitation in the hemodynamically unstable patient and by pericardial window in the stable patient. .A Fulda G; Rodriguez A; Turney SZ; Cowley RA. .I 275334 .U 91009466 .S J Cardiovasc Surg (Torino) 9101; 31(4):531-2 .M Acyclovir/TU; Aged; Cardiopulmonary Bypass/*AE; Case Report; Female; Herpes Zoster/DT/*ET; Human; Skin Diseases/ET. .T Disseminated cutaneous herpes zoster following cardiac surgery. .P JOURNAL ARTICLE. .W Our case report describes disseminated cutaneous Herpes Zoster in the early post-operative period following cardiac surgery with cardiopulmonary bypass. This has not been reported previously in the absence of immunosuppressive therapy. Despite associated neurologic and respiratory impairment, our patient was treated successfully with intravenous Acyclovir and subsequently discharged. .A Dirbas FM; Swain JA. .I 275335 .U 91009467 .S J Cardiovasc Surg (Torino) 9101; 31(4):533-5 .M Aged; Case Report; Coronary Vessels/*IN; Human; Male; Myocardial Infarction/ET; Sutures/*; Tricuspid Valve/*SU. .T Right coronary artery injury during tricuspid valve annuloplasty. .P JOURNAL ARTICLE. .W An unusual complication after tricuspid valve annuloplasty is described where a ring suture ligated right coronary artery and precipitated myocardial infarct and patient death. The need for caution to prevent this complication with such surgery is emphasized. .A Rubens FD; Bedard P; Walley VM. .I 275336 .U 91009468 .S J Cardiovasc Surg (Torino) 9101; 31(4):536-40 .M Case Report; Child; Child, Preschool; Echocardiography; Electrocardiography; Female; Fibroma/*DI/SU; Heart Neoplasms/*DI/SU; Human; Male. .T Left ventricular fibroma: echocardiographic diagnosis and successful surgical excision in three cases. .P JOURNAL ARTICLE. .W The management of three patients with left ventricular fibromas is outlined. All were asymptomatic children. Routine chest radiography suggested cardiac masses. M-mode and two-dimensional echocardiography were valuable adjuncts to conventional angiography in assessing these children. Electrocardiographic changes, present in all cases, were shown to regress postoperatively. We stress the importance of these noninvasive aids in the initial investigation and outline our operative methods of reconstruction. .A Brown IW; McGoldrick JP; Robles A; Curella GW; Gula G; Ross DN. .I 275337 .U 91009469 .S J Cardiovasc Surg (Torino) 9101; 31(4):541-4 .M Amyloidosis/*PA; Bioprosthesis; Blood Vessel Prosthesis; Case Report; Coronary Artery Bypass; Coronary Vessels/PA; Human; Male; Middle Age; Saphenous Vein/*PA. .T Amyloidosis in saphenous vein aortocoronary bypass grafts. .P JOURNAL ARTICLE. .W A patient in whom idiopathic amyloidosis of aortocoronary saphenous vein grafts was found at autopsy two years after myocardial revascularization due to coronary atherosclerosis is reported. Idiopathic generalized immunocyte derived amyloidosis extensively studied at autopsy was obviously present at the time of surgery although it remained unnoticed macroscopically in the inserted graft. It appears that simultaneously with arterialization further deposition and also significant redistribution of amyloid within the walls of the vein grafts additionally took place after their insertion. It seems interesting that in spite of the amyloidosis the grafts functioned well and were found patent two years after surgery. .A Zemva A; Ferluga D; Zorc M; Popovic M; Porenta OV; Radovanovic N. .I 275338 .U 91009803 .S J Clin Invest 9101; 86(4):1015-22 .M Human; Receptors, Antigen, T-Cell/AN/GE/*PH; Signal Transduction; Support, U.S. Gov't, P.H.S.. .T Structure and function of the T cell antigen receptor. .P JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC. .A Weiss A. .I 275339 .U 91009804 .S J Clin Invest 9101; 86(4):1023-9 .M Animal; Desmopressin/PD; Down-Regulation (Physiology); Hyponatremia/*ME; Male; Neurophysins/BI/GE; Osmolar Concentration; Oxytocin/BI/GE; Pressoreceptors/PH; Rats; Rats, Inbred Strains; RNA, Messenger/AN; Support, U.S. Gov't, P.H.S.; Vasopressins/*BI/GE. .T Hyponatremia in rats induces downregulation of vasopressin synthesis. .P JOURNAL ARTICLE. .W Hyponatremia due to inappropriate secretion of vasopressin is a common disorder in human pathophysiology, but vasopressin synthesis during hypoosmolality has not been investigated. We used a new method to quantitate synthesis of vasopressin in rats after 3, 7, and 14 d of hyponatremia induced by administering dDAVP (a vasopressin agonist) and a liquid diet. Vasopressin synthesis was completely turned off by 7 d. Vasopressin mRNA levels in the hypothalamus paralleled the reduction in synthesis and were reduced to levels of only 10-15% of the content in control rats. When hyponatremia was corrected by withdrawal of dDAVP, vasopressin mRNA slowly returned to normal over 7 d. The observation that vasopressin synthesis can be so completely turned off leads to several conclusions: under normal physiological conditions the neurohypophysis is chronically upregulated; there must be an osmotic threshold for initiation of vasopressin synthesis (and release); the large store of hormone in the posterior pituitary is essential for vasopressin to be available during times of decreased synthesis; and, finally, some nonosmolar stimulus for synthesis must be present during clinical disorders when vasopressin is secreted (and synthesized) despite hypoosmolality. .A Robinson AG; Roberts MM; Evron WA; Verbalis JG; Sherman TG. .I 275340 .U 91009805 .S J Clin Invest 9101; 86(4):1030-7 .M Electron Spin Resonance; Human; Hydroxides/*; Iron/*PD; Iron Chelates/*PD; Neutrophils/PH; Phenols/*PD; Pseudomonas Infections/*ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Possible role of bacterial siderophores in inflammation. Iron bound to the Pseudomonas siderophore pyochelin can function as a hydroxyl radical catalyst. .P JOURNAL ARTICLE. .W Tissue injury has been linked to neutrophil associated hydroxyl radical (.OH) generation, a process that requires an exogenous transition metal catalyst such as iron. In vivo most iron is bound in a noncatalytic form. To obtain iron required for growth, many bacteria secrete iron chelators (siderophores). Since Pseudomonas aeruginosa infections are associated with considerable tissue destruction, we examined whether iron bound to the Pseudomonas siderophores pyochelin (PCH) and pyoverdin (PVD) could act as .OH catalysts. Purified PCH and PVD were iron loaded (Fe-PCH, Fe-PVD) and added to a hypoxanthine/xanthine oxidase superoxide- (.O2-) and hydrogen peroxide (H2O2)-generating system. Evidence for .OH generation was then sought using two different spin-trapping agents (5.5 dimethyl-pyrroline-1-oxide or N-t-butyl-alpha-phenylnitrone), as well as the deoxyribose oxidation assay. Regardless of methodology, .OH generation was detected in the presence of Fe-PCH but not Fe-PVD. Inhibition of the process by catalase and/or SOD suggested .OH formation with Fe-PCH occurred via the Haber-Weiss reaction. Similar results were obtained when stimulated neutrophils were used as the source of .O2- and H2O2. Addition of Fe-PCH but not Fe-PVD to stimulated neutrophils yielded .OH as detected by the above assay systems. Since PCH and PVD bind ferric (Fe3+) but not ferrous (Fe2+) iron, .OH catalysis with Fe-PCH would likely involve .O2(-)-mediated reduction of Fe3+ to Fe2+ with subsequent release of "free" Fe2+. This was confirmed by measuring formation of the Fe2(+)-ferrozine complex after exposure of Fe-PCH, but not Fe-PVD, to enzymatically generated .O2-. These data show that Fe-PCH, but not Fe-PVD, is capable of catalyzing generation of .OH. Such a process could represent as yet another mechanism of tissue injury at sites of infection with P. aeruginosa. .A Coffman TJ; Cox CD; Edeker BL; Britigan BE. .I 275341 .U 91009806 .S J Clin Invest 9101; 86(4):1038-45 .M Animal; Antigens, Viral/AN; Carbon Tetrachloride/*TO; Female; Hepatitis, Viral, Animal/*ET/MO; Liver/DE/*MI; Mice; Microscopy, Electron; Reoviridae/IM/IP/*PY; Reovirus Infections/CO; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Synergism between hepatic injuries and a nonhepatotropic reovirus in mice. Enhanced hepatic infection and death. .P JOURNAL ARTICLE. .W Reovirus type 1, after intravenous inoculation in the adult mouse, is secreted via bile into the intestine in an infectious form. Although reovirus type 1 is rapidly removed from systemic circulation by the liver and the lung, very few hepatocytes express reovirus antigen during infection. In intestinal cells, reovirus replicates selectively in the crypts. This site preference may be due to active cell proliferation in the crypts. We hypothesized that the state of the cell may affect virus replication and tested this hypothesis by using chemical and surgical means to increase hepatic mitotic activity. Adult mice were treated with carbon tetrachloride or surgical trauma, inoculated with reovirus type 1 intravenously, and subsequently killed. Virus antigen was identified using a highly specific immunohistochemical technique. Liver sections were stained using immunoperoxidase with specific rabbit antireovirus antibody. Hepatotoxin and surgical trauma increase reovirus antigen detection in both Kupffer cells and hepatocytes. Only the sequential administration of CCl4 and virus caused mortality at doses sublethal for each alone. These data demonstrate a synergism between hepatic injury and reovirus which results in a significant increase in the magnitude of viral infection and contributes to mortality. Such synergism may be important in idiopathic liver disease. .A Piccoli DA; Witzleben CL; Guico CJ; Morrison A; Rubin DH. .I 275342 .U 91009807 .S J Clin Invest 9101; 86(4):1046-54 .M Adolescence; Adult; Child; Collagen/*AN/ME; Diabetes Mellitus, Insulin-Dependent/CO/*ME; Dipeptides/AN; Female; Glycosylation; Human; Lysyl Oxidase/*PH; Male; Pyridines/AN; Skin/*CH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Relationship between the content of lysyl oxidase-dependent cross-links in skin collagen, nonenzymatic glycosylation, and long-term complications in type I diabetes mellitus. .P JOURNAL ARTICLE. .W Many abnormalities in collagen have been reported in insulin-dependent diabetes mellitus, some or all of which have been attributed to increased cross-linking. Although recent work has focused on the role of glucose-derived collagen cross-links in the pathogenesis of diabetic complications, relatively few studies have investigated the role of lysyl oxidase-dependent (LOX) cross-links. In the present study, LOX cross-links and nonenzymatic glycosylation were quantified in skin collagen from diabetic subjects. There was an increase in the difunctional cross-link dihydroxylysinonorleucine (DHLNL) as well as in one of its trifunctional maturation products, hydroxypyridinium. All other LOX crosslinks were normal. Nonenzymatic glycosylation was increased in diabetic skin collagen, and this increase was correlated with increases in DHLNL (P less than 0.001). The biochemical results were examined for correlations with clinical data from the same subjects. Increases in DHLNL content were associated with duration of diabetes (P less than 0.003), glycohemoglobin levels (P less than 0.001), hand contractures (P less than 0.05), skin changes (P less than 0.005), and microalbuminuria (P less than 0.01). In nondiabetic subjects age was not correlated with collagen cross-link content with the exception that his-HLNL increased with age (r = 0.79, P less than 0.02). In diabetic subjects, PA levels decreased with age (r = 0.51, P less than 0.02). With increased duration of diabetes, DHLNL content was increased (r = 0.55, P less than 0.003) and OHP was increased (r = 0.59, P less than 0.01), whereas PA levels were decreased (r = -0.48, P less than 0.04). Nonenzymatic glycosylation of collagen was also increased with increased duration of diabetes (hex-lys, r = 0.47, P less than 0.02; hex-hyl, r = 0.39, P less than 0.05). We conclude that: (a) lysyl oxidase-dependent cross-linking is increased in skin collagen in diabetes and (b) that these changes in skin collagen are correlated with duration of diabetes, glycemic control, and long-term complications. .A Buckingham B; Reiser KM. .I 275343 .U 91009808 .S J Clin Invest 9101; 86(4):1055-64 .M Collagen/ME; Epithelium/ME; Human; Lung/ME; Macrophages/ME; Platelet-Derived Growth Factor/AN/*GE; Proto-Oncogene Proteins/AN/*GE; Proto-Oncogenes/*; Pulmonary Fibrosis/*ME; Receptors, Endogenous Substances/GE; RNA, Messenger/AN; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Platelet-derived growth factor in idiopathic pulmonary fibrosis. .P JOURNAL ARTICLE. .W Fibrosis is a complex process involving an inflammatory reaction, fibroblast proliferation, and abnormal accumulation of interstitial collagens. Mononuclear cells are usually present in lung fibrosis. Activated monocytes and macrophages in culture have been shown to produce several growth factors including platelet-derived growth factor (PDGF). PDGF is a potent mitogen and chemoattractant for fibroblasts and smooth muscle cells and a stimulator of collagen synthesis. We have studied the expression of c-sis/PDGF-2 mRNA in lung tissues derived from five patients with idiopathic pulmonary fibrosis (IPF) and from four control individuals without IPF. Northern blot analysis of specimens obtained from four patients with IPF revealed the expression of the c-sis/PDGF-2 protooncogene. A control lung tissue without IPF did not express the c-sis protooncogene. In situ hybridization extended these studies demonstrating the expression of the c-sis mRNA in the five specimens with IPF but not in the four control specimens without IPF. The expression of c-sis mRNA was localized primarily in the epithelial cells. Invading alveolar macrophages also expressed c-sis mRNA. The expression of c-sis mRNA was accompanied by the expression of PDGF-like proteins in lung specimens with IPF but not in control lung specimens. These findings demonstrate the in vivo expression of the c-sis/PDGF-2 protooncogene and the production of PDGF-like proteins in the epithelial cells and macrophages of the fibrotic tissue. This localized and sustained production of PDGF-like mitogen may constitute an important contributing factor in the abnormal fibroblast proliferation and collagen production, events associated with pulmonary fibrosis. .A Antoniades HN; Bravo MA; Avila RE; Galanopoulos T; Neville-Golden J; Maxwell M; Selman M. .I 275344 .U 91009809 .S J Clin Invest 9101; 86(4):1065-75 .M Animal; Bronchoalveolar Lavage Fluid/CH/CY; Chemotaxis/*; Complement 5/*PH; Female; Fibronectins/AN/IM/*PH; Lung/CY; Male; Monocytes/*PH; Neutrophils/PH; Peptide Fragments/*PH; Peptide Peptidohydrolases/PH; Rabbits; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Fibronectin fragments containing the RGDS cell-binding domain mediate monocyte migration into the rabbit lung. A potential mechanism for C5 fragment-induced monocyte lung accumulation. .P JOURNAL ARTICLE. .W Many inflammatory processes are characterized by an early phase of neutrophil migration and a later phase of monocyte migration into the inflammatory site. Mechanisms that govern the transition between phases are the subject of these investigations. Acute lung inflammation induced by C5 fragments in the rabbit leads to an initial neutrophil influx and plasma leakage into the alveolar space, followed by monocyte influx that we have previously shown to be dependent on prior emigration of neutrophils. Neutrophil enzymes are known to cleave intact fibronectin into fragments that are monocyte chemotaxins in vitro. Accordingly, generation of appropriate fibronectin fragments in situ by proteolytic enzymes from infiltrating neutrophils might represent a potential mechanism for attraction of monocytes into the lung. The studies reported herein demonstrate that a 120-kD fragment of fibronectin containing the RGDS fibroblast cell-binding domain induced monocyte migration into the rabbit lung in vivo. Intact fibronectin was inactive. A significant proportion of the monocyte migration was neutrophil independent. Intact fibronectin was present in bronchoalveolar lavage fluid from C5 fragment-treated animals rendered neutropenic, but absent in lavage from normal C5 fragment-treated animals. Fibronectin fragments were present in bronchoalveolar lavage fluid from both C5 fragment-treated and control rabbits. In addition, the amount of fibronectin was significantly increased in lavage of C5 fragment-treated normal but not neutropenic animals. Monoclonal antibodies directed against an epitope of fibronectin containing the RGDS cell-binding domain significantly inhibited the C5 fragment-induced monocyte migration, but not neutrophil migration. These studies suggest that chemotactic fibronectin fragments may in part be responsible for the recruitment of monocytes into areas of acute lung inflammation. .A Doherty DE; Henson PM; Clark RA. .I 275345 .U 91009810 .S J Clin Invest 9101; 86(4):1076-83 .M Animal; Bicarbonates/*ME; Biological Transport; Carbonates/ME; Hydrogen-Ion Concentration; Kidney Cortex/*ME; Male; Potassium/*PH; Protons; Rats; Rats, Inbred Strains; Sodium/*ME; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Potassium depletion increases luminal Na+/H+ exchange and basolateral Na+:CO3=:HCO3- cotransport in rat renal cortex. .P JOURNAL ARTICLE. .W Most HCO3- reabsorption in proximal tubules occurs via electroneutral Na+/H+ exchange in brush border membranes (BBMS) and electrogenic Na+:CO3=:HCO3- cotransport in basolateral membranes (BLMS). Since potassium depletion (KD) increases HCO3- reabsorption in proximal tubules, we evaluated these transport systems using BBM and BLM vesicles, respectively, from control (C) and KD rats. Feeding rats a potassium deficient diet for 3-4 wk resulted in lower plasma [K+] (2.94 mEq/liter, KD vs. 4.47 C), and higher arterial pH (7.51 KD vs. 7.39 C). KD rats gained less weight than C but had higher renal cortical weight. Influx of 1 mM 22Na+ at 5 s (pHo 7.5, pHi 6.0, 10% CO2, 90% N2) into BLM vesicles was 44% higher in the KD group compared to C with no difference in equilibrium uptake. The increment in Na+ influx in the KD group was DIDS sensitive, suggesting that Na+:CO3=:HCO3- cotransport accounted for the observed differences. Kinetic analysis of Na+ influx showed a Km of 8.2 mM in KD vs. 7.6 mM in C and Vmax of 278 nmol/min/mg protein in KD vs. 177 nmol/min/mg protein in C. Influx of 1 mM 22Na+ at 5 s (pHo 7.5, pHi 6.0) into BBM vesicles was 34% higher in the KD group compared to C with no difference in equilibrium uptake. The increment in Na+ influx in the KD group was amiloride sensitive, suggesting that Na+/H+ exchange was responsible for the observed differences. Kinetic analysis of Na+ influx showed a Km of 6.2 mM in KD vs. 7.1 mM in C and Vmax of 209 nmol/min/mg protein in KD vs. 144 nmol/min/mg protein in C. Uptakes of Na(+)-dependent [3H]glucose into BBM and [14C]succinate into BLM vesicles were not different in KD and C groups, suggesting that the Na+/H+ exchanger and Na+:CO3=:HCO3- cotransporter activities were specifically altered in KD. We conclude that adaptive increases in basolateral Na+:CO3=:HCO3- cotransport and luminal Na+H+ exchange are likely responsible for increased HCO3- reabsorption in proximal tubules of KD animals. .A Soleimani M; Bergman JA; Hosford MA; McKinney TD. .I 275346 .U 91009811 .S J Clin Invest 9101; 86(4):1084-7 .M Amino Acid Sequence; Base Sequence; Female; Human; Hypoparathyroidism/*GE; Male; Molecular Sequence Data; Mutation/*; Parathyroid Hormones/*GE; Protein Precursors/*GE; Signal Peptides/*GE; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Mutation of the signal peptide-encoding region of the preproparathyroid hormone gene in familial isolated hypoparathyroidism. .P JOURNAL ARTICLE. .W Preproparathyroid hormone (preproPTH) gene mutation has been proposed as a cause of familial isolated hypoparathyroidism (FIH). We cloned the preproPTH alleles of a patient with autosomal dominant FIH and sequenced the coding regions, 5' flanking regions, and splice junctions. The putatively abnormal (based on previous linkage studies) allele differed from the other allele's normal sequence at only one nucleotide. This T to C point mutation changes the codon for position 18 of the 31 amino acid prepro sequence from cysteine to arginine, disrupting the hydrophobic core of the signal sequence. Because the hydrophobic core is required by secreted proteins for efficient translocation across the endoplasmic reticulum, the mutant protein is likely to be inefficiently processed. Indeed, in vitro studies demonstrated dramatically impaired processing of the mutant preproPTH to proPTH. In summary, we observed a point mutation in the signal peptide-encoding region of a preproPTH gene in one FIH kindred and demonstrated a functional defect caused by the mutation. Mutation of the signal sequence constitutes a novel pathophysiologic mechanism in man, and further study may yield important insights both into this form of hormone deficiency and into the role of signal sequences in human physiology. .A Arnold A; Horst SA; Gardella TJ; Baba H; Levine MA; Kronenberg HM. .I 275347 .U 91009812 .S J Clin Invest 9101; 86(4):1088-94 .M Animal; Antigenic Determinants; Autoantibodies/IM; Autoantigens/*AN/GE; Blotting, Northern; DNA/*IP; Epidermis/*IM; Female; Herpes Gestationis/*IM; Human; Pemphigoid, Bullous/*IM; Pregnancy; Rabbits; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Isolation of a human epidermal cDNA corresponding to the 180-kD autoantigen recognized by bullous pemphigoid and herpes gestationis sera. Immunolocalization of this protein to the hemidesmosome. .P JOURNAL ARTICLE. .W Autoantibodies present in the sera of patients with bullous pemphigoid (BP) bind to the basement membrane zone of normal human skin and commonly recognize two epidermal proteins, the BP240 and BP180 antigens. Two BP antigen cDNA clones from a lambda gt11 human keratinocyte library have been identified on the basis of reactivity with a BP serum. The fusion protein (FP) produced by one clone immunoadsorbed autoantibodies, which specifically recognized the BP180 by antigen, showing no cross-reactivity with BP240 by immunoblot analysis. The FP produced by the second clone immunoadsorbed autoantibodies which specifically reacted with the BP240 epidermal antigen. Northern blot analysis demonstrated that the BP180 and BP240 antigens are encoded by distinct RNA transcripts with lengths of 6.0 and 8.5 kb, respectively. Immunoblot analysis of the BP180 lysogen extract identified a 135-kD FP which was recognized by 7 of 16 BP sera and 7 of 8 herpes gestationis sera. A rabbit antiserum prepared against the lysogenic BP180 FP specifically recognized the BP180 antigen from human epidermal extracts by immunoblotting, labeled the BMZ by indirect immunofluorescence, and bound to human epidermal hemidesmosomes by immuno-electron microscopy. These results indicate that the BP180 antigen recognized by BP and herpes gestationis autoantibodies is a unique hemidesmosomal polypeptide, distinguishable from the BP240 antigen. .A Diaz LA; Ratrie H 3d; Saunders WS; Futamura S; Squiquera HL; Anhalt GJ; Giudice GJ. .I 275348 .U 91009815 .S J Clin Invest 9101; 86(4):1109-14 .M Cell Line; Human; HIV Infections/*IM; HIV-1/*PH; Interleukin-1/BI/*GE; Lipopolysaccharides/PD; Monocytes/ME/*MI; RNA/*AN; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tetradecanoylphorbol Acetate/PD. .T Modulation of interleukin-1 beta RNA in monocytic cells infected with human immunodeficiency virus-1. .P JOURNAL ARTICLE. .W The effect of HIV-1 infection on cytokine levels was studied in monocytic cells by using Northern blotting analysis. Monoblasts (THP-1, U937) did not express IL-1 beta RNA even if the cells were infected with HIV-1. After exposure to LPS (10 micrograms/ml) and 12-O-tetradecanoylphorbol-13-acetate (TPA, 100 nM) for 12 h, these HIV-1-infected monoblasts accumulated 8-15-fold greater levels of IL-1 beta RNA as compared with their HIV-1-uninfected counterparts that were similarly stimulated. In contrast, levels of RNAs coding for monocyte-colony-stimulating factor (M-CSF) and tumor necrosis factor-alpha (TNF alpha) were elevated less than twofold in the HIV-1-infected cells as compared with HIV-1-uninfected cells after their stimulation with LPS and TPA. Inhibition of new protein synthesis did not block the marked accumulation of IL-1 beta RNA produced by exposure to LPS and TPA in the HIV-1-infected cells. Time-course experiments showed that the maximal levels of IL-1 beta RNA occurred at 12 and 24 h after LPS and TPA stimulation of the HIV-1-infected and uninfected U937 cells, respectively. Studies of stability of RNA using actinomycin D showed that IL-1 beta RNA was equally stable in infected and uninfected U937 cells after their stimulation with TPA and LPS. Taken together, our data show that HIV-1 infection markedly augments IL-1 beta RNA accumulation in stimulated monocytic cells, probably through increasing rate of transcription of IL-1 beta. .A Yamato K; el-Hajjaoui Z; Simon K; Koeffler HP. .I 275349 .U 91009816 .S J Clin Invest 9101; 86(4):1115-23 .M Acute Disease; Animal; Fatty Acids, Essential/*DF; Female; Kidney/PA; Kidney Diseases/CI/*PC; Leukopenia/PP; Macrophages/PA; Methacrylates/PD; Nephrotic Syndrome/CI; Puromycin Aminonucleoside/*TO; Rats; Rats, Inbred Lew; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Thromboxane B2/UR. .T Essential fatty acid deficiency ameliorates acute renal dysfunction in the rat after the administration of the aminonucleoside of puromycin. .P JOURNAL ARTICLE. .W The administration of the aminonucleoside of puromycin (PAN) to rats causes the nephrotic syndrome that is associated with an acute decline in renal function, and an interstitial infiltrate. We examined whether essential fatty acid deficiency (EFAD), which inhibits macrophage infiltration in glomerulonephritis, affects PAN-induced renal dysfunction. Both control and EFAD rats developed proteinuria that resolved over 28 d. After PAN administration, there was a prominent infiltration of macrophages in rats fed a normal diet. The infiltrate was prevented by the EFAD diet. The absence of a macrophage interstitial infiltrate was associated with a significantly higher Cin in the EFAD rats than in controls at 7 d (5.21 +/- 1.19 versus 0.39 +/- 0.08, P less than 0.002 ml/min/kg BW). In addition, CPAH fell to less than 10 ml/min/kg BW by day 7 in controls, but remained the same as normal in the EFAD. After administration of PAN to control rats, there was no increase in urinary thromboxane excretion or an increase in glomerular thromboxane production. Furthermore, the effect of EFAD could not be mimicked by the administration of a thromboxane synthase inhibitor. Irradiation-induced leukopenia in rats on a normal diet markedly improved glomerular filtration and renal blood flow in acutely nephrotic rats. EFAD prevents the interstitial cellular infiltrate and the renal ischemia associated with experimental nephrosis. The recruitment of mononuclear cells into the kidney following PAN directly contributes to the decline in renal function. .A Harris KP; Lefkowith JB; Klahr S; Schreiner GF. .I 275350 .U 91009817 .S J Clin Invest 9101; 86(4):1124-36 .M Adult; Aged; Aged, 80 and over; Antigens, CD/*AN; Antigens, Differentiation, T-Lymphocyte/*AN/PH; Antigens, Surface/AN; Arthritis, Rheumatoid/*IM; Female; Human; Lymphocyte Transformation/*; Male; Middle Age; Receptors, Interleukin-2/AN; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Synovial Fluid/*IM; T-Lymphocytes/*IM; Tetradecanoylphorbol Acetate/PD. .T Activation pathways of synovial T lymphocytes. Expression and function of the UM4D4/CDw60 antigen. .P JOURNAL ARTICLE. .W Accumulating evidence implicates a central role for synovial T cells in the pathogenesis of rheumatoid arthritis, but the activation pathways that drive proliferation and effector function of these cells are not known. We have recently generated a novel monoclonal antibody against a rheumatoid synovial T cell line that recognizes an antigen termed UM4D4 (CDw60). This antigen is expressed on a minority of peripheral blood T cells, and represents the surface component of a distinct pathway of human T cell activation. The current studies were performed to examine the expression and function of UM4D4 on T cells obtained from synovial fluid and synovial membranes of patients with rheumatoid arthritis and other forms of inflammatory joint disease. The UM4D4 antigen is expressed at high surface density on about three-fourths of synovial fluid T cells and on a small subset of synovial fluid natural killer cells; in synovial tissue it is present on more than 90% of T cells in lymphoid aggregates, and on approximately 50% of T cells in stromal infiltrates In addition, UM4D4 is expressed in synovial tissue on a previously undescribed population of HLA-DR/DP-negative non-T cells with a dendritic morphology. Anti-UM4D4 was co-mitogenic for both RA and non-RA synovial fluid mononuclear cells, and induced IL-2 receptor expression. The UM4D4/CDw60 antigen may represent a functional activation pathway for synovial compartment T cells, which could play an important role in the pathogenesis of inflammatory arthritis. .A Fox DA; Millard JA; Kan L; Zeldes WS; Davis W; Higgs J; Emmrich F; Kinne RW. .I 275351 .U 91009818 .S J Clin Invest 9101; 86(4):1137-41 .M Base Sequence; DNA/AN; Gaucher's Disease/EN/*GE; Glucosylceramidase/*GE; Human; Mutation; Polymerase Chain Reaction; Pseudogenes/*; RNA/AN; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Transcription, Genetic/*. .T High level transcription of the glucocerebrosidase pseudogene in normal subjects and patients with Gaucher disease. .P JOURNAL ARTICLE. .W Gaucher disease is due to mutations involving the glucocerebrosidase gene. A closely homologous pseudogene is located approximately 16 kD downstream from the functional gene. Sequence analysis of clones from cDNA libraries made from skin fibroblast cultures showed several independent clones with the sequence of an aberrantly processed pseudogene message. Examination of cellular RNA from lymphoblasts or fibroblasts obtained from thirteen Gaucher disease patients, one Gaucher disease heterozygote, and four normal subjects showed that the pseudogene was consistently transcribed, and that in some cases the level of transcription seemed to be approximately equal to that of the functional gene. The transcription of the pseudogene must be taken into account when attempting to detect mutations of glucocerebrosidase by the study of cDNA libraries. .A Sorge J; Gross E; West C; Beutler E. .I 275352 .U 91009820 .S J Clin Invest 9101; 86(4):1151-7 .M Alleles; Base Sequence; Chromosome Deletion/*; Human; Introns/*; Meningeal Neoplasms/*GE; Meningioma/*GE; Molecular Sequence Data; Platelet-Derived Growth Factor/*GE; Polymerase Chain Reaction; Proto-Oncogene Proteins/*GE; Proto-Oncogenes/*; Repetitive Sequences, Nucleic Acid/*; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Deletion of Alu sequences in the fifth c-sis intron in individuals with meningiomas. .P JOURNAL ARTICLE. .W An abnormality in the c-sis protooncogene was identified in leukocyte DNA from members of a family predisposed to the development of meningioma, and was found to be associated with the development of the tumor in those individuals. Molecular analysis of this abnormality demonstrated a deletion within the fifth intron of the c-sis gene. The normal c-sis gene has an Alu sequence in this region which includes two perfect 130 nucleotide repeated sequences separated by 5 bp. The deleted c-sis allele is missing precisely one copy of the 130 bp repeat and the intervening 5 bp. An identical deletion was also found in DNA from 1 of 13 sporadic meningiomas. .A Smidt M; Kirsch I; Ratner L. .I 275353 .U 91009821 .S J Clin Invest 9101; 86(4):1158-63 .M Base Sequence; Child; Complement 3/AN/*DF/GE; DNA/AN; Exons; Female; Human; Male; Mutation; Polymerase Chain Reaction; RNA Splicing; Support, Non-U.S. Gov't. .T Molecular basis of hereditary C3 deficiency. .P JOURNAL ARTICLE. .W Hereditary deficiency of complement component C3 in a 10-yr-old boy was studied. C3 could not be detected by RIA of serum from the patient. Segregation of C3 S and C3 F allotypes within the family confirmed the presence of a null gene for C3, for which the patient was homozygous. 30 exons have been characterized, spanning the entire beta chain of C3 and the alpha chain as far as the C3d region. Sequence analysis of the exons derived from the C3 null gene showed no abnormalities in the coding sequences. A GT-AT mutation at the 5' donor splice site of the intervening sequence 18 was found in the C3 null gene. Exons 17-21 were amplified by the polymerase chain reaction (PCR) from first-strand cDNA synthesized from mRNA obtained from peripheral blood monocytes stimulated with LPS. This revealed a 61-bp deletion in exon 18, resulting from splicing of a cryptic 5' donor splice site in exon 18 with the normal 3' splice site in exon 19. This deletion leads to a disturbance of the reading frame of the mRNA with a stop codon 17 bp downstream from the abnormal splice in exon 18. His parents had both the normal and abnormal C3 mRNA and were shown to be heterozygous for this mutation by sequence analysis of genomic DNA amplified by PCR. Similar splice mutants have previously been reported in the beta-globin, phenylalanine hydroxylase, and porphobilinogen deaminase genes. This mutation is sufficient to cause the deficiency of C3 in the patient. .A Botto M; Fong KY; So AK; Rudge A; Walport MJ. .I 275354 .U 91009823 .S J Clin Invest 9101; 86(4):1172-8 .M Animal; Biological Transport/DE; Body Water/ME; Epithelium/ME; Kidney Medulla/*ME; Kidney Tubules, Collecting/*ME; Permeability; Phloretin/PD; Rats; Rats, Inbred Strains; Support, U.S. Gov't, P.H.S.; Urea/*ME. .T Apical membrane limits urea permeation across the rat inner medullary collecting duct. .P JOURNAL ARTICLE. .W Urea diffuses across the terminal inner medullary collecting duct (IMCD) via a facilitated transport pathway. To examine the mechanism of transcellular urea transport, membrane-apparent urea (Purea) and osmotic water (Pf) permeabilities of IMCD cells were measured by quantitative light microscopy in isolated IMCD-2 tubules perfused in the absence of vasopressin. Basolateral membrane Pf, determined by addition of raffinose to the bath, was 69 microns/s. Basolateral membrane Purea, determined by substituting urea for raffinose without change in osmolality, was 14 X 10(-5) cm/s. Bath phloretin inhibited basolateral Purea by 85% without a significant effect on Pf. The basolateral reflection coefficient for urea, determined by addition of urea in the presence of phloretin, was 1.0. These results indicate that urea crosses the basolateral membrane by diffusion, and not by solvent drag. In perfused tubules, the rate of cell swelling following substitution of urea for mannitol was significantly greater with bath than lumen changes. After correcting for membrane surface area, the basolateral membrane was twofold more permeable than the apical membrane. Conclusions: (a) in the absence of vasopressin, urea permeation across the IMCD cell is limited by the apical membrane; (b) the basolateral membrane contains a phloretin-sensitive urea transporter; (c) transepithelial urea transport occurs by movement of urea through the IMCD cell. .A Star RA. .I 275355 .U 91009824 .S J Clin Invest 9101; 86(4):1179-92 .M Ammonia/ME; Animal; Antioxidants/*; Bicarbonates/PD; Growth; Hemodynamics; Iron/AN; Kidney/*GD/PA/PH; Lipid Peroxidation; Male; Muscles/ME; Nephrons/PH; Organ Weight; Ornithine Decarboxylase/AN; Potassium/ME; Proteinuria/ET; Rats; Rats, Inbred Strains; Selenium/*DF; Support, U.S. Gov't, P.H.S.; Vitamin E Deficiency/*PP. .T Induction of renal growth and injury in the intact rat kidney by dietary deficiency of antioxidants. .P JOURNAL ARTICLE. .W We report induction of renal growth and injury in the intact rat kidney using a diet deficient in vitamin E and selenium. This diet was imposed in 3-wk-old male weanling rats, and after 9 wk, enhancement of growth, characterized by increased wet weight, dry weight, protein content, and DNA content appeared. Morphometric analyses revealed increased kidney volume, tubular epithelial volume, and mean glomerular volume. There were no differences in nephron number. The animals on the deficient diet displayed increased urinary protein excretion at 9 wk. Renal injury was also characterized by an interstitial cellular infiltrate and diminutions in glomerular filtration rate. Enhanced growth and injury were antedated by increased renal ammoniagenesis. The deficient diet did not induce metabolic acidosis, potassium depletion, glucose intolerance, or elevated plasma amino acid concentration. Enhancement of renal growth and ammoniagenesis by the deficient diet was not suppressible by chronic alkali therapy. Stimulation of renal growth could not be ascribed to increased intrarenal iron, induction of ornithine decarboxylase, or alterations in glomerular hemodynamics. Stimulation of renal ammoniagenesis by dietary deficiency of antioxidants is a novel finding, as is induction of growth and injury. We suggest that increased renal ammoniagenesis contributes to induction of renal growth and injury. .A Nath KA; Salahudeen AK. .I 275356 .U 91009825 .S J Clin Invest 9101; 86(4):1193-203 .M Amino Acid Sequence; Animal; Arthritis, Infectious/*IM; Autoantibodies/*AN/IM; Cross Reactions; Female; Human; HLA-B27 Antigen/*IM; Male; Mice; Molecular Sequence Data; Plasmids/*; Rabbits; Shigella flexneri/*GE; Spondylitis, Ankylosing/ET; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Autoantibodies to the HLA-B27 sequence cross-react with the hypothetical peptide from the arthritis-associated Shigella plasmid. .P JOURNAL ARTICLE. .W We previously reported elevated serum antibody levels to a peptide representing the HLA-B27 polymorphic region (B27 peptide) in HLA-B27(+) ankylosing spondylitis (AS) patients. A plasmid (pHS-2) isolated from arthritogenic Shigella flexneri strains had been shown to encode an amino acid sequence homologous to HLA-B27. Rabbit antibody to this sequence (pHS-2 peptide) strongly cross-reacted with B27 peptide and, to a much lesser extent, with Klebsiella nitrogenase peptide. Serum antibody levels to pHS-2 peptide were studied in 160 spondylarthropathy patients. 12 of 115 (10.4%) AS patients, 2 of 45 (4.4%) patients with Reiter's syndrome or reactive arthritis as well as 6 of 147 (4.1%) normal controls were shown to have elevated anti-pHS-2 peptide antibodies. Antibody levels to B27 and pHS-2 peptides were significantly correlated in 134 HLA-B27(+) patients (r = 0.333, P less than 0.001). 13 of 15 affinity-purified anti-B27 peptide antibodies from patients strongly cross-reacted with pHS-2 peptide, whereas only 3 weakly cross-reacted to nitrogenase peptide. Leucine appeared to be a critical residue for this cross-reaction. AS patients' anti-B27 peptide antibodies reacted with HLA-B27 transfected L cells. These results may suggest that pHS-2 peptide more efficiently "mimics" B27 peptide than does nitrogenase peptide. Involvement of pHS-2 in pathogenesis of spondylarthropathy through molecular mimicry mechanisms requires further study. .A Tsuchiya N; Husby G; Williams RC Jr; Stieglitz H; Lipsky PE; Inman RD. .I 275357 .U 91009828 .S J Clin Invest 9101; 86(4):1222-33 .M Adenosine Cyclic Monophosphate/AN; Animal; Anoxia/*PP; Coronary Disease/ME; Energy Metabolism; Glucose/*ME/PD; Glycogen/ME; Glycolysis/*; Heart/DE/*PP; Insulin/PD; Potassium/ME; Rabbits. .T Enhanced utilization of exogenous glucose improves cardiac function in hypoxic rabbit ventricle without increasing total glycolytic flux. .P JOURNAL ARTICLE. .W The effects of elevated glucose on cardiac function during hypoxia were investigated in isolated arterially perfused rabbit interventricular septa. Rest tension, developed tension, intracellular potential, 42K+ efflux, lactate production, exogenous glucose utilization, and tissue high-energy phosphate levels were measured during a 50-min period of hypoxia with 4, 5, or 50 mM glucose present (isosmotically balanced with sucrose) and during reoxygenation for 60 min with perfusate containing 5 mM glucose/45 mM sucrose. At physiologic (4 or 5 mM) and supraphysiologic glucose (50 mM), lactate production and high-energy phosphate levels during hypoxia were equally well maintained, yet cardiac dysfunction was markedly attenuated by 50 mM glucose. Despite identical rates of total glycolytic flux, exogenous glucose utilization was enhanced by 50 mM glucose so that tissue glycogen levels remained normal during hypoxia, whereas glycogen became depleted with 4 or 5 mM glucose present during hypoxia. Most of the beneficial effects of 50 mM glucose occurred during the first 25 min of hypoxia. Prior glycogen depletion had no deleterious effects during hypoxia with 50 mM glucose present, but exacerbated cardiac dysfunction during hypoxia with 5 mM glucose present. These findings indicate that enhanced utilization of exogenous glucose improved cardiac function during hypoxia without increasing total glycolytic flux or tissue high-energy phosphate levels, suggesting a novel cardioprotective mechanism. .A Runnman EM; Lamp ST; Weiss JN. .I 275358 .U 91009831 .S J Clin Invest 9101; 86(4):1249-54 .M Animal; Autoantibodies/BI; Autoimmune Diseases/*ET/IM; B-Lymphocytes/*IM; DNA/IM; Immunoglobulins/AN; Lupus Nephritis/*ET/IM; Lymphocyte Transformation/*; Mice; Mice, Inbred Strains; Ovalbumin/IM. .T Polyclonal B cell activation in lupus-prone mice precedes and predicts the development of autoimmune disease. .P JOURNAL ARTICLE. .W Polyclonal B cell activation is an early feature of autoimmune disease in humans and mice with systemic lupus erythematosus. The contribution of polyclonal activation to the progression of autoimmunity is unclear, however, since it precedes the development of end-organ damage by months or years. To examine this issue, 109 autoimmune-prone (NZB X NZW)F1 X NZB backcross mice were hemi-splenectomized at 10 wk and the number and antigenic specificity of their Ig-secreting B cells quantitated by ELISA spot assay. Of the 61 mice that had polyclonally increased numbers of Ig-secreting cells/spleen, 31 died by 6 mo. In contrast, 0/48 backcross mice with normal numbers of Ig-secreting B cells at 10 wk died over the same period (P less than 0.001). Polyclonally activated mice also developed proteinuria earlier and more frequently than littermates with normal numbers of Ig-secreting cells (P less than 0.001). As adults, backcross mice with proteinuria expressed repertoires skewed towards the production of anti-DNA antibodies. At 10 wk these same mice expressed repertoires marked by polyclonal activation rather than preferential anti-DNA production. These findings indicate that autoimmune disease in SLE is accompanied by the autoantigen-driven production of autoantibodies but is preceded and predicted by polyclonal B cell activation. .A Klinman DM. .I 275359 .U 91009833 .S J Clin Invest 9101; 86(4):1261-9 .M Cells, Cultured; Colony-Stimulating Factors/GE; Cytokines/*GE; Gene Expression Regulation/*; Genes, ras/*; Human; Interleukin-1/GE; Interleukin-6/GE; Mutation; Repetitive Sequences, Nucleic Acid; RNA, Messenger/AN; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Transcription, Genetic/*. .T Expression of ras oncogenes in cultured human cells alters the transcriptional and posttranscriptional regulation of cytokine genes. .P JOURNAL ARTICLE. .W Autonomous production of cytokines such as the hematopoietic colony-stimulating factors (CSFs), IL-1, or IL-6 has been demonstrated in numerous human and murine neoplasms, and may be involved in the pathogenesis of several paraneoplastic syndromes such as leukocytosis, fever, and hypercalcemia. Because of the high frequency with which mutations in ras protooncogenes have been detected in human tumors, as well as evidence linking ras gene products to activation of certain cellular functions, we investigated whether ras mutations might influence the regulation of cytokine genes. Normal human fibroblasts transfected with a mutant val12 H-ras oncogene expressed increased levels of mRNA transcripts encoding granulocyte-CSF (G-CSF), granulocyte-macrophage-CSF (GM-CSF), and IL-1 beta compared with controls. Human mesothelioma cells transfected with a mutant asp12 N-ras oncogene exhibited similar alterations in cytokine gene expression. Estimates of transcriptional activity by nuclear run-on analysis revealed a selective increase in transcription only for the IL-1 gene. Analysis of mRNA half-life demonstrated a marked increase in the stability of numerous cytokine transcripts, including G-CSF, GM-CSF, IL-1, and IL-6. The addition of anti-IL-1 neutralizing antibody to cultures of cells expressing ras mutants did not block the expression of any of the cytokines examined, suggesting that the baseline expression of GM-CSF, G-CSF, and IL-6 was not a secondary event due to the increased transcription of IL-1. These results indicate that mutations in ras genes may alter expression of several cytokine genes through both transcriptional and posttranscriptional mechanisms. .A Demetri GD; Ernst TJ; Pratt ES 2d; Zenzie BW; Rheinwald JG; Griffin JD. .I 275360 .U 91009834 .S J Clin Invest 9101; 86(4):1270-7 .M Animal; DNA/AN; Extravascular Lung Water/*PH; Female; Fetal Organ Maturity; Lung/AB/*EM; Lung Volume Measurements; Organ Weight; Phosphatidylcholines/AN; Pregnancy; Sheep. .T Role of lung fluid volume in growth and maturation of the fetal sheep lung. .P JOURNAL ARTICLE. .W We studied the effects of alterations in lung fluid volume on growth and maturation of the fetal lung. In a chronic fetal sheep preparation, right fetal lung volume was decreased by drainage of lung fluid while the volume of the left lung was expanded by mainstem bronchus ligation leading to lung fluid retention. After an experimental period of 25 d (from 105 to 129 d of gestation, term = 145 d), the right (deflated) lung was significantly hypoplastic and contained less DNA than the controls; 175.15 +/- 55.18 vs. 346.77 +/- 61.97 mg, respectively; P less than 0.001. In contrast, the left (expanded) lung was significantly hyperplastic and contained more DNA than the controls; 390.74 +/- 103.53 vs. 238.85 +/- 33.32 mg, respectively; P = 0.001. Biochemical indices of lung maturation, including total phospholipids, phosphatidylcholine, and disaturated phosphatidylcholine content expressed per unit of tissue DNA, were no different when comparing the hypoplastic, hyperplastic, and control lungs. These findings demonstrate that fetal lung cell multiplication is influenced by local distension with lung fluid, while the biochemical maturation of fetal lung surfactant is under systemic control. .A Moessinger AC; Harding R; Adamson TM; Singh M; Kiu GT. .I 275361 .U 91009835 .S J Clin Invest 9101; 86(4):1278-84 .M Animal; Arteries/*PH; Calcium/ME; Cardiac Pacing, Artificial; Dobutamine/*PD; Dogs; Female; Heart Rate/*/DE; Male; Myocardial Contraction/*/DE; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Vascular Resistance. .T Role of ventriculovascular coupling in cardiac response to increased contractility in closed-chest dogs [published erratum appears in J Clin Invest 1991 Feb;87(2):755] .P JOURNAL ARTICLE. .W While both dobutamine and pacing tachycardia augment left ventricular (LV) contractility, whether overall cardiovascular response to these stimuli is comparable is not known. To address this question we studied seven dogs previously instrumented with three LV diameter gauges and LV pressure manometers. After ganglionic blockade and sedation, caval occlusions were performed at heart rates of 120, 160, and 200 bpm before (C), and 160 and 200 bpm after administration of 10 micrograms/kg per min dobutamine, i.v. (D). The effective arterial elastance (Ea) went up from 14.2 +/- 4.5 mmHg/ml at C120 to 19.6 +/- 8.8 (P less than 0.025 vs C120) and 24.2 +/- 10.4 (P less than 0.001 vs C120) mmHg/ml at C160 and C200. Ees, the slope of the end-systolic pressure-volume relation, increased with pacing from 9.7 +/- 4.6 to 11.7 +/- 4.3 (P less than 0.02), and 13.2 +/- 5.7 (P less than 0.02) mmHg/ml at 160 and 200 bpm. With dobutamine infusion Ea went down, and Ees was further increased to 37.0 +/- 20.9 mmHg/ml at 160 bpm (P less than 0.002 vs C160), and 53.0 +/- 22.6 mmHg/ml at 200 bpm (P less than 0.002 vs C200). Comparison of stroke work and pressure-volume area from single beats with matched LV end-diastolic volumes showed that these were both increased by dobutamine, but not by pacing tachycardia. While increased heart rate after dobutamine markedly increased contractility, Ea was not changed, and neither stroke work nor pressure-volume was further increased. Thus, how well an increase in contractility is transmitted to the periphery is determined in part by arterial behavior. Assessment of both the arterial system and cardiac contractility is necessary to fully evaluate the overall impact of an inotropic stimulus. .A Freeman GL; Colston JT. .I 275362 .U 91009837 .S J Clin Invest 9101; 86(4):1293-300 .M Adult; Cell Adhesion Molecules, Neuronal/*AN/IM; Child; Female; Fetal Heart/*CH; Heart/IR; Heart Transplantation/*; Human; Immunoblotting; Immunohistochemistry; Myocardium/*CH; Pregnancy; Support, Non-U.S. Gov't; Transplantation, Homologous. .T Myocardial localization and isoforms of neural cell adhesion molecule (N-CAM) in the developing and transplanted human heart. .P JOURNAL ARTICLE. .W Neural cell adhesion molecule (N-CAM) has been implicated in cellular interactions involved in cardiac morphogenesis and innervation. Immunohistochemical techniques and Western blot analysis were used to determine the localization and isoforms of N-CAM in the developing and extrinsically denervated human heart. Myocardial and conducting cells in the fetal heart (7-24 wk gestation) exhibited sarcolemmal immunoreactivity, the major desialo N-CAM isoforms being 150, 145, 120, 115, and 110 kD. N-CAM expression appeared to be downregulated in the myocardium during adult life, with relatively little sarcolemmal immunoreactivity being detected in normal donor tissues. In contrast to the temporal changes observed in the myocardium, both the developing and mature cardiac innervation displayed N-CAM immunofluorescence staining, localized to neuronal cell bodies, nerve fascicles and fibres. Extrinsically denervated cardiac allografts, obtained 2 d to 91 mo after transplantation, showed extensive sarcolemmal and intercalated disc immunostaining and expression of 125-, 120-, and 115-kD isoforms. Tissues from explanted recipient hearts and atrial appendage samples obtained during coronary bypass graft operations were also examined and displayed varying amounts of N-CAM immunoreactivity. We conclude that the expression of N-CAM immunoreactivity and isoforms in the human heart is developmentally regulated and may be modulated by factors such as cardiac innervation and myocardial hypertrophy. .A Gordon L; Wharton J; Moore SE; Walsh FS; Moscoso JG; Penketh R; Wallwork J; Taylor KM; Yacoub MH; Polak JM. .I 275363 .U 91009838 .S J Clin Invest 9101; 86(4):1301-5 .M Amino Acid Sequence; Antigens, Surface/*AN/PH; Autoantigens/*AN; Cell Membrane/IM; DNA-Binding Proteins/*AN/PH; Hela Cells/IM; Human; Molecular Sequence Data. .T Cell surface expression of the 70-kD component of Ku, a DNA-binding nuclear autoantigen. .P JOURNAL ARTICLE. .W The Ku complex, a heterodimer of 86- and 70-kD proteins, is a nuclear DNA-binding autoantigen. However, hydrophobicity analysis of the deduced amino acid sequence of the 70-kD protein had strongly suggested that this might also be a membrane protein. In the present study, using antibodies to synthetic peptides and a polyclonal antiserum to the purified protein, we show that the 70-kD protein of the Ku complex is present in isolated plasma membranes of human cells. By indirect immunofluorescence microscopy and fluorescein-activated cell sorting, we demonstrate that this autoantigen is exposed on the cell surface. In addition, we have identified several domains of the protein that are exposed. Our study provides one of the first demonstrations of a eukaryotic, nuclear DNA-binding protein that is also on the cell membrane. Moreover, our results might help explain how autoantibodies to the Ku autoantigen could target cells for an autoimmune attack. .A Prabhakar BS; Allaway GP; Srinivasappa J; Notkins AL. .I 275364 .U 91009839 .S J Clin Invest 9101; 86(4):1306-12 .M Adolescence; Adult; Cells, Cultured; Chylomicrons/*ME; Female; Homozygote; Human; Hypercholesterolemia, Familial/*ME; Lipoproteins, LDL/ME; Lipoproteins, VLDL/ME; Male; Metabolic Clearance Rate; Receptors, LDL/*PH; Support, Non-U.S. Gov't; Vitamin A/AA/ME. .T Chylomicron remnant clearance from the plasma is normal in familial hypercholesterolemic homozygotes with defined receptor defects. .P JOURNAL ARTICLE. .W The retinyl palmitate fat tolerance test was used to measure chylomicron remnant clearance in 10 normal subjects (apolipoprotein E [apo E] isotypes 3 or 4 only), 6 normolipidemic apo E2/2 homozygotes and 5 familial hypercholesterolemic homozygotes. Skin fibroblasts with fully upregulated LDL receptors from the latter subjects degraded rabbit 125I-beta VLDL in vitro at rates ranging from less than 10-48% of normal. Experiments in vivo revealed no significant differences between the normal and homozygous familial hypercholesterolemic (FHH) subjects in chylomicron remnant clearance assessed on the basis of "areas under the curves" for retinyl palmitate levels present in post-prandial serum, chylomicron remnants (Sf. less than 1,000), or chylomicrons (Sf. greater than 1,000). Remnant clearance was greatly decreased at all times in the apo E2/2 homozygotes, indicative of an important degree of flux control exerted by a receptor-mediated step involving apo E as ligand. The absence of any excess remnant accumulation in FHH subjects with varying "impairment" of LDL receptor-mediated degradation of apo E-containing lipoproteins, permits the conclusion that chylomicron remnants are initially cleared from the plasma by apo E-recognizing receptors which are genetically distinct from LDL receptors. .A Rubinsztein DC; Cohen JC; Berger GM; van der Westhuyzen DR; Coetzee GA; Gevers W. .I 275365 .U 91009840 .S J Clin Invest 9101; 86(4):1313-9 .M Animal; Calcitriol/BL/PD; Cell Count; Flow Cytometry; Gene Expression Regulation/*; Hypercalcemia/*ME; Hypocalcemia/*ME; Male; Parathyroid Glands/CY; Parathyroid Hormones/*GE; Rats; RNA, Messenger/AN; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Vitamin D Deficiency/*ME. .T Regulation of parathyroid hormone gene expression by hypocalcemia, hypercalcemia, and vitamin D in the rat. .P JOURNAL ARTICLE. .W In vivo in the rat 1,25(OH)2D3 decreases and a low calcium increases PTH mRNA levels. We now report the effect of 3 and 8 wk of changes in dietary vitamin D and calcium on PTH mRNA levels. PTH mRNA levels were increased by 3 wk of calcium deficiency (five times), a vitamin D-deficient diet (two times), and combined deficiency (10 times), but not changed by high calcium. Vitamin D-deficient-diet rats' PTH mRNA did not decrease after a single large dose of 1,25(OH)2D3, but did decrease partially after repeated daily doses of 1,25(OH)2D3. Rats after a vitamin D-, calcium-deficient (-D-Ca) diet did not respond to changes in serum calcium at 1 h. Flow cytometry of isolated cells from parathyroid-thyroid tissue separated the smaller parathyroid from the larger thyroid cells and allowed an analysis of parathyroid cell number. In normal vitamin D/normal calcium (NDNCa) rats the parathyroid cells were 24.7 +/- 3.4% (n = 6) of the total cell number, whereas in -D-Ca rats they were 41.8 +/- 6.6% (n = 6) (P less than 0.05). That is, -D-Ca rats had 1.7 times the number of cells, whereas they had 10 times the amount of PTH mRNA, indicating the major contribution (6 times) of increased PTH gene expression per cell. Moreover, a calcium-deficient, more so than a vitamin D-deficient diet, amplifies the expression of the PTH gene, and vitamin D is necessary for an intact response of PTH mRNA to 1,25(OH)2D3 or calcium. .A Naveh-Many T; Silver J. .I 275366 .U 91009844 .S J Clin Invest 9101; 86(4):1343-6 .M Adult; Chromosome Deletion; DNA/AN; DNA Insertion Elements; Female; Genotype; Human; Kininase II/BL/*GE; Male; Middle Age; Polymorphism (Genetics)/*; Restriction Fragment Length Polymorphisms; Support, Non-U.S. Gov't. .T An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. .P JOURNAL ARTICLE. .W A polymorphism consisting of the presence or absence of a 250-bp DNA fragment was detected within the angiotensin I-converting enzyme gene (ACE) using the endothelial ACE cDNA probe. This polymorphism was used as a marker genotype in a study involving 80 healthy subjects, whose serum ACE levels were concomitantly measured. Allele frequencies were 0.6 for the shorter allele and 0.4 for the longer allele. A marked difference in serum ACE levels was observed between subjects in each of the three ACE genotype classes. Serum immunoreactive ACE concentrations were, respectively, 299.3 +/- 49, 392.6 +/- 66.8, and 494.1 +/- 88.3 micrograms/liter, for homozygotes with the longer allele (n = 14), and heterozygotes (n = 37) and homozygotes (n = 29) with the shorter allele. The insertion/deletion polymorphism accounted for 47% of the total phenotypic variance of serum ACE, showing that the ACE gene locus is the major locus that determines serum ACE concentration. Concomitant determination of the ACE genotype will improve discrimination between normal and abnormal serum ACE values by allowing comparison with a more appropriate reference interval. .A Rigat B; Hubert C; Alhenc-Gelas F; Cambien F; Corvol P; Soubrier F. .I 275367 .U 91009845 .S J Clin Invest 9101; 86(4):1347-51 .M Adolescence; Adult; Antibodies, Monoclonal/*IM; Antigens, Differentiation, T-Lymphocyte/*PH; Bone Marrow Transplantation/*; Calcium/*ME; Female; Graft vs Host Disease/ME; Human; Lymphocyte Transformation; Male; Middle Age; Receptors, Antigen, T-Cell/*PH; Support, Non-U.S. Gov't; T-Lymphocytes/*ME. .T Failure of T cell receptor-anti-CD3 monoclonal antibody interaction in T cells from marrow recipients to induce increases in intracellular ionized calcium. .P JOURNAL ARTICLE. .W There are multiple immune defects in T cells from recipients after bone marrow transplantation (BMT). This study examines recipient T cells for increases in intracellular ionized calcium concentration [( Ca2+]i) after binding the T cell receptor-CD3 complex with anti-CD3 MAb. PBL from 10 of 23 short-term recipients (less than 1 yr after BMT) responded poorly (less than 35% of control) to anti-CD3 stimulation and PBL from 9 of 23 had blunted calcium flux responses (35-70% of control). Purified CD2+, CD56- cells from seven additional short-term recipients including three autologous marrow recipients were closely examined, and a sizable proportion of CD3+ cells from six of seven recipients did not increase [Ca2+]i after anti-CD3 stimulation. The decreased magnitude of the responses was due to decreased numbers of responding cells and not to a decrease in mean CD3 fluorescent intensity or in calcium flux responses on a single cell basis. Five of seven long-term recipients (greater than 1 yr after BMT) had PBL that responded normally and two of seven had PBL with blunted calcium flux responses. The data show that the signal transduction response mediated by the CD3-antigen receptor as measured by calcium flux is defective early after autologus or allogeneic BMT. .A Yamagami M; McFadden PW; Koethe SM; Ratanatharathorn V; Lum LG. .I 275368 .U 91009846 .S J Clin Invest 9101; 86(4):1352-7 .M Angiotensin II/*AN/IM; Angiotensin III/*AN/IM; Animal; Kidney/*CH; Kidney Glomerulus/CH; Kidney Tubules/CH; Male; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Endogenous angiotensin concentrations in specific intrarenal fluid compartments of the rat. .P JOURNAL ARTICLE. .W To examine angiotensin (ANG) concentrations in fluid compartments near known intrarenal ANG receptors, we measured ANG concentrations in glomerular filtrate (GF), star vessel plasma (SVP), and luminal fluid from the early, mid, and late proximal tubule (E, M, and L PT). Samples were collected from euvolemic Munich-Wistar rats by free-flow micropuncture; ANG concentrations were measured by RIA. In one group of rats, concentrations of total immunoreactive ANG (reflecting ANG II and lesser amounts of three fragments) in GF and E, M, and L PT fluid averaged 29-40 nM compared with 32 pM in systemic plasma. In a second group, immunoreactive ANG concentrations in SVP also exceeded systemic levels by a factor of 1,000. In a final group, samples of GF and LPT fluid were purified by HPLC before RIA to measure ANG II and III concentrations specifically: their respective concentrations were 6-8 nM and 14-25 nM. We interpret these results to indicate that substantial amounts of ANG peptides are released into or generated within intrarenal fluid compartments, in which local ANG is likely to effect regulation of renal function independently of systemic ANG. .A Seikaly MG; Arant BS Jr; Seney FD Jr. .I 275369 .U 91009847 .S J Clin Invest 9101; 86(4):1358-63 .M Acute Disease; Adolescence; Adult; DNA, Viral/AN; Epstein-Barr Virus/GE; Gene Rearrangement, T-Lymphocyte/*; Genotype; Human; Infectious Mononucleosis/GE/*IM; Male; Phenotype; T-Lymphocytes/*IM. .T Oligoclonal T cell receptor gene rearrangements in blood lymphocytes of patients with acute Epstein-Barr virus-induced infectious mononucleosis. .P JOURNAL ARTICLE. .W Gene rearrangement studies were performed on blood lymphocytes from eight patients with acute Epstein-Barr virus-induced infectious mononucleosis. The diagnosis in each case was based on characteristic clinical, hematologic, and serologic findings. The blood lymphocytes in each patient consisted predominantly of CD8+ T cells. EBV DNA was detected in seven patients by Southern blot analysis (EBV Bam HI W probe, Bam HI). A germline configuration was found for the immunoglobulin heavy and light chain genes (JH probe, Bam HI and Eco RI; C kappa probe, Bam HI; and C lambda probe, Eco RI). T cell receptor gene rearrangements were detected with J gamma and J beta 1 + 2 probes. Using a J gamma probe with two different restriction enzymes (Bgl II and Eco RI), the blood from each patient showed several bands corresponding to the polyclonal pattern previously described in the blood of normal individuals. Using J beta 1 + 2 probes with two different restriction enzymes (Bgl II and Bam HI), each case showed from 3 to about 12 extragermline bands of varying intensity and in different locations from case to case. In addition, each case showed relative deletion of the J beta 1 germline band. This oligoclonal pattern of T cell receptor gene rearrangements has not been previously reported in benign or malignant T cell populations. .A Strickler JG; Movahed LA; Gajl-Peczalska KJ; Horwitz CA; Brunning RD; Weiss LM. .I 275370 .U 91009848 .S J Clin Invest 9101; 86(4):1364-8 .M Animal; Cytoplasmic Granules/*ME; Fibrinogen/*BI/GE; IgG/*BI/GE; Megakaryocytes/*ME; Mice; Polymerase Chain Reaction; Rats; RNA, Messenger/AN; Serum Albumin/*BI/GE; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Platelet alpha-granule fibrinogen, albumin, and immunoglobulin G are not synthesized by rat and mouse megakaryocytes. .P JOURNAL ARTICLE. .W It has been assumed that endogenous synthesis by the platelet precursor cell, the bone marrow megakaryocyte, is the major source of platelet alpha-granule protein. To test this hypothesis, we used mRNA phenotyping to detect in megakaryocytes the presence of mRNA transcripts specific for various proteins. Our results indicate that megakaryocytes synthesize platelet factor 4, a protein relatively specific for platelets, but do not express mRNA transcripts for the fibrinogen, albumin, or IgG found in alpha-granules. We have previously shown that megakaryocytes endocytose circulating proteins, including fibrinogen, albumin, and IgG, and incorporate them into alpha-granules. Thus, platelets appear to contain a unique type of secretory granule whose contents originate by both endogenous synthesis and endocytosis from plasma. Under basal conditions, the source of alpha-granule fibrinogen is plasma. .A Handagama P; Rappolee DA; Werb Z; Levin J; Bainton DF. .I 275371 .U 91009907 .S J Clin Pathol 9101; 43(9):701-2 .M Europe; Human; Microbiology/*; Pathology, Clinical/*. .T Pathology across Europe: differences and similarities. 2. Microbiology. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .A Banatvala JE. .I 275372 .U 91009908 .S J Clin Pathol 9101; 43(9):703-9 .M Hemostasis; Human; Thrombosis/*/ET/GE/TH. .T Guidelines on the investigation and management of thrombophilia. The British Committee for Standards in Haematology. .P GUIDELINE; JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .I 275373 .U 91009909 .S J Clin Pathol 9101; 43(9):712-3 .M England; Hospitals, Military/ST; Human; Laboratories/ST; Medical Audit/*; Specimen Handling/*ST; Transportation. .T Specimen transport audit. .P JOURNAL ARTICLE. .W A specimen transport audit was performed at a routine and reference laboratory. Over the survey period (1986-89) the percentage of specimens received and assessed as hazardous (inadequately packed, misidentified, or contaminated by leakage) fell significantly from 12.0 to 2.8%. Specimen transport audit identified technical and logistical faults associated with sample transmission. It is concluded that no type of hazard should exceed 0.5% of samples, with the total being less than 1% of specimens received. Specimen transport audit is an additional laboratory performance indicator. .A Garner P; Masterton RG. .I 275374 .U 91009910 .S J Clin Pathol 9101; 43(9):714-8 .M Acid Phosphatase/AN; Aged; Female; Human; Lymphoma, B-Cell/EN/EP/*PA; Lymphoma, Diffuse/EN/EP/*PA; Middle Age; Space-Time Clustering; Splenic Neoplasms/EN/EP/*PA; Stains and Staining; Tartrates/PD. .T Tartrate resistant acid phosphatase positive splenic lymphoma: a relatively benign condition occurring in a time-space cluster? .P JOURNAL ARTICLE. .W Conventional light and electron microscopic studies, together with cytochemical and immunocytochemical staining procedures, were carried out to ascertain whether the lymphomata of four elderly female patients living within 10 kilometers of each other, who presented within a short space of time with massive splenomegaly and varying cytopenia, belonged to any particular subgroup of lymphoma. In each case the lymphoma had a diffuse pattern and mature B cell phenotype. The malignant cells were of uniform cell type, slightly larger than admixed polymorphonuclear leucocytes, and showed minimal nuclear irregularity and positivity for tartrate resistant acid phosphatase (TRAP) staining. Their clinical and morphological features were compared with those of other lymphoproliferative disorders, but while sharing some features in common with each condition, this small group of patients seemed to have a unique combination of findings. The cytopenias of all four responded well after removal of the spleen and their disease has not been aggressive. It is concluded that these patients have a distinct subgroup of lymphoma, which it is important to recognise so that inappropriate use of aggressive cytotoxic drugs can be avoided. .A Kettle P; Morris TC; Markey GM; Alexander HD; Curry RC; Hayes D; Cameron CH; Toner PG. .I 275375 .U 91009911 .S J Clin Pathol 9101; 43(9):719-22 .M Antibodies, Monoclonal/*DU; Cytoplasmic Granules/UL; Human; Mast Cells/*UL; Mastocytosis/PA; Neoplasms/*UL. .T Use of monoclonal antibody KP1 for identifying normal and neoplastic human mast cells. .P JOURNAL ARTICLE. .W The monoclonal antibody KP1 (CD68) was used to stain normal and neoplastic monocytes and macrophages in routinely processed, paraffin wax embedded tissue: mast cells also exhibited strong, consistent cytoplasmic immunoreactivity. Light microscopic findings were corroborated by electron microscopical and immunocytochemical findings. The predominant sites of immunoreactivity were the specific intracytoplasmic granules of the mast cells. All mast cell subtypes--that is, normal and reactive mast cells, such as those in lymph nodes exhibiting chronic non-specific lymphadenitis, and malignant or neoplastic mast cells in various types of mastocytosis--reacted with this antibody. This finding is of diagnostic importance, because mast cell proliferation could be mistaken for histiocyte proliferation. It also supports the hypothesis that mast cells derive from the bone marrow. .A Horny HP; Schaumburg-Lever G; Bolz S; Geerts ML; Kaiserling E. .I 275376 .U 91009912 .S J Clin Pathol 9101; 43(9):723-7 .M Bone Marrow/*UL; Human; Nucleolus Organizer Region/*UL; Silver Nitrate/*; Stains and Staining. .T Argyrophilic nucleolar organiser region (AgNOR) staining in normal bone marrow cells. .P JOURNAL ARTICLE. .W Fifteen normal bone marrow aspirates were stained with the agyrophilic nucleolar organiser region (AgNOR) method. The results of the specific staining AgNORs as well as nuclear and cytoplasmic staining were analysed. A system was devised to characterise precisely the AgNORs present in the nuclei of bone marrow cells. Particular types of bone marrow cells had a characteristic AgNOR and non-AgNOR staining pattern. The bone marrow cells were identified easily and reliably with AgNOR staining and the method was especially useful for lymphocytes, plasma cells, erythroid cells, basophils/mast cells, monocytes and cells containing haemosiderin. The immature haemopoietic cells exhibited more and larger AgNORs than the more mature cells. It is concluded that AgNOR staining can be used to study bone marrow cells by providing additional information when used in conjunction with conventional stains. .A Nikicicz EP; Norback DH. .I 275377 .U 91009914 .S J Clin Pathol 9101; 43(9):732-7 .M Aged; Aged, 80 and over; Case Report; Granulosa Cell Tumor/ME/*PA; Human; Male; Receptors, Estrogen/*AN; Receptors, Progesterone/*AN; Testicular Neoplasms/ME/*PA; Tumor Markers, Biological/*AN. .T Testicular sex cord stromal tumour with granulosa cell differentiation: detection of steroid hormone receptors as a possible basis for tumour development and therapeutic management. .P JOURNAL ARTICLE. .W A testicular sex cord stromal tumour with granulosa cell differentiation, typical of granulosa cell tumours of the adult type, was investigated immunohistologically on snap frozen and paraffin wax embedded material. The predominance of vimentin and the additional expression of cytokeratin subtypes 8 and 18, as well as the negative staining for epithelial membrane antigen, accorded with results previously reported, for ovarian granulosa cell tumours; the lack of expression of desmoplakin, however, was a distinctive feature. Together with negative staining for leucocyte common antigen, the antigen pattern facilitates the differential diagnosis between granulosa cell tumour and undifferentiated carcinoma or gonadal lymphoma, although its suitability for differentiating within the group of gonadal stromal tumours seems to be limited. The small growth fraction, shown by the monoclonal antibody Ki-67, is typical of the clinical behaviour of granulosa cell tumours. The expression of oestrogen and progesterone receptors, also recently found in testicular Leydig cell tumours, may provoke new approaches to the management of testicular granulosa cell tumours, as well as a new hypothesis on the development of these tumours. .A Due W; Dieckmann KP; Niedobitek G; Bornhoft G; Loy V; Stein H. .I 275378 .U 91009915 .S J Clin Pathol 9101; 43(9):738-43 .M Adolescence; Adult; Aged; Duodenal Neoplasms/*PA; Duodenum/*PA; Female; Human; Male; Middle Age; Polyposis Syndrome, Familial/*PA; Prospective Studies; Stomach/*PA; Stomach Neoplasms/*PA. .T Upper gastrointestinal pathology in familial adenomatous polyposis: results from a prospective study of 102 patients. .P JOURNAL ARTICLE. .W Multiple gastric and duodenal biopsy specimens from 102 asymptomatic patients with familial adenomatous polyposis, taken during a prospective endoscopic screening programme were examined. One hundred patients had microscopic gastroduodenal pathology, often in the absence of macroscopic lesions. Adenomas were found in 94 patients in the duodenum, in the second and third parts. Hyperplasia of villous and crypt epithelium was also seen, sometimes in the absence of adenomas: this may be a precursor of neoplastic change. In the stomach fundic gland polyps were the commonest abnormality, seen microscopically in 44 patients. Chronic antral gastritis was common in patients without fundic polyps. Gastric adenomas were present in six patients, all of whom also had duodenal adenomas. If duodenal adenomas in familial adenomatous polyposis have a similar malignant potential to those in the colorectum sequential endoscopy and biopsy are necessary to detect cancer in these patients. .A Domizio P; Talbot IC; Spigelman AD; Williams CB; Phillips RK. .I 275379 .U 91009916 .S J Clin Pathol 9101; 43(9):744-7 .M Adult; Aged; Biopsy; Bromodeoxyuridine/*; Cell Division; Colonic Polyps/*PA; Female; Human; Immunoenzyme Techniques/*; Intestinal Mucosa/*PA; Male; Middle Age; Risk; Sigmoid/*PA; Support, Non-U.S. Gov't. .T Immunohistochemical detection of abnormal cell proliferation in colonic mucosa of subjects with polyps. .P JOURNAL ARTICLE. .W Previous studies have shown the presence of increased proliferation in the large bowel epithelium of those at high risk of developing colon cancer. An in vitro technique for labelling large bowel mucosa with the thymidine analogue bromodeoxyuridine (Brdu) was therefore developed and its ability to distinguish differences in mucosal proliferation between subjects with colorectal adenomas and normal controls was assessed. Sigmoid biopsy specimens from 15 subjects with polyps and 15 age and sex matched controls were labelled and the incorporated Brdu visualised with an immunohistochemical technique. Mean labelling index (LI) was significantly higher in those with polyps than in controls. Differences in the pattern of labelling in colonic crypts were compared by the generation of cumulative labelling distributions. Analysis showed a significant expansion of the proliferative compartment in the colon crypts of those with polyps. It is concluded that in vitro labelling with Brdu provides a useful method for the assessment of mucosal proliferation in subjects at high risk of developing colon cancer. .A Wilson RG; Smith AN; Bird CC. .I 275380 .U 91009918 .S J Clin Pathol 9101; 43(9):752-7 .M Antibodies, Monoclonal/*DU; Antigens/*AN; Antigens, Neoplasm/AN; Endothelium, Vascular/*IM; Human; Immunoenzyme Techniques; Support, Non-U.S. Gov't. .T JC70: a new monoclonal antibody that detects vascular endothelium associated antigen on routinely processed tissue sections. .P JOURNAL ARTICLE. .W A new monoclonal antibody, JC70, raised against a membrane preparation from a spleen affected by hairy cell leukaemia, recognises a membrane bound glycoprotein identical with that of the CD31 group of monoclonal antibodies. The antibody stains a fixation resistant epitope on endothelial cells in benign and malignant conditions in a wide variety of paraffin wax embedded tissue. JC70 stained malignant endothelial cells in 10 angiosarcomas with more consistency than monoclonal or polyclonal antibodies to factor VIII related antigen (FVIII-Rag). In four cases of Kaposi's sarcoma the antibody stained malignant endothelial cells but not spindle cells. It is concluded that antibody JC70 is of value for studying benign and malignant human vascular disorders in routinely processed tissue. .A Parums DV; Cordell JL; Micklem K; Heryet AR; Gatter KC; Mason DY. .I 275381 .U 91009919 .S J Clin Pathol 9101; 43(9):758-61 .M Acute Disease; Adnexitis/*IM/MI; Antibodies, Bacterial/*BI; Antibody Specificity; Antigens, Bacterial/IM; Chlamydia trachomatis/*IM; Chlamydia Infections/*DI; Female; Human; Immunoblotting; Immunoenzyme Techniques; Support, Non-U.S. Gov't. .T Antigen specific serum antibody response to Chlamydia trachomatis in patients with acute pelvic inflammatory disease. .P JOURNAL ARTICLE. .W Sera from 35 patients with acute pelvic inflammatory disease (PID) with and without Chlamydia trachomatis confirmed by culture and sera from 19 control patients with neither evidence of pelvic infection nor C trachomatis infection were studied for the presence of serum IgG, IgA, and IgM antibodies to C trachomatis using enzyme immunoassay (EIA) and immunoblotting techniques. There was no correlation between the antibody concentrations in the EIA and the spread of chlamydial infection, as determined by cervical, endometrial, and laparoscopic sampling for chlamydia. The immunoblot analysis showed antibodies to the major outer membrane protein (MOMP) of C trachomatis elementary bodies in all patients who had had C trachomatis isolated. Reactivity was also frequently observed against the 68, 62, 60, 45, and 31 kilodalton antigens. About 20 antigenic polypeptides were identified. Differences in antibody prevalence to specific chlamydial antigens, however, were not related to the site of chlamydial isolation or serum antibody concentrations observed with the EIA. The results indicate that patients with PID with and without upper genital tract infection with C trachomatis cannot be differentiated by reactivity of sera to specific chlamydial polypeptide antigens. The determination of a specific serum IgA antibody response by EIA was the most effective single test to discriminate between patients with and without acute chlamydial infection. .A Miettinen A; Heinonen PK; Teisala K; Punnonen R; Paavonen J. .I 275382 .U 91009920 .S J Clin Pathol 9101; 43(9):762-5 .M Adolescence; Biological Markers/BL; Child; Child, Preschool; Female; Gastrins/*BL; Gastritis/BL/MI; Helicobacter pylori/*; Helicobacter Infections/*BL; Human; Infant; Male; Pepsinogen/*BL; Prospective Studies; Severity of Illness Index. .T Serum pepsinogen I and gastrin concentrations in children positive for Helicobacter pylori. .P JOURNAL ARTICLE. .W Serum pepsinogen I, serum gastrin concentration, and inflammatory scores were measured in a population of 71 children undergoing upper gastrointestinal endoscopy for investigation of upper abdominal pain. Forty four were initially colonised with Helicobacter pylori. The indices were measured before treatment (in 71 children), one month (in 41 children), and six months (in 21 children) after stopping treatment. Before treatment there was a significant correlation between serum pepsinogen concentration, total inflammatory score, and H pylori state, but no correlation between serum gastrin concentrations and H pylori state. Similarly, the total inflammatory score and serum pepsinogen concentrations were significantly correlated. There was no such correlation in children negative for H pylori. After treatment the inflammatory score improved in those patients in whom H pylori had been eradicated. There was also a significant fall in serum pepsinogen I and serum gastrin concentration in those patients in whom H pylori had been eradicated. These results were similar to those found six months after treatment had been stopped. These findings suggest that the serum pepsinogen I concentration could be considered a useful marker for gastritis and can be used as an index of severity of gastritis in H pylori positive subjects. The measurement of serum gastrin concentrations does not give useful information. .A Oderda G; Vaira D; Dell'Olio D; Holton J; Forni M; Altare F; Ansaldi N. .I 275383 .U 91009921 .S J Clin Pathol 9101; 43(9):766-70 .M Antibodies, Viral/*BL; Enzyme-Linked Immunosorbent Assay/*; Human; IgG/*AN; Latex Fixation Tests/*MT; Rubella Virus/*IM. .T Latex enzyme immunoassay for measuring IgG antibodies to rubella virus. .P JOURNAL ARTICLE. .W A latex enzyme immunoassay (LEIA) for detecting IgG class antibody to rubella virus was compared with the latex agglutination test (LA) and a haemagglutination inhibition assay (HI). Of 243 sera tested, four discrepant results were observed among all three techniques, corresponding to borderline values. Except for one sample containing specific IgM class antibody, the difference between quantitative results from each pair of tests was always within a value corresponding to two doubling dilutions and was considered to have acceptable variation. The LEIA technique allowed 10 seroconversions to be detected, as determined by the other techniques. The LEIA required a single 1 in 8 sample dilution, took 30 minutes, and provided a useful alternative assay for the quantitation of rubella antibodies. .A Duverlie G; Roussel C; Driencourt M; Orfila J. .I 275384 .U 91009922 .S J Clin Pathol 9101; 43(9):771-3 .M Bacteriological Techniques/*; Enterobacteriaceae/*EN; Paper; Urea/*; Urease/AN/*ME. .T Use of urea filter paper disc to detect urease activity in Enterobacteriaceae by multipoint replication techniques. .P JOURNAL ARTICLE. .W A new method of detecting urease activity in Enterobacteriaceae was developed. An 8.5 cm filter paper disc impregnated with 20% urea and 0.5% bromocresol purple was placed on the surface of a glucose fermentation plate after inoculation with a multipoint replicator and overnight incubation. This method was compared with the commercially prepared Mast urea agar (Multipoint) and Fuscoe's Urea Plate Medium. A total of 240 routine isolates of Enterobacteriaceae were tested for urease activity using the three methods. Sixty five isolates were positive by the three methods while 33 isolates gave differing results. The urea disc method was more sensitive for detecting urease activity in isolates of Klebsiella species, Morganella morganii, and Yersinia enterocolitica. It also overcame the problem associated with the other two media of diffusion of alkali end products through the medium. .A Winter DB; McDermott SN. .I 275385 .U 91009923 .S J Clin Pathol 9101; 43(9):774-6 .M Antibiotics, Combined/PD; Endocarditis, Bacterial/*MI; Gentamicins/*PD; Human; Microbial Sensitivity Tests/MT; Netilmicin/PD; Penicillin G/*PD; Streptococcus/*DE. .T Multiple breakpoint method for measuring effect of antibiotics on endocarditis strains of streptococci. .P JOURNAL ARTICLE. .W The activity of penicillin alone and combined with aminoglycoside on endocarditis strains of streptococci was examined. Good assay reproducibility was obtained by the use of logarithmic phase cultures standardised by opacity, careful inoculation of well-plates, removal of antibiotic by membrane transfer and incubating survival counts in hydrogen plus carbon dioxide. The use of 10-fold intervals for penicillin concentration simplified assay design without loss of efficiency. .A Marks J; Paull A. .I 275386 .U 91009924 .S J Clin Pathol 9101; 43(9):777-9 .M Adult; Blood Specimen Collection/*; Hematologic Diseases/*BL/CO; Human; Leukemia/BL/CO; Lymphoma/BL/CO; Neutropenia/BL; Septicemia/*BL/CO. .T Effect of sample volume on yield of positive blood cultures from adult patients with haematological malignancy. .P JOURNAL ARTICLE. .W Six hundred and sixteen blood samples from patients with haematological malignancy were each distributed equally among three identical cells in a Malthus Microbiological Growth Analyser. The mean (SD) volumes inoculated into sets in which one, two, or three of the three bottles were positive were 37.7 (10.1) ml, 37.4 (12.9) ml, and 37.7 (10.5) ml, respectively. Overall, clinically important organisms were isolated from one bottle only with 18 cultures, from two bottles only with 19 cultures, and from all three bottles in a set with 104 cultures. If the yield from a single bottle inoculated with a mean volume of 12.6 ml blood is taken as 100%, the yield from 25.2 ml in two bottles was 110.7% and the yield from 37.7 ml in three bottles was 115.6%. The increased yield from increased volume was considerably lower than that reported from unselected groups of patients, which suggests that the magnitude of bacteriaemia is greater in patients with neutropenia. The isolation of infecting organisms from the blood of patients with neutropenia is, however, particularly important in directing chemotherapy and consequently 45 ml blood samples from these patients continue to be requested. .A Brown DF; Warren RE. .I 275387 .U 91009925 .S J Clin Pathol 9101; 43(9):780 .M Aged; Case Report; Female; Human; Lipoma/*PA; Liver Neoplasms/*PA. .T True lipoma of Glisson's capsule [letter] .P LETTER. .A Sossai P; Barbazza R. .I 275388 .U 91009926 .S J Clin Pathol 9101; 43(9):780-1 .M Acquired Immunodeficiency Syndrome/*CO; Adult; Case Report; Human; Lymphocytes/*PA; Male; Salivary Gland Diseases/*PA. .T Benign lymphoepithelial lesion of salivary gland in a patient with AIDS [letter] .P LETTER. .A Knox WF; McWilliam LJ; Banerjee SS. .I 275389 .U 91009927 .S J Clin Pathol 9101; 43(9):781 .M Acinetobacter Infections/*; Adult; Case Report; Equipment Contamination; Female; Hip Prosthesis/*; Human; L Forms/*. .T Acinetobacter spp L-form infection of a cemented Charnley total hip replacement [letter] .P LETTER. .A Haley S; Paul J; Crook DW; White SH. .I 275390 .U 91009928 .S J Clin Pathol 9101; 43(9):782 .M Fibrinogen/*AN; Human; Reference Standards. .T Fibrinogen standards [letter] .P LETTER. .A Hogg P; Prangnell D. .I 275391 .U 91009929 .S J Clin Pathol 9101; 43(9):782 .M Adult; Case Report; Female; Human; Lymphadenitis/*PA; Necrosis; Neutrophils/*; Western Samoa. .T Necrotising lymphadenitis without granulocytic infiltration: case from Western Samoa [letter] .P LETTER. .A Paksoy N. .I 275392 .U 91009930 .S J Clin Pathol 9101; 43(9):782-3 .M Hepatitis B/*DI; Hepatitis B Antibodies/*AN; Hepatitis B Core Antigens/*IM; Human; IgM/*AN. .T Anti-HBc IgM assays and diagnosis of acute hepatitis B [letter] [see comments] .P LETTER. .A Morris DJ. .I 275393 .U 91009931 .S J Clin Pathol 9101; 43(9):783 .M Aspergillosis/*CO; Cholecalciferols/*TU; Human; Leukemia/*CO; Lung Diseases, Fungal/*CO. .T Pulmonary aspergillosis in patients with leukaemia [letter; comment] .P COMMENT; LETTER. .A Kelsey SM; Newland AC; Van der Walt J; Doran H. .I 275394 .U 91009932 .S J Clin Pathol 9101; 43(9):783-4 .M Adult; Case Report; Cyclosporins/*AE; Female; Human; Magnesium/*BL. .T Potential benefit of 1-alpha-cholecalciferol in hypomagnesaemia by cyclosporin [letter] .P LETTER. .A Pearce CJ; Davies JM. .I 275395 .U 91009933 .S J Clin Pathol 9101; 43(9):784 .M Female; Human; Ovarian Neoplasms/*ME; Parathyroid Hormones/*; Proteins/*AN. .T Parathyroid hormone related peptide in ovarian carcinoma [letter] .P LETTER. .A Burton PB; Knight DE; Quirke P; Smith R; Moniz C. .I 275396 .U 91009934 .S J Clin Pathol 9101; 43(9):784-5 .M Adolescence; Adult; Aged; Aged, 80 and over; Enzyme Precursors/*AN; Female; Human; Ovarian Cysts/*ME; Renin/*AN. .T Prorenin in ovarian cyst fluid [letter] .P LETTER. .A Bessant CM; Charlton PA; Price-Jones MJ; Kay J; Reid WA. .I 275397 .U 91009983 .S J Am Acad Dermatol 9101; 23(2 Pt 1):167-86 .M Animal; Bites and Stings/MI; Borrelia burgdorferi/IM/IP; Child; Disease Reservoirs; Disease Vectors; Enzyme-Linked Immunosorbent Assay; Female; Human; Lyme Disease/*/CO/DT/IM/MI; Male; Pregnancy; Seasons; Sex Factors; Support, Non-U.S. Gov't; Tetracyclines/TU; Ticks/MI; Time Factors; United States. .T The many faces and phases of borreliosis. I. Lyme disease [published erratum appears in J Am Acad Dermatol 1991 Apr;24(4):663] [see comments] .P JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC. .W Lyme disease is increasingly being reported throughout the United States and many parts of the world. Borrelia burgdorferi, the etiologic agent of Lyme disease, is a spirochete that, not unlike the treponema of syphilis, can cause a spectrum of disease from the initial skin lesion, through widely varied symptoms and signs, to chronic neurologic and arthritic disability. The borrelial spirochete and Lyme disease are the subject of this review. A subsequent article will review other definite and possible cutaneous manifestations of borreliosis. .A Abele DC; Anders KH. .I 275398 .U 91009984 .S J Am Acad Dermatol 9101; 23(2 Pt 1):189-98 .M Cells, Cultured; DNA/AN; DNA Probes; Female; Graft Survival/*; Human; Keratin/AN; Keratosis/PA; Skin/ME/PA/UL; Skin Transplantation/*MT; Skin Ulcer/GE/ME/*SU; Wound Healing/PH. .T Cultured epidermal autografts and allografts: a study of differentiation and allograft survival. .P JOURNAL ARTICLE. .W Cultured epidermal sheets were examined before and at various times after grafting on skin ulcer beds. Before grafting, the sheet consisted of four to five layers of keratinocytes with incomplete differentiation. Ten days after grafting, graft recipient sites showed compact hyperkeratosis, a normal-appearing epidermis, and a flat dermoepidermal junction. At 6 months, the stratum corneum had a basket-weave appearance but the dermoepidermal junction remained flat. Monoclonal antibodies to keratins 14 and 10 showed normal basal and suprabasal localization, respectively. Electron microscopy showed a normal basement membrane with anchoring fibrils. LH7:2, a monoclonal antibody that binds to the type VII collagen molecule, stained the dermoepidermal junction in all biopsy specimens. AE-1, an antibody that stains suprabasal cells in hyperproliferative skin, was expressed suprabasally for up to 12 weeks after healing (16 weeks after grafting), but expression was confined to the basal layer at 18 weeks after healing (6 months after grafting). Anti-involucrin staining was found in the deeper layers of the epidermis up to 12 weeks after healing (16 weeks after grafting) but had receded to a normal distribution in upper spinous and granular layers at 18 weeks (6 months after grafting). Overall, the histologic patterns observed in recipient sites during the first 4 months after grafting resembled those observed for 10 to 14 days in newly healed epidermis and in hyperproliferative states such as psoriasis. In four sex-mismatched graft sites, specimens were reacted with a biotinylated probe to the Y chromosome by in situ hybridization. Lack of Y chromosome-positive cells suggested that host keratinocytes had replaced the allografts. Multilocus DNA analysis in one patient confirmed this observation. Our data suggest that an altered state of epithelial maturation persists for several months after culture grafting, with restoration of the normal pattern by 6 months. No differences were detected between autografted and allografted sites. .A Phillips TJ; Bhawan J; Leigh IM; Baum HJ; Gilchrest BA. .I 275399 .U 91009985 .S J Am Acad Dermatol 9101; 23(2 Pt 1):198-201 .M Autoantibodies/*AN; Cardiolipins/*IM; Enzyme-Linked Immunosorbent Assay; Female; Human; Male; Rheumatoid Factor/IM; Scleroderma, Systemic/CL/*IM; Thrombocytopenia/IM. .T Clinical manifestations in anticardiolipin antibody-positive patients with progressive systemic sclerosis. .P JOURNAL ARTICLE. .W Anticardiolipin antibody-positive patients with progressive systemic sclerosis were analyzed. Elevated anticardiolipin antibody titers were observed in 13 of 40 cases (33%). Anticardiolipin antibody titer was significantly higher in patients with progressive systemic sclerosis type 1 than in those with type 2 or type 3. Occurrence of anticardiolipin antibody was significantly more frequent in patients positive for anti-nRNP antibodies, rheumatoid factor, or thrombocytopenia. In contrast, patients with proximal scleroderma, scarring, or esophageal hypomotility were positive for anticardiolipin antibody less frequently. These results suggest that anticardiolipin antibody might be closely associated with lupuslike clinical manifestations in a subset of progressive systemic sclerosis or definite progressive systemic sclerosis with thrombocytopenia, rheumatoid factor, or anti-nRNP antibodies. .A Katayama I; Otoyama K; Kondo S; Nishioka K; Nishiyama S. .I 275400 .U 91009986 .S J Am Acad Dermatol 9101; 23(2 Pt 1):202-4 .M Adrenal Cortex Hormones/TU; Adult; Case Report; Eosinophilia/DI/DT/*PA; Erythroderma/DT/*PA; Human; HIV Infections/DI/*PA; Male; Middle Age; Prednisone/AD/TU; Pruritus/DT; PUVA Therapy; Skin/PA; Syndrome. .T Hypereosinophilic syndrome with unusual cutaneous manifestations in two men with HIV infection. .P JOURNAL ARTICLE. .W We report two men with human immunodeficiency virus infection who had unusual cutaneous manifestations of hypereosinophilic syndrome, exfoliative erythroderma, and linear flagellate plaques. In the first patient the cutaneous disease was the initial manifestation, and in the second the skin was the only organ affected. We also describe a favorable response to systemic corticosteroids and to psoralen with UVA phototherapy in one patient. .A May LP; Kelly J; Sanchez M. .I 275401 .U 91009987 .S J Am Acad Dermatol 9101; 23(2 Pt 1):205-13 .M Adult; Blotting, Southern/MT; Child; Child Abuse, Sexual/DI; Child, Preschool; Condylomata Acuminata/*MI/PA/SU; Female; Human; Infant; Male; Papillomaviruses/GE/*IP; Skin/PA; Support, Non-U.S. Gov't; Warts/*MI/PA. .T Condylomata acuminata in children: frequent association with human papillomaviruses responsible for cutaneous warts. .P JOURNAL ARTICLE. .W To identify the papillomavirus types associated with condylomata acuminata in children and to evaluate their mode of transmission, we studied 32 children with anogenital warts. External condylomata were found in 12 of their mothers and in 10 of their fathers. Ten mothers, including two without external lesions, had cervical condylomata. Blot hybridization studies disclosed a genital human papillomavirus (HPV) in 14 of 27 children (HPV-6 in 12 and HPV-11 in two) and in 8 of 14 patients (HPV-6 in all). HPV-6 was found in another child by the polymerase chain reaction technique. Infection occurred most likely at birth or from nonsexual contact, but sexual abuse could not be excluded in one 11-year-old girl. Cutaneous HPV-2 was found in seven children and as yet uncharacterized papillomaviruses were found in two children. Three mothers of HPV-2-infected children had common hand warts, and two children had subungual warts. This study shows the frequent nonsexual transmission of genital papillomaviruses in children and the unexpectedly high association of children's condylomata with papillomaviruses responsible for skin warts, possibly transmitted by heteroinoculation or autoinoculation. .A Obalek S; Jablonska S; Favre M; Walczak L; Orth G. .I 275402 .U 91009988 .S J Am Acad Dermatol 9101; 23(2 Pt 1):214-20 .M Antibodies, Monoclonal/DU; Biopsy; Human; Immunohistochemistry; Lymphocytes, Tumor-Infiltrating/*/IM; Phenotype; Skin Neoplasms/*IM/PA; T-Lymphocyte Subsets/IM. .T Activation and inducer subset phenotype of the lymphocytic infiltrate around epidermally derived tumors. .P JOURNAL ARTICLE. .W An in situ analysis of the mononuclear cell infiltrate found in association with a range of benign, premalignant, and malignant epidermal tumors is described. The predominant cell phenotype was that of the recently described immunoregulatory helper/inducer T lymphocyte. A large number of lymphocytes expressed antigens associated with cellular activation, suggesting an ongoing immunologic response by the host against the tumor, although evidence of in situ proliferation of these cells was lacking. These findings suggest that the infiltrate found in association with cutaneous tumors does not represent passive accumulation of lymphocytes from the circulation but rather an active antitumor response. .A Markey AC; Churchill LJ; Allen MH; MacDonald DM. .I 275403 .U 91009989 .S J Am Acad Dermatol 9101; 23(2 Pt 1):220-8 .M Adolescence; Adult; Chronic Disease; Female; Graft vs Host Disease/DI/*DT; Human; Immunosuppressive Agents/AD/TU; Keratinocytes/RE; Lichen Planus/*DT/ET/PA; Liver Diseases/DT/ET; Male; Mouth Mucosa/PA; PUVA Therapy/*/AE/MT; T-Lymphocytes/RE. .T Photochemotherapy improves chronic cutaneous graft-versus-host disease. .P JOURNAL ARTICLE. .W We have used oral psoralen photochemotherapy (PUVA) to treat four patients with chronic graft-versus-host disease of the skin, oral mucosa, and liver, who had responded only partially to long-term immunosuppressive therapy (prednisolone, cyclosporine, azathioprine). PUVA therapy was delivered to the entire skin but not to the oral mucosa, and immunosuppressive therapy was continued in all patients. Two patients' skin lesions improved considerably; the oral lesions healed and did not recur in one. Immunosuppressive therapy could be reduced in these two patients. One patient with sicca signs did not improve. One patient had to interrupt PUVA therapy because of side effects attributed to 8-methoxypsoralen (nausea and vomiting). No flare of acute cutaneous graft-versus-host disease was noted during PUVA therapy. Chronic graft-versus-host disease of the liver did not improve in any patient. .A Volc-Platzer B; Honigsmann H; Hinterberger W; Wolff K. .I 275404 .U 91009990 .S J Am Acad Dermatol 9101; 23(2 Pt 1):229-35 .M Adolescence; Adult; Aged; Case Report; Child; Collagen; Diagnosis, Differential; Endothelium, Vascular/PA; Female; Human; Lymphangioma/*PA/SU; Male; Middle Age; Skin/PA; Skin Neoplasms/*PA/SU. .T Benign lymphangioendothelioma. .P JOURNAL ARTICLE. .W We have studied eight cases of an acquired lymphatic endothelial lesion for which we propose the name "benign lymphangioendothelioma." The lesions developed as solitary, slowly extending, erythematous macules and plaques, usually occurring on the extremities or the shoulders in adolescents or adults. The characteristic histopathologic feature is permeation of the dermal collagen by flattened, endothelium-lined channels and spaces. Hemorrhage, iron deposition, and inflammation were not part of the lesion. Ulex europaeus agglutinin I labeled the lesional endothelial cells consistently, but factor VIII-related antigen labeling was negative. This histologic pattern and the special studies suggested a lymphatic lesion. Surgical excision, performed in six patients, was not followed by recurrence. .A Jones EW; Winkelmann RK; Zachary CB; Reda AM. .I 275405 .U 91009991 .S J Am Acad Dermatol 9101; 23(2 Pt 1):236-41 .M Aged; Aged, 80 and over; Case Report; Clofazimine/AD/*AE/TU; Dermatitis Medicamentosa/*ET; Female; Human; Leprosy, Lepromatous/*DT; Male; Neuronal Ceroid-Lipofuscinosis/CI; Pigmentation Disorders/*CI; Skin/PA/UL. .T Skin pigmentation from clofazimine therapy in leprosy patients: a reappraisal. .P JOURNAL ARTICLE. .W Skin biopsy specimens from two lepromatous leprosy patients with dark brown pigmentation who were receiving long-term clofazimine therapy were studied. Ceroid-lipofuscin pigment was demonstrated inside macrophages that contained numerous phagolysosomes. These contained lipids and clofazimine that appeared as electron-lucent vacuoles and a lipofuscin pigment that was electron dense, granular, and lamellated. Although the presence of the drug in tissues contributed to the skin pigmentation, the main cause was a drug-induced, reversible ceroid lipofuscinosis. .A Job CK; Yoder L; Jacobson RR; Hastings RC. .I 275406 .U 91009992 .S J Am Acad Dermatol 9101; 23(2 Pt 1):242-6 .M Dysplastic Nevus Syndrome/*ME/PA; Estrogens/ME; Female; Human; Male; Melanoma/*ME/PA; Nevus/*ME/PA; Progesterone/ME; Receptors, Estrogen/*AN; Skin Neoplasms/*ME/PA. .T Absence of estrogen receptors in dysplastic nevi and malignant melanoma. .P JOURNAL ARTICLE. .W Benign nevi, dysplastic nevi, and primary and metastatic malignant melanomas were evaluated for the presence of sex hormone binding and estrogen receptor protein. We have confirmed the observation of Ellis et al. that some pigmented lesions possess sex hormone-binding proteins. We could not demonstrate a true estrogen receptor in any benign nevi, dysplastic nevi, primary melanomas, or metastatic melanomas. Thus the ability to bind estrogen or progesterone does not correlate with the presence of a true estrogen receptor. Lack of nuclear estrogen receptors suggests that the influence of estrogen on the pathophysiology of melanoma or of benign melanocytic nevi may not be significant. .A Lecavalier MA; From L; Gaid N. .I 275407 .U 91009993 .S J Am Acad Dermatol 9101; 23(2 Pt 1):247-9 .M Case Report; Female; Human; Male; Middle Age; Myelodysplastic Syndromes/*CO; Neutrophils/*PA; Prednisolone/TU; Skin/*PA; Skin Diseases/BL/DT/*PA. .T Neutrophilic dermatosis with myelodysplastic syndrome: nuclear segmentation anomalies of neutrophils in the skin lesion and in peripheral blood. .P JOURNAL ARTICLE. .W Neutrophilic dermatosis developed in two patients with myelodysplastic syndrome. Biopsy specimens of their skin lesions showed marked infiltration by neutrophils with nuclear anomalies, that is, hyposegmentation (pseudo-Pelger-Huet anomaly) or hypersegmentation. Peripheral blood and bone marrow neutrophils had similar anomalies. To our knowledge, this is the first report of nuclear segmentation anomalies of neutrophils in neutrophilic dermatosis skin lesions of patients with myelodysplastic syndrome. .A Morioka N; Otsuka F; Nogita T; Igisu K; Urabe A; Ishibashi Y. .I 275408 .U 91009994 .S J Am Acad Dermatol 9101; 23(2 Pt 1):250-4 .M Adult; Case Report; Eccrine Glands/PP; Emollients/AD/TU; Female; Fluocinonide/AD/TU; Human; Hyperhidrosis/DI/*ET; Injections, Intradermal; Leg Dermatoses/*CO/DT; Male; Methacholine Chloride/AD; Middle Age; Myxedema/*CO/DT; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Localized hyperhidrosis in pretibial myxedema. .P JOURNAL ARTICLE. .W Two cases of spontaneous hyperhidrosis limited to pretibial myxedema lesions were studied. Quantitative measurements of stimulated eccrine sweat were made after the intradermal injection of methacholine. The sweat rate was two to four times greater in the lesional skin than in perilesional skin. Eccrine secretory glands in excisional biopsy specimens from the pretibial lesions were significantly larger than those in perilesional skin. To our knowledge, hyperhidrosis localized to areas of pretibial myxedema has not been reported. .A Gitter DG; Sato K. .I 275409 .U 91009995 .S J Am Acad Dermatol 9101; 23(2 Pt 1):254-6 .M Adenocarcinoma/EP; Carcinoma, Merkel Cell/EP; Female; Fibrosarcoma/EP; Human; Incidence; Liposarcoma/EP; Lymphoma, T-Cell, Cutaneous/DI/*EP; Male; Minnesota/EP; Mycosis Fungoides/DI/EP; Paget's Disease, Extra-Mammary/EP; Sampling Studies; Skin Neoplasms/DI/*EP; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Sweat Gland Neoplasms/EP. .T Incidence of cutaneous T cell lymphoma and other rare skin cancers in a defined population. .P JOURNAL ARTICLE. .W Between 1970 and 1984 in Rochester, Minnesota, rare skin cancers developed in 15 local residents: cutaneous T cell lymphoma (six subjects), dermatofibrosarcoma protuberans (four), adenocarcinoma of sweat glands (two), Merkel cell carcinoma (one), liposarcoma (one), and extramammary Paget's disease (one). These cases were identified through a unique computerized retrieval system that is maintained at the Mayo Clinic for the population of Rochester, Minnesota. The annual incidences of these cancers in the Rochester population were 0.9, 0.5, 0.3, 0.2, 0.2, and 0.2 per 100,000 residents, respectively (standardized to 1980 U.S. population). To our knowledge, this is the first report of the incidences of these rare skin cancers in a well-defined population. .A Chuang TY; Su WP; Muller SA. .I 275410 .U 91009996 .S J Am Acad Dermatol 9101; 23(2 Pt 1):257-62 .M Adult; Aged; Aged, 80 and over; Case Report; Chilblains/ET/*PA/TH; Child; Diagnosis, Differential; Female; Human; Lymphocytes/PA; Male; Nifedipine/AD/AE/TU; San Francisco; Skin/PA. .T Chilblains (perniosis). .P JOURNAL ARTICLE. .W Unfamiliarity of physicians with chilblains (perniosis) gives rise to unnecessary hospital admissions with expensive laboratory and radiologic evaluations and, at times, hazardous therapy. Seven cases of chilblains were seen in San Francisco from November 1986 through January 1987. The patients presented with pruritic, at times painful, purple acral patches or plaques on the fingers, toes, and nose after exposure to a cool or a cold, damp environment. Histologic examination in two cases revealed a perivascular lymphocytic infiltrate with endothelial swelling of the subcutaneous fat and of the upper and lower dermal plexus. .A Goette DK. .I 275411 .U 91009997 .S J Am Acad Dermatol 9101; 23(2 Pt 1):263-8 .M Adult; Dose-Response Relationship, Drug; Double-Blind Method; Human; Hypersensitivity, Immediate/*IM/PA; Injections, Intradermal; Leukocyte Count; Male; Plant Extracts/*PD; Platelet Activating Factor/*AI; Skin/*IM/PA; Skin Window Technique. .T Platelet activating factor-induced clinical and histopathologic responses in atopic skin and their modification by the platelet activating factor antagonist BN52063. .P CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL. .W The clinical and histopathologic responses to intradermal platelet-activating factor (PAF-acether) in atopic subjects, without evidence of atopic dermatitis are documented. An immediate acute wheal and flare reaction was observed in all volunteers. Histopathologically, the reaction was characterized by a predominantly neutrophilic response, which was seen at 30 minutes and was maximal at 4 hours. Eosinophils were observed in the infiltrate as early as 30 minutes after injection, and were maximal by 12 hours. The specific PAF-acether antagonist BN52063 antagonized the acute flare response to intradermal PAF-acether but had little effect on cellular recruitment at the site of injection. .A Markey AC; Barker JN; Archer CB; Guinot P; Lee TH; MacDonald DM. .I 275412 .U 91009998 .S J Am Acad Dermatol 9101; 23(2 Pt 1):269-79 .M Anesthetics, Local/AE/BL; Anti-Infective Agents, Local/TU; Antibiotics/TU; Female; Human; Pregnancy; Pregnancy Complications, Neoplastic/*SU; Risk Factors; Skin Neoplasms/*SU. .T Cutaneous surgery and the pregnant patient. .P JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC. .W Cutaneous surgery in 34 pregnant women is described. The main indication for surgery was the diagnosis and/or treatment of malignancy. Surgery during the period of organogenesis (15 to 56 days) should be avoided when possible. Patients should be positioned on the left side during the procedure to avoid the supine hypotensive syndrome. Monitoring of the fetal heartbeat is desirable. Local anesthetics, penicillin, and erythromycin are safe if used carefully. Acetaminophen is the analgesic of choice. Exposure to the sun should be avoided during the perioperative period. .A Gormley DE. .I 275413 .U 91009999 .S J Am Acad Dermatol 9101; 23(2 Pt 1):280-7 .M Human; Skin Diseases/*DT. .T Dermatologic therapy: 1989. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .A Coskey RJ. .I 275414 .U 91010000 .S J Am Acad Dermatol 9101; 23(2 Pt 1):288-94 .M Comparative Study; Human; Skin/*PA; Skin Neoplasms/PA/*SU. .T Comparison of methods for checking surgical margins. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Surgical margins of a cutaneous neoplasm can be evaluated by various combinations of three major types of sections: vertical (perpendicular), horizontal (parallel), and oblique (Mohs method). Vertical sections may run transversely through tumor (breadloaf method), longitudinally through tumor (breadloaf-cross method), or peripheral to the tumor. The peripheral (perimeter) sectioning methods are the only methods that can evaluate almost 100% of the margin, but they have the disadvantage of not showing the relationship of the tumor to its margin, which can be seen clearly with the vertical transverse sections. Seven methods of checking surgical margins are compared and contrasted. None of these is judged to be perfect or best. .A Rapini RP. .I 275415 .U 91010001 .S J Am Acad Dermatol 9101; 23(2 Pt 1):295-9 .M Adult; Atrophy; Fibroma/ET/PA/SU; Human; Infant, Newborn; Middle Age; Scleredema Adultorum/CO/IM/MI; Skin/PA; Skin Diseases/*/DT/ET/PA/SU. .T Diseases of the dermis. .P JOURNAL ARTICLE. .A Lebwohl M; Phelps R; Gordon M; Fleischmajer R. .I 275416 .U 91010002 .S J Am Acad Dermatol 9101; 23(2 Pt 1):300-7 .M Chronic Disease; Dermatitis, Contact/*/DT/IM; Female; Hand Dermatoses/IM/TH; Human; Irritants/AE; Male; Occupational Dermatitis/EP/IM/TH; Prognosis; Protective Clothing; Rubber/AE; Workmen's Compensation. .T The prognosis of contact dermatitis. .P JOURNAL ARTICLE; REVIEW; REVIEW, MULTICASE. .W This article reviews the prognosis of contact dermatitis, particularly of occupational contact dermatitis. Most studies document a poor prognosis for occupational and nonoccupational contact dermatitis. The prognoses of occupational and nonoccupational contact dermatitis, irritant contact dermatitis, and allergic contact dermatitis are similar. Only a minority of studies on the prognosis of occupational contact dermatitis have found that a job change by the affected worker leads to clearing of the dermatitis. Dermatologic and nondermatologic factors associated with a poor prognosis are discussed. .A Hogan DJ; Dannaker CJ; Maibach HI. .I 275417 .U 91010003 .S J Am Acad Dermatol 9101; 23(2 Pt 1):308-10 .M Adult; Age Factors; Female; Human; Life Expectancy; Male; Melanoma/EP/*MO; Middle Age; Skin Neoplasms/EP/*MO; Support, U.S. Gov't, P.H.S.; United States/EP. .T Years of potential life lost: another indicator of the impact of cutaneous malignant melanoma on society. .P JOURNAL ARTICLE. .W Years of potential life lost (YPLL) is an indicator of premature mortality that complements traditional incidence and mortality rates and that facilitates comparisons among different cancers. We calculated YPLL from cutaneous melanoma and 11 other cancers routinely recorded and tracked by Surveillance, Epidemiology and End Results (SEER). YPLL from cutaneous melanoma ranked eighth for persons younger than 65 years of age and fourth for those 20 to 49 years of age. An average of 17.1 YPLL per death were due to melanoma, one of the highest rates for adult-onset cancers. The results of our study, the first to apply YPLL to cutaneous melanoma, emphasize the disproportionate impact of this cancer on young and middle-aged adults and reemphasize the importance of this cancer as a public health priority. .A Albert VA; Koh HK; Geller AC; Miller DR; Prout MN; Lew RA. .I 275418 .U 91010004 .S J Am Acad Dermatol 9101; 23(2 Pt 1):311-5 .M Dermatology/*HI; Europe; History of Medicine, 17th Cent.; History of Medicine, 18th Cent.; History of Medicine, 19th Cent.; History of Medicine, 20th Cent.; Human; Philosophy; Skin Diseases/HI. .T Dermatology and the history of ideas. .P HISTORICAL ARTICLE; JOURNAL ARTICLE. .A Wolf JE Jr. .I 275419 .U 91010005 .S J Am Acad Dermatol 9101; 23(2 Pt 1):316-7 .M Adult; Carcinoma, Basal Cell/*SU; Cryosurgery/*; Eyelid Neoplasms/*SU; Female; Follow-Up Studies; Human; Male; Middle Age; Neoplasm Recurrence, Local; Postoperative Complications. .T Cryosurgical management of basal cell carcinoma of the eyelid: a 10-year experience. .P JOURNAL ARTICLE. .A Biro L; Price E. .I 275420 .U 91010007 .S J Am Acad Dermatol 9101; 23(2 Pt 1):318-9 .M Aged; Carcinoma, Basal Cell/*PA; Case Report; Chronic Disease; Fingers/*; Human; Male; Skin Neoplasms/*PA; Skin Ulcer/*PA; Ultraviolet Rays/AE. .T Basal cell carcinoma presenting as a chronic finger ulcer. .P JOURNAL ARTICLE. .A West JR; Berman B. .I 275421 .U 91010008 .S J Am Acad Dermatol 9101; 23(2 Pt 1):320-1 .M Cyclosporins/AD/*AE/BL/ME; Drug Therapy, Combination; Human; Methotrexate/AD/*AE/BL/PD; Psoriasis/*DT. .T Cyclosporine and methotrexate: a dangerous combination. .P JOURNAL ARTICLE. .A Korstanje MJ; van Breda Vriesman CJ; van de Staak WJ. .I 275422 .U 91010009 .S J Am Acad Dermatol 9101; 23(2 Pt 1):321-2 .M Acne/DT; Adult; Case Report; Dermatitis Medicamentosa/*ET; Facial Dermatoses/*CI; Female; Human; Isotretinoin/*AE; Patch Tests; Photosensitivity Disorders/*CI. .T Photoaggravated allergic reaction to isotretinoin. .P JOURNAL ARTICLE. .A Auffret N; Bruley C; Brunetiere RA; Decot MC; Binet O. .I 275423 .U 91010010 .S J Am Acad Dermatol 9101; 23(2 Pt 1):322-4 .M Adult; Case Report; Female; Granuloma/*ET/PA/TH; Human; Male; Middle Age; Recurrence; Silica/*AE; Skin Diseases/*ET/PA/TH; Time Factors. .T Spontaneous resolution of silica granuloma. .P JOURNAL ARTICLE. .A Bovenmyer DA; Landas SK; Bovenmyer JA. .I 275424 .U 91010011 .S J Am Acad Dermatol 9101; 23(2 Pt 1):324-6 .M Case Report; Human; Male; Middle Age; Skin/*PA/PS; Skin Diseases, Parasitic/*PA/PS; Strongyloidiasis/DT/*PA; Thiabendazole/AD/TU. .T The thumbprint sign: rapid diagnosis of disseminated strongyloidiasis. .P JOURNAL ARTICLE. .A Bank DE; Grossman ME; Kohn SR; Rabinowitz AD. .I 275425 .U 91010012 .S J Am Acad Dermatol 9101; 23(2 Pt 1):327-8 .M Child; Epidermolysis Bullosa/*PA; Human; Male; Pigmentation Disorders/PA; Poikiloderma Congenitale/*PA; Skin/UL. .T Kindler syndrome and epidermolysis bullosa simplex [letter; comment] .P COMMENT; LETTER. .A Prendiville JS; Fine JD; Esterly NB. .I 275426 .U 91010013 .S J Am Acad Dermatol 9101; 23(2 Pt 1):328-9 .M Human; Occlusive Dressings/*; Time Factors; Water Loss, Insensible/*; Wound Healing. .T Measurement of transepidermal water loss [letter; comment] .P COMMENT; LETTER. .A Bolton L; Pirone L. .I 275427 .U 91010014 .S J Am Acad Dermatol 9101; 23(2 Pt 1):329 .M Aged; Female; Great Britain/EP; Human; Male; Multiple Sclerosis/*CO/EP; Pemphigoid, Bullous/*CO/EP. .T Bullous pemphigoid and multiple sclerosis [letter; comment] .P COMMENT; LETTER. .A Gebauer K; Cox J; Gartside J; Navaratnam T. .I 275428 .U 91010015 .S J Am Acad Dermatol 9101; 23(2 Pt 1):329-30 .M Behcet's Syndrome/*IM; Complement 3/AN; Fluorescent Antibody Technique/*; Human; Immunoglobulins/AN; Skin/*IM. .T Skin hyperreactivity response (pathergy) in Behcet's disease: usefulness of direct immunofluorescence [letter; comment] .P COMMENT; LETTER. .A Wechsler J; Wechsler B; Revuz J; Godeau P. .I 275429 .U 91010016 .S J Am Acad Dermatol 9101; 23(3 Pt 1):401-10 .M Acrodermatitis/MI; Borrelia burgdorferi/*; Chronic Disease; Human; Lyme Disease/*CO/MI/PP; Lymphoid Tissue/MI. .T The many faces and phases of borreliosis II. .P JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC. .W Borrelia burgdorferi, the etiologic agent of Lyme disease, has also been associated with other cutaneous conditions. Acrodermatitis chronica atrophicans and lymphadenosis benigna cutis are also caused by B. burgdorferi. Recent evidence links some cases of progressive facial hemiatrophy of Parry-Romberg, benign lymphocytic infiltrate of the skin (Jessner-Kanof), lichen sclerosus et atrophicus, morphea, and Shulman syndrome with borreliae. This article reviews the manifestations of the diseases definitely linked to borreliosis and the evidence linking borreliae to progressive facial hemiatrophy, benign lymphocytic infiltrate, lichen sclerosus et atrophicus, morphea, and Shulman syndrome. .A Abele DC; Anders KH. .I 275430 .U 91010017 .S J Am Acad Dermatol 9101; 23(3 Pt 1):413-21 .M Adolescence; Adult; Aged; British Columbia/EP; Carcinoma, Basal Cell/*EP; Carcinoma, Squamous Cell/*EP; Child; Child, Preschool; Female; Head and Neck Neoplasms/EP; Human; Infant; Male; Melanoma/*EP; Middle Age; Registries; Skin Neoplasms/*EP. .T Trends in basal cell carcinoma, squamous cell carcinoma, and melanoma of the skin from 1973 through 1987. .P JOURNAL ARTICLE. .W Major increases have occurred in the incidence of basal cell carcinoma and squamous cell carcinoma of the skin, as well as in cutaneous malignant melanoma during the period 1973 through 1987 in British Columbia. The greatest increases in basal and squamous cell carcinomas are on the head and neck. This indicates that exposure to sunlight is the major causative factor. The greatest increase in melanoma is on the trunk in men and on the lower limbs in women. The dramatic increases in nonmelanoma skin cancers in British Columbia, a relatively low sunlight area, suggest that major prevention programs are needed in areas that are not considered "sunspots." .A Gallagher RP; Ma B; McLean DI; Yang CP; Ho V; Carruthers JA; Warshawski LM. .I 275431 .U 91010018 .S J Am Acad Dermatol 9101; 23(3 Pt 1):422-8 .M Adult; Aged; Case Report; Histoplasmosis/*CO/PA; Human; HIV Infections/*CO; Male; Mouth Diseases/CO/PA; Opportunistic Infections/*CO/PA; Skin Diseases/*CO/PA; Support, Non-U.S. Gov't. .T Cutaneous lesions of disseminated histoplasmosis in human immunodeficiency virus-infected patients. .P JOURNAL ARTICLE. .W Disseminated histoplasmosis is being diagnosed more frequently in persons infected with the human immunodeficiency virus and is often the initial manifestation of the acquired immunodeficiency syndrome (AIDS). Disease-related cutaneous features of HIV-associated disseminated histoplasmosis are defined as mucocutaneous lesions from which fungal organisms were either cultured or demonstrated histopathologically. We report four HIV-seropositive patients with disseminated histoplasmosis who had culture-positive skin or oral lesions of histoplasmosis and review the specific cutaneous manifestations of HIV-associated disseminated histoplasmosis. Including our patients, disease-related skin and/or mucosal lesions were present in 11% of patients (26% of 239) with HIV-associated disseminated histoplasmosis. The possibility of disseminated histoplasmosis should be considered in all HIV-infected persons and in persons with AIDS risk factors who have fever, weight loss, hepatosplenomegaly, and new cutaneous lesions. An early skin or mucosal biopsy specimen for crushed tissue preparation, histologic evaluation, and fungal culture is a simple, rapid diagnostic procedure. .A Cohen PR; Bank DE; Silvers DN; Grossman ME. .I 275432 .U 91010019 .S J Am Acad Dermatol 9101; 23(3 Pt 1):429-40 .M Erythema/PC; Human; Photosensitivity Disorders/DI; Product Labeling; Skin/*RE; Sunlight/AE; Sunscreening Agents/*TU; Ultraviolet Rays/*/AE. .T A method for the determination of UVA protection for normal skin. .P JOURNAL ARTICLE. .W Although the UVB portion of the electromagnetic spectrum (290 to 320 nm) is responsible for most of the harmful effects of sunlight on the skin, wavelengths in the UVA region also contribute to photodamage. A simple and rapid clinical test, the sun protection factor determination, is available to assess the sunburn protective effect of a sunscreen, primarily a UVB effect. However, no practical test has been proposed to measure a sunscreen's UVA protection. We described a method for the calculation of UVA protection in normal subjects. The determination of UVA protection involves three steps: (1) the UV absorbance spectrum of the sunscreen on skin is determined spectrophotometrically; (2) a convolution spectrum is calculated by multiplying the solar spectrum with the Commission Internationale de l'Eclairage UV Hazard Spectrum; and (3) the sunscreen transmission spectrum is then incorporated into the convolution spectrum to obtain the UVA effectiveness ratio, which can be expressed as the UVA protection percentage. Because the UVA protection percentage value is based both on normal erythemic risk and on standard sunlight, the protection for any product can be easily measured. The procedure is simple, and values generated can be reproduced in other laboratories. .A Sayre RM; Agin PP. .I 275433 .U 91010020 .S J Am Acad Dermatol 9101; 23(3 Pt 1):440-4 .M Aged; Bowen's Disease/*PA/SU; Case Report; Human; Keratosis/*PA/SU; Male; Middle Age; Pigmentation Disorders/*PA/SU; Seborrhea/CO/PA; Skin Neoplasms/*PA/SU. .T Pigmented Bowen's disease arising from pigmented seborrheic keratoses. .P JOURNAL ARTICLE. .W We report three cases of pigmented Bowen's disease that clinically and histologically had features of seborrheic keratoses. We speculate about the mechanism of pigmentation in these lesions and suggest that they arise from pigmented seborrheic keratoses. .A Marschall SF; Ronan SG; Massa MC. .I 275434 .U 91010021 .S J Am Acad Dermatol 9101; 23(3 Pt 1):444-50 .M Adult; Case Report; Female; Human; Hydroxychloroquine/TU; Male; Melkersson-Rosenthal Syndrome/*/DT/PA/SU; Middle Age; Recurrence; Triamcinolone Acetonide/AD/TU. .T Cheilitis granulomatosa: report of six cases and review of the literature. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Six cases of cheilitis granulomatosa, a rare inflammatory disorder of unknown origin, are reported. The condition produces nontender, persistent swelling of one or both lips and affects primarily young adults. Histologically, nonnecrotizing granulomatous inflammation is seen. The clinical findings and results of therapy in these six cases are presented. One patient was treated with hydroxychloroquine sulfate (Plaquenil) that stabilized the process. One of our patients had vesicular-appearing lesions. Microscopic examination showed the lesions to be dilated superficial lymphatic channels, a finding that to our knowledge has not been previously described. .A Allen CM; Camisa C; Hamzeh S; Stephens L. .I 275435 .U 91010022 .S J Am Acad Dermatol 9101; 23(3 Pt 1):451-7 .M Adult; Aged; Case Report; Eosinophilia/*CI/PA; Fasciitis/PA; Female; Human; Kynurenine/UR; Middle Age; Myositis/PA; Prednisone/AD/TU; Scleroderma, Systemic/*CI/PA; Skin/PA; Syndrome; Tryptophan/AD/*AE/ME. .T Scleroderma and L-tryptophan: a possible explanation of the eosinophilia-myalgia syndrome. .P JOURNAL ARTICLE. .W Scleroderma developed in six women who were taking L-tryptophan. Fasciitis and morphea were most common, but one patient had pleural effusion, hypertension, and signs of cardiac and kidney failure. In five patients the biopsy findings were characteristic of scleroderma; the sixth patient had Crohn's disease and developed fasciitis; her biopsy specimen showed inflammatory arteritis. All patients' conditions improved after cessation of their L-tryptophan intake, initiation of corticosteroid therapy, or both. These findings confirm previous data that show altered tryptophan-kynurenine metabolism in some patients with scleroderma and fasciitis, particularly with tryptophan loading. .A Connolly SM; Quimby SR; Griffing WL; Winkelmann RK. .I 275436 .U 91010023 .S J Am Acad Dermatol 9101; 23(3 Pt 1):458-62 .M Administration, Cutaneous; Biological Availability; Chromatography, High Pressure Liquid; Comparative Study; Emollients/PD/*PK; Female; Human; Hydrocortisone/PD/*PK; Male; Radioimmunoassay; Skin/DE/*ME. .T Correlation between the drug penetration and the blanching effect of topically applied hydrocortisone creams in human beings. .P JOURNAL ARTICLE. .W Two topical formulations of 2.5% hydrocortisone were tested to investigate the possible correlation between the blanching response of topically applied hydrocortisone and its release from the formulation after its penetration into the stratum corneum. After application of the cream, the stratum corneum was removed at different intervals and the hydrocortisone content was measured by radioimmunoassay. The blanching responses (expressed as mean score vs time) showed a 1.5-fold difference (significant at p = 0.0026) between the two creams at the maximum effect, which was reached for both creams after 16 hours. The amounts of hydrocortisone present in the stratum corneum after every application period showed a twofold difference (p = 0.0001) between the two creams. However, in contrast to the blanching, these quantities remained constant from 4 to 24 hours. This steady state characteristic may be partially due to the use of occlusion and to the excess formulation remaining at the surface. Although there is no parallelism with time between the results of the two methods, both give clear evidence of a difference in stratum corneum penetration and pharmacologic activity of the two formulations. Drug penetrations and pharmacodynamic activities of the two creams can be correlated with in vitro release characteristics. .A Caron D; Queille-Roussel C; Shah VP; Schaefer H. .I 275437 .U 91010024 .S J Am Acad Dermatol 9101; 23(3 Pt 1):462-9 .M Adult; Female; Flutamide/AD/*TU; Hirsutism/BL/*DT; Human; Sex Hormones/BL. .T Treatment of hirsutism with the pure antiandrogen flutamide. .P JOURNAL ARTICLE. .W The effectiveness of the antiandrogen flutamide in combination with an oral contraceptive was studied in 20 patients with moderate to severe hirsutism. Eight patients had no previous therapy, whereas 12 had failed to respond to oral contraceptives, spironolactone, or dexamethasone therapy. Treatment with the antiandrogen flutamide (250 mg twice daily) and an oral contraceptive (Ortho 1/35) resulted in a particularly rapid and marked decrease in the total hirsutism score, which reached the normal range at 7 months. Seborrhea, acne, and hair loss score were also rapidly corrected. Treatment was associated with a decrease in plasma luteinizing hormone, progesterone, and estradiol levels. Plasma sex hormone-binding globulin levels were initially low in 18 to 20 patients but increased significantly during therapy. No clinically significant side effects were observed. .A Cusan L; Dupont A; Belanger A; Tremblay RR; Manhes G; Labrie F. .I 275438 .U 91010025 .S J Am Acad Dermatol 9101; 23(3 Pt 1):470-2 .M Administration, Cutaneous; Adolescence; Adult; Alopecia/*DT; Dinoprostone/*AA/AD/TU; Double-Blind Method; Hair/GD; Human; Male; Middle Age; Random Allocation; Support, Non-U.S. Gov't. .T Transdermal viprostol in the treatment of male pattern baldness. .P JOURNAL ARTICLE. .W Fifty-seven men were randomly assigned for treatment of androgenetic alopecia with viprostol, vehicle, or placebo twice daily for 24 weeks. Nonvellus hair growth was assessed subjectively by both patient and investigator and objectively through hair counts from macrophotographs of the target area. Nonvellus target area hair counts declined in all three treatment groups at the end of the 6-month study. Viprostol is not an effective hair growth promoter in androgenetic alopecia. .A Olsen EA; DeLong E. .I 275439 .U 91010026 .S J Am Acad Dermatol 9101; 23(3 Pt 1):473-8 .M Acute Disease; Adolescence; Child; Child, Preschool; Chronic Disease; Female; Follow-Up Studies; Human; Infant; Male; Pityriasis/*CL/ET/PA/RA; Ultraviolet Therapy. .T Pityriasis lichenoides in children: a long-term follow-up of eighty-nine cases. .P JOURNAL ARTICLE. .W Pityriasis lichenoides is usually classified into an acute and a chronic form. From a review of 89 cases of the disease seen since 1974 it seems that a more realistic classification into three main groups, according to the distribution of pityriasis lichenoides lesions, could be made, namely, a diffuse, a central, and a peripheral form, each characterized by a different clinical course. Conversely, no correlations were detected in our series between the severity of skin lesions and their distribution or the overall course of the disease. None of our cases suggests the possible evolution of pityriasis lichenoides into lymphomatoid papulosis. Although no infectious causative agent has been identified, a viral origin seems likely in some cases. Most patients responded favorably to UVB irradiation. Our conclusions are (1) that pityriasis lichenoides is probably a clinical disorder with a diverse etiology and (2) that its classification by distribution seems more useful than its subdivision into an acute and a chronic form. .A Gelmetti C; Rigoni C; Alessi E; Ermacora E; Berti E; Caputo R. .I 275440 .U 91010027 .S J Am Acad Dermatol 9101; 23(3 Pt 1):479-83 .M Adult; Benzoates/*AE/CH; Dermatitis, Contact/*ET; Female; Gels; Human; Male; Middle Age; Patch Tests/MT; Photosensitivity Disorders/*CI; Piroxicam/AD/*AE/CH; Thimerosal/IM. .T Piroxicam-induced photosensitivity and contact sensitivity to thiosalicylic acid. .P JOURNAL ARTICLE. .W A photocontact dermatitis developed in three patients after the application of gel containing 0.5% piroxicam. Patch tests were positive to thiomersal and thiosalicylic acid. Photopatch tests with piroxicam at several concentrations were positive in the three patients but negative in 62 normal volunteer subjects. Patch tests performed on 14 patients with proved systemic photosensitivity to piroxicam were positive for thiomersal and thiosalicylic acid. Nine of 12 patients previously sensitized to thiosalicylic acid and with no history of exposure to piroxicam showed positive photopatch test reactions to this chemical. These results support a relation between piroxicam-induced photosensitivity and contact sensitivity to thiosalicylic acid. Contact allergic sensitivity to the latter is a marker for patients with a high risk of developing photosensitivity reactions to piroxicam. These reactions may be due to photoproducts of the drug rather than metabolites. .A Serrano G; Bonillo J; Aliaga A; Cuadra J; Pujol C; Pelufo C; Cervera P; Miranda MA. .I 275441 .U 91010029 .S J Am Acad Dermatol 9101; 23(3 Pt 1):487-9 .M Adult; Aged; Female; Follow-Up Studies; Granuloma/*DT; Human; Hydroxychloroquine/AD/*TU; Male; Middle Age; Sarcoidosis/*DT; Skin Diseases/*DT. .T Hydroxychloroquine is effective therapy for control of cutaneous sarcoidal granulomas. .P JOURNAL ARTICLE. .W Cutaneous sarcoidosis often responds poorly to topical and intralesional corticosteroids but may respond to moderate to high doses of oral corticosteroids. To avoid the use of systemic corticosteroids, we treated 17 patients with cutaneous sarcoidal granulomas with hydroxychloroquine (2 to 3 mg/kg/day) in an open clinical trial. If response occurred, other medications were first tapered and then the hydroxychloroquine dosage was reduced or stopped. The cutaneous lesions of 12 patients regressed within 4 to 12 weeks, and they were able to stop other therapies; three patients had a partial response, and two patients had no regression. Two of eight patients with pulmonary sarcoidosis improved. No ocular toxicity was noted. .A Jones E; Callen JP. .I 275442 .U 91010030 .S J Am Acad Dermatol 9101; 23(3 Pt 1):489-93 .M Adult; Aged; Aged, 80 and over; Facial Dermatoses/RT/SU; Female; Human; Keratoacanthoma/*RT/SU; Lip Diseases/RT/SU; Male; Middle Age; Recurrence; Skin Diseases/*RT/SU. .T Treatment of aggressive keratoacanthomas by radiotherapy. .P JOURNAL ARTICLE. .W Keratoacanthomas infrequently are treated by radiotherapy. However, keratoacanthomas that are recurrent after surgical excision or whose resection would result in cosmetic deformity may benefit from radiotherapy. Between January 1970 and June 1988, 29 such keratoacanthomas in 18 patients were irradiated. Doses ranged from 3500 cGy in 15 fractions to 5600 cGy in 28 fractions. Measured end points of therapy were (1) initial response, (2) freedom from recurrence, and (3) quality of the subsequent cosmetic appearance (scored as good, fair, or poor). No lesion progressed and all eventually regressed completely. Cosmetic results generally were considered good by both the patient and the referring dermatologist; none of the results was considered poor. Our results demonstrate that radiation is an effective means of treating keratoacanthomas. .A Donahue B; Cooper JS; Rush S. .I 275443 .U 91010031 .S J Am Acad Dermatol 9101; 23(3 Pt 1):494-8 .M Bone Diseases/*CO; Human; Osteomyelitis/CO; Skin Diseases/*CO. .T Dermatoses associated with sterile lytic bone lesions. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W In recent years several dermatoses, palmoplantar pustulosis, acne fulminans, and Sweet's syndrome, have been associated with sterile lytic bone lesions. This article discusses the clinical, laboratory, and histologic findings of these disorders and postulates a common mechanism underlying the bone lesions. .A Sofman MS; Prose NS. .I 275444 .U 91010032 .S J Am Acad Dermatol 9101; 23(3 Pt 1):498-502 .M Adult; Aged; Aged, 80 and over; Female; Human; Male; Middle Age; Myasthenia Gravis/CO/EP; Neoplasms/*CO/EP; Pemphigus/*CO/EP; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Thymus Neoplasms/*CO/EP. .T The relationship of pemphigus to neoplasia. .P JOURNAL ARTICLE; REVIEW; REVIEW OF REPORTED CASES. .W A statistically increased incidence of malignancy has been observed in patients with pemphigus. A review of the literature reveals 42 cases of nonthymic malignancies and 18 cases of thymic malignancies. A significant predominance of men, with mean age at onset of 50 years, was observed. Pemphigus vulgaris is more common in patients with nonthymic neoplasms, whereas pemphigus foliaceus or pemphigus erythematosus and pemphigus vulgaris are equally common in patients with thymic neoplasms. Lymphoreticular malignancies, especially Kaposi's sarcoma, are most frequently observed. The majority of patients with nonthymic neoplasms have pemphigus before the detection of the malignancy and have a favorable 5-year survival rate after tumor resection. The majority of the patients with thymic neoplasms have a thymoma before the development of pemphigus. In some patients pemphigus develops after thymectomy and myasthenia gravis is often associated. Overall, 37 of the 60 patients, or 61%, had a neoplasm of the immune system. .A Younus J; Ahmed AR. .I 275445 .U 91010033 .S J Am Acad Dermatol 9101; 23(3 Pt 1):503-7 .M Adult; Aged; Aged, 80 and over; Female; Follow-Up Studies; Human; Male; Middle Age; Neutrophils/*PA; Prednisolone/TU; Recurrence; Scotland/EP; Skin Diseases/DT/EP/*PA; Syndrome. .T Sweet's syndrome: a clinicopathologic review of twenty-nine cases. .P JOURNAL ARTICLE. .W Twenty-nine patients with Sweet's syndrome were studied. Not all of Sweet's original criteria were necessarily present and diagnosis was dependent on the recognition of the typical, acute, tender, erythematous plaques and the characteristic histologic features of a neutrophilic infiltrate with leukocytoclasis. Women are affected much more frequently than men. The origin of Sweet's syndrome is still unclear, but an underlying disease was found in more than 50% of our cases. A streptococcal infection was evident in six cases, inflammatory bowel disease in three cases, malignancy in four cases, and pregnancy in two others. Treatment with oral prednisolone for an average of 6 weeks was the usual treatment, although in four patients the disease cleared spontaneously. Resolution of the eruption is occasionally followed by milia and scarring. Recurrences are common and affect up to one third of patients. .A Kemmett D; Hunter JA. .I 275446 .U 91010034 .S J Am Acad Dermatol 9101; 23(3 Pt 1):508-12 .M Dermatology/*; Medical Records Systems, Computerized/*; Microcomputers; Software; Surgery/*; Time Factors. .T Computer-generated operative reports. How to save up to 30 minutes per day. .P JOURNAL ARTICLE. .A Swinehart JM. .I 275447 .U 91010035 .S J Am Acad Dermatol 9101; 23(3 Pt 1):513-4 .M Biopsy; Diagnosis, Differential; Histological Techniques; Human; Scleroderma, Circumscribed/*PA; Skin/DE. .T Dramatic tissue artifact that mimics morphea or scleroderma. .P JOURNAL ARTICLE. .A Stanton O; LeBoit PE. .I 275448 .U 91010036 .S J Am Acad Dermatol 9101; 23(3 Pt 1):514-5 .M Adult; Case Report; Human; Injections, Intramuscular; Male; Penicillin G/AD/TU; Skin/*PA; Syphilis/DT/*PA. .T Occult primary syphilis: the nonerosive chancre. .P JOURNAL ARTICLE. .A Sperling LC; Hicks K; James WD. .I 275449 .U 91010037 .S J Am Acad Dermatol 9101; 23(3 Pt 1):515-6 .M Acrodermatitis/*DT; Aged; Case Report; Cell Division/DE; Cyclosporins/AD/*TU; Hand Dermatoses/DT/PA; Human; Keratinocytes/ME; Male; Psoriasis/*DT/PA. .T Acrodermatitis continua-type of pustular psoriasis responds to low-dose cyclosporine. .P JOURNAL ARTICLE. .A Peter RU; Ruzicka T; Donhauser G; Braun-Falco O. .I 275450 .U 91010038 .S J Am Acad Dermatol 9101; 23(3 Pt 1):516-8 .M Human; Mass Screening; Melanoma/DI/MO/*PC; Questionnaires; Rhode Island/EP; Risk Factors; Skin Neoplasms/DI/MO/*PC. .T Prevalence of the early warning signs of melanoma among participants in the 1989 Rhode Island skin cancer screening. .P JOURNAL ARTICLE. .A Weinstock MA. .I 275451 .U 91010039 .S J Am Acad Dermatol 9101; 23(3 Pt 1):518-9 .M Aged; Aged, 80 and over; Biopsy; Case Report; Female; Human; Mouth Mucosa/PA; Palatal Neoplasms/EP/*PA/RT; Palate/*PA; Sarcoma, Kaposi's/EP/*PA/RT. .T Primary oral Kaposi's sarcoma of the hard palate. .P JOURNAL ARTICLE. .A Searles GE; Markman S; Yazdi HM. .I 275452 .U 91010040 .S J Am Acad Dermatol 9101; 23(3 Pt 1):519-20 .M Adult; Arachnoid Cysts/*CO; Basal Cell Nevus Syndrome/*CO/SU; Brain/PA; Case Report; Human; Magnetic Resonance Imaging; Male; Migraine/DI/ET; Skin Neoplasms/SU. .T Arachnoid cyst in a patient with basal cell nevus syndrome. .P JOURNAL ARTICLE. .A Pearlman RL; Herzog JL. .I 275453 .U 91010041 .S J Am Acad Dermatol 9101; 23(3 Pt 1):520-2 .M Biopsy; Case Report; Cell Transformation, Neoplastic/*PA; Helper Cells/IM; Human; Keratosis/*PA; Lymphoma, T-Cell, Cutaneous/*PA; Male; Middle Age; Sezary Syndrome/*PA; Skin/PA; Skin Neoplasms/*PA. .T Transformation of Sezary syndrome and the sign of Leser-Trelat: a histopathologic study. .P JOURNAL ARTICLE. .A Wieselthier JS; Bhawan J; Koh HK. .I 275454 .U 91010042 .S J Am Acad Dermatol 9101; 23(3 Pt 1):522-3 .M Aged; Biopsy; Case Report; Fluorescent Antibody Technique; Human; Male; Pemphigus/DT/*PA; Recurrence; Skin/*PA. .T Pemphigus vulgaris presenting as a nodular lesion. .P JOURNAL ARTICLE. .A Ohta M; Yamamoto M; Utani A; Ohno S; Danno K. .I 275455 .U 91010043 .S J Am Acad Dermatol 9101; 23(3 Pt 1):523-5 .M Administration, Topical; Case Report; Homosexuality; Human; HIV Infections/*CO; Male; Middle Age; Mouth Mucosa/PA; Recurrence; Stomatitis, Aphthous/CO/*DT/PA; Thalidomide/AD/*TU. .T Recurrent aphthous ulcer in patient infected with human immunodeficiency virus: successful treatment with thalidomide. .P JOURNAL ARTICLE. .A Radeff B; Kuffer R; Samson J. .I 275456 .U 91010044 .S J Am Acad Dermatol 9101; 23(3 Pt 1):525-6 .M Cholecalciferols/*BI/BL; Erythema/ET; Female; Human; Male; Photosynthesis/*RE; Skin Pigmentation/PH/*RE; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Ultraviolet Rays/AE. .T Skin types and epidermal photosynthesis of vitamin D3. .P JOURNAL ARTICLE. .A Matsuoka LY; Wortsman J; Haddad JG; Hollis BW. .I 275457 .U 91010045 .S J Am Acad Dermatol 9101; 23(3 Pt 1):526-7 .M Aged; Biopsy; Case Report; Etretinate/AD/*AE/TU; Human; Keratosis/*CI/PA; Male; Pityriasis Rubra Pilaris/DT/*PA; Prednisone/AD/TU. .T Dramatic follicular plugging in pityriasis rubra pilaris. .P JOURNAL ARTICLE. .A Koehn GG. .I 275458 .U 91010046 .S J Am Acad Dermatol 9101; 23(3 Pt 1):528-9 .M Dermatology/ED/*ST; Education, Medical/*ST. .T Qualifications of the provider. .P JOURNAL ARTICLE. .A Frankel EB. .I 275459 .U 91010047 .S J Am Acad Dermatol 9101; 23(3 Pt 1):530 .M Human; Naltrexone/*AA/AD/AE/TU; Pruritus/*DT; Random Allocation. .T Nalmefene and pruritus [letter; comment] .P COMMENT; LETTER. .A Harrison PV. .I 275460 .U 91010048 .S J Am Acad Dermatol 9101; 23(3 Pt 1):530 .M Carcinoma, Squamous Cell/*CO/SU; Human; Lung Neoplasms/*CO/SU; Male; Pemphigus/*CO. .T Pemphigus vulgaris and squamous cell carcinoma of the lung [letter; comment] .P COMMENT; LETTER. .A Lynfield YL. .I 275461 .U 91010049 .S J Am Acad Dermatol 9101; 23(3 Pt 1):530-2 .M Case Report; Female; Hand Dermatoses/*PA; Human; Mucins/*; Skin/PA; Skin Diseases/*PA. .T Acral persistent papular mucinosis: a distinct entity [letter; comment] .P COMMENT; LETTER. .A Rongioletti F; Rebora A; Crovato F. .I 275462 .U 91010050 .S J Am Acad Dermatol 9101; 23(3 Pt 1):532 .M Case Report; Female; Human; Keratoacanthoma/*ET; Lupus Erythematosus, Discoid/*CO; Skin/UL; Skin Diseases/*ET. .T Discoid lupus erythematosus [letter; comment] .P COMMENT; LETTER. .A Huntley AC. .I 275463 .U 91010051 .S J Am Acad Dermatol 9101; 23(3 Pt 1):532-3 .M Chronic Disease; Dermatitis Medicamentosa/*; Dermatitis, Contact/*; Human; Pemphigus/*GE. .T Familial benign chronic pemphigus (Hailey-Hailey disease) and contact allergies [letter; comment] .P COMMENT; LETTER. .A de Wit FS. .I 275464 .U 91010052 .S J Am Acad Dermatol 9101; 23(3 Pt 1):533-6 .M Alprostadil/ME; Dermatitis, Atopic/*ME; Dinoprostone/ME; Female; Human; IgE/BI; Infant; Linoleic Acids/*ME; Milk, Human. .T Deficient conversion of linoleic acid [letter; comment] .P COMMENT; LETTER. .A Wright S; Horrobin D; Manku M. .I 275465 .U 91010053 .S J Am Acad Dermatol 9101; 23(3 Pt 2):549-51 .M Antifungal Agents/*TU; Dermatomycoses/*DT; Human. .T Treatment of fungal skin infections: state of the art. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W The number of cases of mycotic infections are increasing, presenting physicians today with an unprecedented challenge in handling the treatment and prophylactic control of these disorders. The increase in mycotic disorders is due to many factors, such as longer life span, organ transplantation, and the acquired immunodeficiency syndrome. The pharmaceutical industry is providing physicians with newer, more potent drugs to manage mycoses. An overview of current practice in the use of topical and oral agents, especially ketoconazole, are given in the following specific mycoses: tinea capitis, pityriasis versicolor, seborrheic dermatitis, Trichophyton rubrum infections, vaginal candidiasis, and moist intertriginous tineas. The efficacy of ketoconazole in various vehicles and dosage schedules and of traditional agents such as griseofulvin are discussed with relation to each of the mycoses. .A Jacobs PH. .I 275466 .U 91010054 .S J Am Acad Dermatol 9101; 23(3 Pt 2):549-614 .M Antifungal Agents/*TU; Human; Ketoconazole/*AA/TU; Mycoses/*DT; Support, Non-U.S. Gov't. .T Clinical use of itraconazole in fungal infections. .P OVERALL. .I 275467 .U 91010055 .S J Am Acad Dermatol 9101; 23(3 Pt 2):551-4 .M Antifungal Agents/AE/*TU; Human; Ketoconazole/*AA/AE/TU; Tinea Versicolor/*DT. .T Itraconazole in tinea versicolor: a review. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Itraconazole, a new orally active triazole antifungal, has been tested in patients with pityriasis versicolor. A number of studies have shown that itraconazole is effective for this mild fungal skin disease. The total dose required for effective treatment is 1000 mg, and it has been given as 200 mg for 5 days or 7 days. The organisms disappear slowly from the skin, even when dead, and the results should be assessed clinically and mycologically at around 3 to 4 weeks after treatment. Numerous studies have shown that itraconazole is superior to placebo and as effective as selenium sulfide, clotrimazole, and ciclopirox olamine. It is also better tolerated by patients than selenium sulfide. .A Delescluse J. .I 275468 .U 91010056 .S J Am Acad Dermatol 9101; 23(3 Pt 2):554-8 .M Antifungal Agents/AE/PK/*TU; Dermatomycoses/*DT; Drug Administration Schedule; Human; Ketoconazole/*AA/AE/PK/TU. .T Itraconazole in common dermatophyte infections of the skin: fixed treatment schedules. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Itraconazole is an effective medication against the most common dermatophytoses. It has been shown to be more active than griseofulvin and ketoconazole. Ease of use, affinity for keratinized tissues, lack of toxicity, continued activity after discontinuation, and the possibility of using fixed schedules are advantages of itraconazole. The fixed schedules indicated by pharmacokinetics and clinical studies are one 100 mg capsule daily for 15 days in cases of tinea corporis and tinea cruris and the same dosage for 30 days in cases of tinea pedis and tinea manuum. These fixed treatments have some limitations, and they are not recommended for treating tinea capitis and tinea unguium. The drug is well tolerated. .A Saul A; Bonifaz A. .I 275469 .U 91010057 .S J Am Acad Dermatol 9101; 23(3 Pt 2):559-60 .M Antifungal Agents/*TU; Child; Female; Follow-Up Studies; Human; Ketoconazole/*AA/TU; Male; Tinea Capitis/*DT/MI. .T Itraconazole in the treatment of tinea capitis. .P JOURNAL ARTICLE. .W Fifty patients with tinea capitis were treated with itraconazole, 25 to 100 mg/day, for 20 to 73 days in six countries. Forty-seven patients (94%) responded clinically (healed or markedly improved) to therapy, of which 38 patients (76%) completely healed and 9 patients (18%) markedly improved. Three patients (6%) failed therapy. Forty-two patients were assessable for mycologic examination; 38 patients (93%) converted mycologically to negative and 4 patients (7%) remained positive for organisms. In one group of 20 patients treated for 30 days, 6 patients were clinically and mycologically healed. By the 2-week follow-up visit 9 additional patients were healed, and 4 weeks after treatment all 20 patients were both clinically and mycologically healed. The primary organisms reported were Microsporum canis and Trichophyton tonsurans. Only one patient reported a possible side effect (tired legs). Laboratory values were all within normal limits, except for one patient who had a transient and slight increase in serum transaminase level. Low-dose itraconazole appears to be safe and effective in the treatment of tinea capitis. .A Legendre R; Esola-Macre J. .I 275470 .U 91010058 .S J Am Acad Dermatol 9101; 23(3 Pt 2):561-4 .M Adult; Aged; Antifungal Agents/AE/*TU; Chronic Disease; Dermatomycoses/*DT; Drug Administration Schedule; Female; Fingers; Foot Dermatoses/DT; Hand Dermatoses/DT; Human; Ketoconazole/*AA/AE/TU; Male; Middle Age; Toes. .T Itraconazole in the management of chronic dermatophytosis. .P JOURNAL ARTICLE. .W Fifty-five patients with griseofulvin-unresponsive dermatophytosis caused by Trichophyton rubrum were treated with itraconazole. They had either tinea corporis or "dry type" infections of the palms, soles, or nails. The following sites were affected: trunk (12 infections), soles (47), toe webs (52), palms (26), fingernails (29), and toenails (42). Patients were treated with oral itraconazole until clinical and mycologic remission were achieved. Response rates and mean times to recovery were as follows: trunk, 100%, 1.5 months; soles, 83%, 6.7 months; toe webs, 90%, 7.2 months; palms, 96%, 4.6 months; fingernails, 90%, 5.4 months; and toenails, 76%, 10.3 months). In a 6-month follow-up period 7 of 30 patients with toenail infections who had responded to treatment had a clinical and mycologic relapse, usually of one nail. Side effects were minimal but included abdominal discomfort (three patients), headache (one), and weight gain (two). No persistent abnormalities in blood biochemistry were seen, even in patients who received itraconazole for more than 9 months. .A Hay RJ; Clayton YM; Moore MK; Midgely G. .I 275471 .U 91010059 .S J Am Acad Dermatol 9101; 23(3 Pt 2):565-7 .M Antifungal Agents/*TU; Candidiasis, Oral/*DT; Human; Ketoconazole/*AA/TU. .T Treatment of oral candidosis with itraconazole: a review. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Oral candidosis is a common infection in infants, elderly persons, patients receiving immunosuppressive therapy, and patients with acquired immunodeficiency syndrome (AIDS). The orally active antifungal agent itraconazole has been evaluated in a number of different patient populations with oral and oropharyngeal candidosis. Initial studies have shown that itraconazole, 100 or 200 mg/day for 14 days, is more active than placebo in treating oral candidosis. A comparative study between itraconazole capsules (200 mg once daily) and clotrimazole troches (10 mg five times daily) showed equivalent results at the end of therapy but a significantly faster response to itraconazole and a faster relapse rate with clotrimazole. A study in AIDS patients with oropharyngeal candidosis demonstrated that itraconazole, 200 mg/day, and ketoconazole, 400 mg day, for 4 weeks give equivalent clinical cure rates and similar relapse rates. A pilot study with an oral solution of itraconazole has given an impressive 100% clinical and mycological response rate within 1 week of treatment. In conclusion, itraconazole in capsule or in solution form may constitute a major addition to the armamentarium of drugs against oropharyngeal candidosis. .A Blatchford NR. .I 275472 .U 91010060 .S J Am Acad Dermatol 9101; 23(3 Pt 2):568-72 .M Administration, Intravaginal; Administration, Oral; Antifungal Agents/*AD; Candidiasis, Vulvovaginal/*DT; Female; Human; Pregnancy; Pregnancy Complications, Infectious/DT; Recurrence; Sexual Partners. .T Treatment of vaginal candidiasis: orally or vaginally? .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Vaginal candidiasis continues to be the most common cause of vaginal discharge. A large variety of topical drugs and a selection of orally active antifungals are currently available. The choice between the use of oral drugs or intravaginal agents will depend on the therapeutic results obtained with the different agents, side effects, pregnancy status, and patient preference. The results obtained in the Maria Hospital, Tilburg, The Netherlands, and a review of foreign data suggest the following: (1) For acute infection oral and topical agents produce equivalent results. (2) For chronic infections oral medication is preferred. (3) Oral therapy should not be given to pregnant patients or to patients not using reliable contraceptive measures. (4) Half the patients prefer oral medication; only 5% prefer intravaginal therapy, and the others had no clear preference. .A Merkus JM. .I 275473 .U 91010061 .S J Am Acad Dermatol 9101; 23(3 Pt 2):572-6 .M Administration, Intravaginal; Administration, Oral; Antifungal Agents/*AD; Candidiasis, Vulvovaginal/*DT; Drug Administration Schedule; Female; Human. .T Individualizing treatment of vaginal candidiasis. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Clinicians have a vast array of effective antimycotics for the treatment of vaginal candidiasis. Multiple topical formulations are available, yet there is little evidence to suggest that formulation per se influences outcome. A growing number of highly effective oral systemic antimycotic agents provide the practitioner with additional options. Treatment regimens have also changed with the introduction of shorter, often single-day/single-dose courses of therapy. Not all therapeutic agents have the same activity against vaginal fungal pathogens in that topical azoles tend to be more active than nystatin. Differences in patient characteristics, however, are more important than the differences between antimycotic agents and therapeutic regimens in determining selection of the appropriate antimycotic. Patients with vaginal candidiasis vary with regard to duration and severity of symptoms and past frequency of attacks, distribution of inflammation, and pregnancy status. The clinician should consider all these variables both in selecting the appropriate antimycotic agent and the route of administration and in planning the duration of therapy. Individualized therapy offers additional benefits to patients, who may then enjoy the maximum advantages of antimycotics now available. .A Sobel JD. .I 275474 .U 91010062 .S J Am Acad Dermatol 9101; 23(3 Pt 2):577-86 .M Adult; Aged; Antifungal Agents/AE/*TU; Child; Child, Preschool; Drug Administration Schedule; Female; Human; Ketoconazole/*AA/AE/TU; Male; Microbial Sensitivity Tests; Middle Age; Mycoses/*DT/MI. .T Itraconazole treatment of phaeohyphomycosis. .P JOURNAL ARTICLE. .W Nineteen patients with phaeohyphomycosis were treated with itraconazole. Of these, 17 were assessable for clinical outcome. Of these, two had received no prior therapy, five had failed amphotericin B therapy, four had failed ketoconazole or miconazole therapy, and five had failed both amphotericin B and azole therapy. One patient had received only prior surgical intervention. Fungi of seven different genera caused disease of the skin in nine patients, soft tissue in nine, sinuses in eight, bone in five, joints in two, and lungs in two. Itraconazole was given in dosages ranging from 50 to 600 mg/day for 1 to 48 months. Clinical improvement or remission occurred in nine patients. Two patients have had stabilization of disease. Six patients failed treatment, one had a relapse after initially successful treatment. Itraconazole appears to be highly effective in some patients with phaeohyphomycosis, including patients refractory to other antifungal agents. .A Sharkey PK; Graybill JR; Rinaldi MG; Stevens DA; Tucker RM; Peterie JD; Hoeprich PD; Greer DL; Frenkel L; Counts GW; et al. .I 275475 .U 91010063 .S J Am Acad Dermatol 9101; 23(3 Pt 2):587-93 .M Antifungal Agents/*TU; Aspergillosis/DT; Child; Cryptococcosis/DT; Drug Administration Schedule; Human; Ketoconazole/*AA/TU; Mycoses/DI/*DT; Patient Compliance; Recurrence; Remission Induction; Sporotrichosis/DT; Support, Non-U.S. Gov't. .T European experience with itraconazole in systemic mycoses. .P JOURNAL ARTICLE. .W Since January 1985 more than 100 patients with deep fungal infections have been treated with itraconazole (200 to 400 mg/day) in Northern Italy. Evaluation of the drug efficacy and tolerance was possible in one patient with sporotrichosis, in 34 with aspergillosis, and in 36 with cryptococcosis (mainly patients positive for human immunodeficiency virus). Response to itraconazole alone was obtained in the case of sporotrichosis and in 24 of 34 patients with different forms of aspergillosis (of the 18 patients with invasive pulmonary aspergillosis, 15 were cured). Patients with cryptococcosis received itraconazole for active infection and/or for prevention of relapse. Active infection was treated successfully with itraconazole alone in 9 of 12 patients and with itraconazole plus flucytosine in 8 of 10 patients. Of the 31 patients who received itraconazole maintenance therapy for up to 27 months, 4 (13%) had relapses; 14 (45%) did not have relapses, and decline of serum antigen was detected in 12 of them; and 13 (42%) were completely cured (serum antigen titer dropped to zero). With the exception of hypokalemia in one patient, itraconazole was well tolerated even in patients who received the drug for several months or years. .A Viviani MA; Tortorano AM; Pagano A; Vigevani GM; Gubertini G; Cristina S; Assaisso ML; Suter F; Farina C; Minetti B; et al. .I 275476 .U 91010064 .S J Am Acad Dermatol 9101; 23(3 Pt 2):593-601 .M Adolescence; Adult; Aged; Antifungal Agents/AE/PK/*TU; Chronic Disease; Coccidioides/DE; Coccidioidomycosis/*DT/MI; Drug Administration Schedule; Female; Human; Ketoconazole/*AA/AE/PK/TU; Male; Microbial Sensitivity Tests; Middle Age; Recurrence. .T Itraconazole therapy for nonmeningeal coccidioidomycosis: clinical and laboratory observations. .P JOURNAL ARTICLE. .W Itraconazole, a new oral triazole antifungal agent, was administered in 75 courses to patients with chronic coccidioidomycosis at dosages of 50 to 400 mg/day for a median duration of 10 months. Assessment of efficacy was made with a standardized scoring system. Responses were seen in 42 of 58 assessable courses (72%). Nonresponse occurred exclusively in patients who had failed previous therapy and was most common in pulmonary disease. Toxicity was minimal at the doses studied. Pharmacokinetic analysis of itraconazole in serum at steady state showed negligible circadian variation; differences in serum concentrations among patients were large. Clinical isolates of Coccidioides immitis showed uniform in vitro susceptibility to itraconazole. Itraconazole shows impressive activity in this series of patients with refractory coccidioidomycosis. Further evaluation of itraconazole in this and in other systemic mycoses is in order. .A Tucker RM; Denning DW; Arathoon EG; Rinaldi MG; Stevens DA. .I 275477 .U 91010065 .S J Am Acad Dermatol 9101; 23(3 Pt 2):602-7 .M Acquired Immunodeficiency Syndrome/CO/MO; Antifungal Agents/AE/*TU; Antigens, Fungal/AN; Aspergillosis/*DT/ET; Aspergillus/DE; Cryptococcosis/*DT/ET; Cryptococcus/IM; Human; Ketoconazole/*AA/AE/TU; Microbial Sensitivity Tests; Opportunistic Infections/*DT/ET; Organ Transplantation/AE; Recurrence; Survival Rate. .T Itraconazole in opportunistic mycoses: cryptococcosis and aspergillosis. .P JOURNAL ARTICLE. .W Striking results were obtained with oral itraconazole therapy in two opportunistic mycoses. Of 28 patients with cryptococcal meningitis, 18 achieved complete responses, including 16 of 24 patients with acquired immunodeficiency syndrome. Other manifestations of cryptococcosis were similarly responsive. In aspergillosis 12 of 15 patients responded, including 8 of 10 immunocompromised hosts. These patients included those with invasive pulmonary disease (4/5), skeletal disease (2/2), pleural disease (1/2), and pericardial, sinus, mastoid, hepatosplenic, or nail disease (1/1). These results with itraconazole compare favorably to conventional (parenteral) therapy, and toxicity was minimal. This suggests that comparative trials are now in order. .A Denning DW; Tucker RM; Hanson LH; Stevens DA. .I 275478 .U 91010066 .S J Am Acad Dermatol 9101; 23(3 Pt 2):607-14 .M Adult; Aged; Antifungal Agents/*TU; Aspergillosis/*DT; Chronic Disease; Drug Administration Schedule; Encephalitis/DT; Female; Human; Ketoconazole/*AA/TU; Lung Diseases, Fungal/DT; Male; Maxillary Sinusitis/DT; Middle Age; Recurrence. .T Itraconazole therapy in aspergillosis: study in 49 patients. .P CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY. .W Itraconazole, 200 to 400 mg once daily, was administered to 49 patients with different types of aspergillosis: pulmonary aspergilloma (14 patients), chronic necrotizing pulmonary aspergillosis (14), and invasive aspergillosis (21). Itraconazole was prescribed alone or in combination or after treatment with amphotericin B and flucytosine. Of 14 aspergilloma patients, 2 were cured and 8 had symptomatic improvement. In chronic necrotizing pulmonary aspergillosis, 7 of 14 patients were cured and 6 improved significantly. In invasive aspergillosis treatment failed in 6 patients and 15 were cured. Itraconazole can be an alternative to amphotericin B in the treatment of invasive aspergillosis and chronic necrotizing pulmonary aspergillosis. In aspergilloma itraconazole may be useful in inoperable cases. .A Dupont B. .I 275479 .U 91010256 .S J Am Dent Assoc 9101; 121(3):315-6, 318 .M Case Report; Communicable Disease Control/*; Dentists/*; Disposable Equipment; Gloves, Surgical; Hepatitis B/PC/*TM; Human; Male; Middle Age; Pennsylvania. .T Hepatitis developments [letter; comment] .P COMMENT; LETTER. .A Carter SD. .I 275480 .U 91010257 .S J Am Dent Assoc 9101; 121(3):322-3, 325, 328 .M Dental Implantation/*; Human; Specialties, Dental/*; Specialty Boards. .T Implantology. Does it merit specialty status? .P JOURNAL ARTICLE. .A McCann D. .I 275481 .U 91010258 .S J Am Dent Assoc 9101; 121(3):322-424 .M Dental Implants/*; Human. .T Update on implants--techniques, technology explored. .P OVERALL. .I 275482 .U 91010259 .S J Am Dent Assoc 9101; 121(3):330, 332 .M Curriculum; Dental Implantation/*MA/TD; Education, Dental/*; Education, Dental, Continuing; Human. .T Education in implant dentistry. .P JOURNAL ARTICLE. .W Currently, relatively few dentists are qualified to practice implant dentistry; the demand for dental implants may soon exceed the profession's capacity to deliver this type of treatment. Accordingly, there is a salient need for national standards of education in the field. Implant education varies widely for practicing dentists, postdoctoral students, and predoctoral students. Although many schools are starting to teach implant dentistry in their predoctoral curricula, clinical and laboratory experience is limited. There are not enough trained professors, funding for new departments is limited, and change is often met with resistance. It is anticipated that within the decade, schools will establish departments, divisions, or sections dedicated to education in implant dentistry, despite these obstacles. .A Schnitman PA. .I 275483 .U 91010260 .S J Am Dent Assoc 9101; 121(3):334, 336, 338 .M Curriculum; Dental Implantation/*TD; Education, Dental/*; Faculty, Dental; Human; Specialties, Dental/*ED. .T Dental education--meeting the demands of implant dentistry. .P JOURNAL ARTICLE. .W Implant education is undergoing a transition from short, often superficial, continuing education to extended, hands-on experiences, based on clinical case studies. Dental schools previously ignored the need for in-depth implant education. Policy decisions related to future education are being considered in most dental undergraduate and postgraduate curricula. A broad-based implant education concept is proposed to meet the demands of a rapidly developing discipline. .A Misch CE. .I 275484 .U 91010261 .S J Am Dent Assoc 9101; 121(3):340-1, 344, 346 passim .M Comparative Study; Dental Implantation, Endosseous/*; Dental Implants/*; Denture Bases; Denture, Complete, Immediate; Denture, Overlay; Denture, Partial, Temporary; Dentures/*; Human; Osseointegration. .T Implant prosthodontics contribute to restorative dentistry [published erratum appears in J Am Dent Assoc 1990 Nov;121(5):582] .P JOURNAL ARTICLE. .W This paper is directed toward dental practitioners who accomplish the prosthodontic procedures for dental implants. It includes a discussion of most of the major steps in current implant dentistry. Several implant systems are compared with a look at the future of implant prosthodontics. .A Christensen GJ. .I 275485 .U 91010262 .S J Am Dent Assoc 9101; 121(3):352-3 .M Consumer Satisfaction; Dental Implants/*; Dentures/*; Esthetics, Dental; Goals; Human; Prosthodontics/*ST. .T Goals and limitations of implant prosthodontics. .P JOURNAL ARTICLE. .W Goal-driven treatment plans promote an accurate differential diagnosis resulting in appropriate implant prosthodontic treatment. The identification, understanding, and acceptance of the limitations of therapy assist both the doctor and the patient in achieving their objectives and minimizing disappointments. The implementation of such a regimen helps to achieve a successful result. .A Gilmer CE. .I 275486 .U 91010263 .S J Am Dent Assoc 9101; 121(3):355-8 .M Dental Abutments; Dental Implants/*; Dental Stress Analysis; Human; Osseointegration; Patient Care Planning; Problem Solving; Prosthesis Failure; Surgery, Oral, Preprosthetic; Tooth Extraction. .T Problem solving in implant dentistry. .P JOURNAL ARTICLE. .W Dental implants have become an accepted form of dental care, with reported functional 5-year success rates of 90% and higher. These impressive statistics include, but do not identify, the problems that may have been created by clinical ineptitude. Diagnostic acumen and preventive measures at each stage of the implant treatment can avoid many problems. Also, appropriate measures of timely recognition, rescue, and repair can often restore ailing implants and their prosthetic appliances to full function. .A Masters DH. .I 275487 .U 91010264 .S J Am Dent Assoc 9101; 121(3):360, 364, 366 passim .M Comparative Study; Dental Implantation, Endosseous/IS; Dental Implantation, Subperiosteal/IS; Dental Implants/*; Denture Design; Human. .T An overview of implant hardware [published erratum appears in J Am Dent Assoc 1990 Nov;121(5):582] .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W This paper overviews dental implants emphasizing design concepts, material composition, and prosthetic abutments. Within the space limitations, all systems can not be shown in total and we do not infer superiority or inferiority with the inclusion or exclusion of any design, concept, or abutment. .A English C. .I 275488 .U 91010265 .S J Am Dent Assoc 9101; 121(3):369, 372, 374 .M Bone Plates; Dental Implantation, Endosseous/*; Dental Implants/*; Dental Pins; Denture Design/*; Denture, Complete, Lower/*; Denture, Overlay; Human; Mandible/*SU. .T The fixed mandibular implant: its use in reconstructive prosthetics. .P JOURNAL ARTICLE. .W The main advantages of the FMI are immediate denture placement and function, the versatility for denture construction, and the absolutely parallel abutments that make prosthetic adaptation easy. During the submental approach, the oral and maxillofacial surgeon can perform cosmetic surgery of the submental fat pad and chin. There is usually less pain and swelling as compared with the intraoral dental procedure for placing four or five implants. The FMI is an excellent option for the anterior edentulous mandible or deformed mandible when fixed or fixed removable dentures or overdenture is needed. The team approach allows the surgeon and prosthetic dentist to combine their skills in the management of edentulous patients. .A Small IA. .I 275489 .U 91010266 .S J Am Dent Assoc 9101; 121(3):376, 378, 380 passim .M Dental Implantation, Endosseous/*MT; Dental Implants/*; Dental Pins; Denture, Complete, Immediate/*; Denture, Overlay; Human. .T Technique for screw-type implants. .P JOURNAL ARTICLE. .A Baumhammers A. .I 275490 .U 91010267 .S J Am Dent Assoc 9101; 121(3):384, 388, 390 passim .M Comparative Study; Dental Implantation, Endosseous/*MT; Dental Implants/*; Dental Pins; Denture Design; Human; Surgical Flaps. .T Implant systems incorporating the hollow-basket concept. .P JOURNAL ARTICLE. .W The hollow-basket design provides precise fit and stability after insertion, minimal bone destruction, and maximal bone-to-implant contact. Both systems, with careful attention to surgical protocol, will achieve osseointegration. .A Lubar RL; Katin RA. .I 275491 .U 91010268 .S J Am Dent Assoc 9101; 121(3):394, 396, 400 passim .M Blade Implantation/IS/*MT; Dental Abutments; Dental Implants/*; Dental Stress Analysis; Denture Design; Denture, Partial, Fixed; Human; Surgical Flaps. .T The blade implant. .P JOURNAL ARTICLE. .A Hahn JA. .I 275492 .U 91010269 .S J Am Dent Assoc 9101; 121(3):404-7 .M Alveolar Bone Loss/SU; Dental Implantation, Subperiosteal/*MT; Dental Implants/*; Denture Design; Denture, Complete, Upper/*; Denture, Overlay; Human; Maxilla/*SU; Maxillary Diseases/SU; Patient Care Planning. .T The restorative and surgical technique for the full maxillary subperiosteal implant. .P JOURNAL ARTICLE. .W The edentulous atrophic maxilla represents one of the most challenging implant restorative opportunities. When prescribed within the appropriate diagnostic range and performed by a highly skilled and experienced practitioner, the full maxillary subperiosteal implant is a predictable solution for the patient with an edentulous atrophic maxilla. .A Homoly PA. .I 275493 .U 91010270 .S J Am Dent Assoc 9101; 121(3):409-12 .M Dental Alloys; Dental Implantation, Endosseous/*MT; Dental Implants/*; Human; Hydroxyapatites; Pressure; Titanium. .T Technique for press-fit implants. .P JOURNAL ARTICLE. .W The press-fit implants can be used in any edentulous area with sufficient width and depth of bone for support. Clinical studies of at least one of the HA-coated systems have shown good results in the placement of the implant in extraction sockets, previous grafted ridges, and in conjunction with both autogeneous and synthetic bone grafts. The surgical placement must not traumatize the soft or hard tissue. The implant must be placed in a stressfree environment during the 3- or 4-month healing period. A variety of prosthetic components are available for both fixed and removable prostheses. .A Golec TS. .I 275494 .U 91010271 .S J Am Dent Assoc 9101; 121(3):414-7 .M Dental High-Speed Equipment; Dental Implantation, Endosseous/*MT; Dental Implants/*; Dental Impression Technique; Dental Pins; Human; Mandible/SU; Support, U.S. Gov't, Non-P.H.S.. .T Technique for placement of root form implants of the finned or serrated type. .P JOURNAL ARTICLE. .A Chess JT. .I 275495 .U 91010272 .S J Am Dent Assoc 9101; 121(3):418-20 .M Dental Implantation, Endosseous/*MT; Dental Implants/*; Denture Design/*; Denture, Complete, Lower; Human; Maxilla/SU. .T Ramus frame implant technique. .P JOURNAL ARTICLE. .A Turner HF. .I 275496 .U 91010273 .S J Am Dent Assoc 9101; 121(3):422-4 .M Anesthesia, Dental; Anesthesia, Local; Dental Implantation, Subperiosteal/*MT; Dental Implants/*; Dental Impression Technique; Dental Pins; Human; Mandible/SU; Surgical Flaps; Suture Techniques. .T A new technique for the subperiosteal implant. .P JOURNAL ARTICLE. .A Harris BW. .I 275497 .U 91010274 .S J Am Dent Assoc 9101; 121(3):436-7 .M Adult; Case Report; Dermatitis Medicamentosa/*ET; Erythema Multiforme/*CI; Human; Lip Diseases/PA; Male; Mouth Diseases/*CI; Mouth Mucosa/PA; Penicillins/*AE; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.. .T Multiple oral and skin lesions occurring after treatment with penicillin. .P JOURNAL ARTICLE. .W A case of erythema multiforme has been presented. Erythema multiforme may be a self-limiting or chronic disease, of varying severity. The disease is of significance to dental practitioners who may be called on to establish a diagnosis and provide appropriate referral or treatment, especially when lesions are limited to the mouth. The prognosis is generally good, although recurrence is common. .A Staretz LR; DeBoom GW. .I 275498 .U 91010275 .S J Am Dent Assoc 9101; 121(4):448 .M Air; Case Report; Child, Preschool; Dental High-Speed Equipment/*; Dental High-Speed Technique/*AE; Female; Human; Subcutaneous Emphysema/*ET. .T Facial emphysema after dental treatment [letter] .P LETTER. .A Austin GT; Pottorf B. .I 275499 .U 91010276 .S J Am Dent Assoc 9101; 121(4):449-50 .M Dental Devices, Home Care/*; Human; Toothbrushing/*. .T The debate continues ... [letter] .P LETTER. .I 275500 .U 91010277 .S J Am Dent Assoc 9101; 121(4):450, 452 .M Antibiotics/TU; Dental Care for Handicapped/*LJ; Dental Devices, Home Care/*; Endocarditis, Bacterial/ET; Human; Oral Hygiene/*AE; Premedication. .T Port polisher to debride the intraradicular area [letter] .P LETTER. .A Markus SJ. .I 275501 .U 91010278 .S J Am Dent Assoc 9101; 121(4):452 .M Dental Instruments/HI; History of Medicine, 20th Cent.; Periodontics/*HI; Wound Healing. .T The advent of surgical periodontal treatment [letter] .P HISTORICAL ARTICLE; LETTER. .A Markley MR. .I 275502 .U 91010279 .S J Am Dent Assoc 9101; 121(4):452, 454 .M Biopsy/*MT; Erythroplasia/DI; Human; Leukoplakia, Oral/*DI; Mouth Mucosa/*PA. .T Punch biopsy [letter; comment] .P COMMENT; LETTER. .A Abrams AM. .I 275503 .U 91010280 .S J Am Dent Assoc 9101; 121(4):454 .M Crowns/*; Human; Insurance, Dental; Nomenclature. .T Only diamonds are forever [letter] .P LETTER. .A Schmakel LP. .I 275504 .U 91010281 .S J Am Dent Assoc 9101; 121(4):460-4 .M Human; Periodontal Diseases/*DI/RA; Periodontics/IS. .T Diagnosing periodontal diseases. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W At present, the diagnosis of periodontal disease requires a clinical evaluation of the patient including visual findings, the use of the periodontal probe, and radiographs. No test is available to evaluate disease activity. In specific cases, adjunctive procedures may also be useful. The identification of pathogenic microorganisms may aid in evaluating the periodontal status of special patients. However, these are not required for an adequate diagnosis of the common adult form of chronic periodontitis. .A Barrington EP; Nevins M. .I 275505 .U 91010282 .S J Am Dent Assoc 9101; 121(4):467-70 .M Dental Plaque/TH; Dental Scaling; Human; Periodontal Diseases/DT/*TH; Subgingival Curettage. .T Reviewing nonsurgical periodontal therapy. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Selection of the appropriate case and clinical competency in treatment modalities results in success in nonsurgical periodontal therapy. The patient with early periodontitis with significant local factors in the form of professionally accessible plaque and calculus is the most receptive to nonsurgical periodontal treatment. The clinician must make decisions centering around the important question, "Can the patient, or moreover, can the therapist delivering the debridement, gain access to the microbial subgingival plaque on a frequent basis below the host defense threshold of the respective patient?" If the answer is "yes," nonsurgical periodontal therapy will be rewarding. If the answer is "no," other modalities such as periodontal surgery must be instituted. .A Low SB; Ciancio SG. .I 275506 .U 91010283 .S J Am Dent Assoc 9101; 121(4):473-6 .M Dental Restoration, Permanent; Gingivectomy; Human; Orthodontics, Corrective/*MT; Surgical Flaps; Tooth/*PA; Tooth Eruption/*. .T Lengthening clinical crowns. .P JOURNAL ARTICLE. .W Finding a solution to the short clinical crown is based on an appreciation of the biological width of attachment plus the dimensional requirements of sound restorative procedures. The collective talents of restorative dentist, orthodontist, and periodontist often are needed to cope with the problem. .A Johnson RH. .I 275507 .U 91010284 .S J Am Dent Assoc 9101; 121(4):479-81 .M Human; Periodontal Pocket/PA/*SU. .T Surgical pocket reduction. .P JOURNAL ARTICLE. .W It is not possible within the scope of this paper to describe in any detail each of the aforementioned procedures. These can be found in the various textbooks and journals on clinical periodontology. Instead, the objectives of treatment, the spectrum of techniques available, and the rationale for their use have been described. Periodontal surgery should be performed only under certain conditions: the patient must be physically and mentally competent to undergo any type of surgery, and should understand and agree to the procedure and to postoperative management. Finally, periodontal surgery should only be considered when nonsurgical therapy will not accomplish the desired result. When periodontal surgery for pocket elimination is performed for selected defects that have been properly evaluated after a debridement and healing period, and is executed with technical competence and proper postoperative care, it can preserve the dentition affected by periodontal disease. .A Kramer GM. .I 275508 .U 91010285 .S J Am Dent Assoc 9101; 121(4):485-8 .M Adolescence; Adult; Alveolar Ridge Augmentation/*; Female; Gingival Recession/*SU; Gingivoplasty/*MT; Human; Male; Middle Age; Mouth Mucosa/TR; Smoking/AE; Surgical Flaps; Tooth/*SU; Tooth Eruption. .T Using periodontal plastic surgery techniques. .P JOURNAL ARTICLE. .W In the 1980s, mucogingival surgery evolved into periodontal plastic surgery with various techniques designed to produce root coverage in areas of marginal tissue recession, to augment deficient ridges, and to lengthen crowns in cases of excessive gingival display. Periodontal plastic surgery not only enables the dentist to reconstruct but also to regenerate lost tissues. .A Miller PD Jr. .I 275509 .U 91010286 .S J Am Dent Assoc 9101; 121(4):491-4 .M After Care; Dental Prophylaxis; Human; Patient Compliance/*; Periodontal Diseases/*PC. .T Maintaining periodontal treatment. .P JOURNAL ARTICLE. .W Dental maintenance, or supportive periodontal treatment (SPT), can keep the periodontium and peri-implant tissues healthy after active therapy. Patients who comply to suggested SPT fare better periodontally and keep their teeth longer. Data should be gathered by examinations, talking with patients, and reviewing personal oral hygiene. Then sub- and supra-gingival deposits should be removed. The average SPT visit should last 1 hour and should be scheduled every 3 months. Supportive periodontal treatment for patients with more advanced periodontal or peri-implant destruction should be the responsibility of the periodontist. .A Wilson TG Jr. .I 275510 .U 91010287 .S J Am Dent Assoc 9101; 121(4):497-502 .M Alveolar Bone Loss/*SU; Biocompatible Materials; Bone Regeneration/*; Bone Transplantation/*; Calcium Phosphates; Ceramics; Composite Resins; Connective Tissue/PH; Epithelial Attachment/PH; Human; Hydroxyapatites; Implants, Artificial/*; Membranes, Artificial/*; Methylmethacrylates; Periodontal Diseases/*SU; Periodontal Ligament/PH; Polyhydroxyethyl Methacrylate. .T Regenerating bone in clinical periodontics. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Bone autografts and allografts, various alloplastic materials, and guided tissue regeneration are used to reconstruct lost periodontal tissues. This paper focuses on controversies related to these therapeutic modalities as well as their role in periodontal regeneration. .A Mellonig JT; Bowers GM. .I 275511 .U 91010288 .S J Am Dent Assoc 9101; 121(4):505-8 .M Case Report; Dental Implantation, Endosseous/*; Dental Implants/*; Female; Human; Periodontal Diseases/*SU; Tooth, Artificial/*. .T Dental implants used for periodontal patients. .P JOURNAL ARTICLE. .W For those performing implant treatment, continued research and reports of long-term successful results are essential to evaluating the validity of implants, especially when variables such as design and surface treatment are introduced. The dental profession has enthusiastically embraced the clinical results of implant treatment and its benefits to the patient. However, just as patients who undergo periodontal and restorative treatment must continue a regular long-term routine of maintenance therapy to ensure their dental health, so must those patients who receive dental implants. Both the periodontist who places the implants and the dentist who fabricates the prosthetic replacement must work cooperatively to deliver a healthy restoration that will function for many years. .A Langer B. .I 275512 .U 91010289 .S J Am Dent Assoc 9101; 121(4):511-3 .M Adult; Case Report; Human; Male; Molar/*IN; Patient Care Team; Post and Core Technique; Tooth Fractures/*SU; Tooth Movement, Minor/*; Tooth Root/IN. .T Premolarization of a fractured maxillary first molar: a multidisciplinary treatment. .P JOURNAL ARTICLE. .W The diagnosis and treatment of a fractured maxillary first molar are described in this case report of a 28-year-old male. Successful treatment of the retained palatal root of the fractured molar, referred to as premolarization, ensued from integration of endodontic, orthodontic, periodontic, and fixed prosthodontic care. .A De Franco DJ. .I 275513 .U 91010290 .S J Am Dent Assoc 9101; 121(4):515-7 .M Adult; Case Report; Female; Human; Malocclusion, Angle Class II/*CO; Patient Care Team; Periodontal Diseases/*CO; Post and Core Technique/*IS; Root Canal Therapy; Tooth Eruption; Tooth Movement, Minor/*MT. .T An esthetic approach to vertical root extrusion in a patient with an anterior open bite: report of case. .P JOURNAL ARTICLE. .W A previous attempt to locate the root canal system in the maxillary left central incisor with a bur created a perforating root defect at the level of the alveolar crest. The patient received root canal therapy. Next, vertical root extrusion was chosen to expose sound tooth structure apical to the defect so that a crown could be constructed. With an anterior open bite, the natural crown was left intact and it was possible to position the anchor bar in an incisal and lingual position, maintaining esthetics for the patient during both the extrusive and stabilization phases of treatment. .A Hartwell GR; McDonnell CJ 3d. .I 275514 .U 91010291 .S J Am Dent Assoc 9101; 121(4):519-23 .M Adolescence; Adult; Anesthesia, Dental/*AE/SN; Comparative Study; Dentists; Facial Injuries/EP; Female; Human; Lingual Nerve/*IN; Male; Middle Age; Nerve Block/*AE/SN; Questionnaires; Students, Dental. .T Incidence of lingual nerve trauma and postinjection complications in conventional mandibular block anesthesia. .P JOURNAL ARTICLE. .W Trauma to the lingual nerve is potential risk factor for patients receiving mandibular block anesthesia. This paper describes the results of a patient survey of 9,587 conventional mandibular blocks received by 2,289 adults. The incidence of lingual nerve trauma and postinjection complications is reported along with an associated analysis of the duration of complications, procedures at the time of incident, the side of occurrence (right or left), and gender ratios. In addition, recommendations for patient evaluation, treatment, and follow-up care are discussed. .A Harn SD; Durham TM. .I 275515 .U 91010292 .S J Am Dent Assoc 9101; 121(4):525-30 .M Adolescence; Adult; Aged; Anxiety/*TH; Behavior Therapy/*; Dental Care/*PX; Desensitization (Psychology); Female; Human; Indiana/EP; Kentucky/EP; Male; Middle Age; Ohio/EP; Phobic Disorders/TH; Program Evaluation; Questionnaires; Support, Non-U.S. Gov't; West Virginia/EP. .T Evaluating a behavioral method to manage dental fear: a 2-year study of dental practices. .P JOURNAL ARTICLE. .W Eleven private general practices and a university clinic formed a network to treat dental fear. The practices located in four states learned a method of treating dental fear using dental staff members and audiovisual materials. This study is an evaluation of the network's effectiveness. In 15 months, 111 patients were treated by the network. The dentists reported providing substantial dental treatment to 77% (n = 86) of the patients. The study showed that private general practices can effectively treat strong dental fear. .A Smith TA; Kroeger RF; Lyon HE; Mullins MR. .I 275516 .U 91010293 .S J Am Dent Assoc 9101; 121(4):532-6 .M Adolescence; Adult; Arizona/EP; Child; Child, Preschool; Cross-Sectional Studies; Diabetes Mellitus, Non-Insulin-Dependent/*CO/EP; Female; Human; Indians, North American/*; Male; Middle Age; Periodontal Diseases/*CO/EP; Support, U.S. Gov't, P.H.S.. .T Type 2 diabetes mellitus and periodontal disease. .P JOURNAL ARTICLE. .W The relationship between type 2 diabetes mellitus and periodontal disease was evaluated in 2,878 Pima Indians of the southwestern United States. Two independent measures of periodontal disease, probing attachment loss and radiographic bone loss, were used to compare prevalence and severity of periodontal disease in diabetic and nondiabetic subjects. In all age groups studied, subjects with diabetes had a higher prevalence of periodontal disease, indicating that diabetes may be a risk factor for periodontal disease. .A Shlossman M; Knowler WC; Pettitt DJ; Genco RJ. .I 275517 .U 91010294 .S J Am Dent Assoc 9101; 121(4):537-8 .M American Dental Association; Dental Care for Handicapped/*; Human; Joint Prosthesis/*; Premedication; Septicemia/PC; United States. .T Management of dental patients with prosthetic joints. Council on Dental Therapeutics. .P MEETING REPORT. .I 275518 .U 91010295 .S J Am Dent Assoc 9101; 121(4):541-3 .M Anti-Infective Agents, Local/TU; Dental Devices, Home Care; Dental Plaque/PC; Dental Prophylaxis/*; Human; Irrigation; Periodontitis/*DT; Tooth Root/PA. .T Periodontal therapy: reviewing subgingival irrigations and future considerations. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .A Goodman CH; Robinson PJ. .I 275519 .U 91010296 .S J Am Dent Assoc 9101; 121(4):559-60 .M Case Report; Fibroma/*PA; Gingival Neoplasms/*PA; Human; Male; Middle Age; Osteoma/*PA; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.. .T Proliferative mass found in the gingiva. .P JOURNAL ARTICLE. .W The clinical course of peripheral ossifying fibroma is slow and the growth of most lesions is limited in size, usually up to 1.5 cm. Complaints are rare unless the surface becomes ulcerated, or the lesion compromises oral function or esthetic appearance. Treatment is surgical excision with close postoperative follow-up. Tooth extraction is seldom necessary. Proper surgical intervention, which includes excision of reactive tissue down to periosteum, affords a low recurrence rate of 14% to 16%. .A Miller CS; Henry RG; Damm DD. .I 275520 .U 91010297 .S J Am Coll Cardiol 9101; 16(4):1000-9 .M Cerebral Embolism and Thrombosis/*ET; Echocardiography/*MT; Female; Heart Aneurysm/CO/EP/*US; Heart Diseases/US; Heart Septum; Human; Male; Middle Age; Retrospective Studies; Thrombosis/US. .T Improved morphologic characterization of atrial septal aneurysm by transesophageal echocardiography: relation to cerebrovascular events. .P JOURNAL ARTICLE. .W Transthoracic and transesophageal echocardiography was performed in 23 consecutive adult patients with an atrial septal aneurysm. In three patients with a cerebrovascular event the diagnosis was established by the transesophageal approach only. Interatrial shunting on transthoracic imaging with use of echocardiographic contrast imaging or Doppler color mapping, or both, was detected in 7 (41%) of 17 patients. On performing contrast imaging in combination with color flow mapping during transesophageal echocardiography, positive shunting was demonstrated in 15 (83%) of 18 patients. Echocardiographic identification of multiple fenestrations (n = 4) and thrombus within the aneurysm (n = 2) could be achieved for the first time by transesophageal ultrasound application. Cerebrovascular events occurred in 12 (52%) of 23 patients and were regarded as being definitely thromboembolic in 10 (43%); 8 (67%) of the 12 patients had repeated cerebral events. Except for mitral valve prolapse in one patient, no other potential cardiac source of embolism could be identified despite the use of transesophageal echocardiography. A thickening of the aneurysmal membrane greater than or equal to 5 mm was found in 9 (75%) of 12 patients with versus 3 (27%) of 11 patients without a cerebrovascular event (p less than 0.05); this proved to be the only significant difference between the two patient groups. The mechanism of embolization may be both primary thrombus formation within the aneurysm and paradoxic embolization through an interatrial communication as demonstrated by the findings in two patients. It is concluded that atrial septal aneurysm is a cardiac abnormality with thromboembolic potential. In patients with this lesion and a history of an embolic event, long-term anticoagulant therapy is indicated. .A Schneider B; Hanrath P; Vogel P; Meinertz T. .I 275521 .U 91010298 .S J Am Coll Cardiol 9101; 16(4):1010-6 .M Adult; Blood Flow Velocity/PH; Coronary Circulation/PH; Echocardiography, Doppler/*MT; Female; Heart Septal Defects, Atrial/*US; Human; Male. .T Transesophageal Doppler color flow mapping assessment of atrial septal defect. .P JOURNAL ARTICLE. .W Transesophageal Doppler color flow imaging was performed in 19 adult patients (mean age 35 years) with an atrial septal defect demonstrated by cardiac catheterization or at surgery, or both. The transesophageal study correctly identified and classified 19 of 19 shunts in contrast to 16 of 18 shunts identified by the transthoracic approach. The area of the atrial septal defect was calculated by assuming it to be circular and taking the maximal Doppler color flow jet width at the defect site as its diameter. The pulsed Doppler sample volume was placed parallel to the shunt flow direction at the defect site to obtain the mean velocity and flow duration. From these values, the shunt volume was calculated as a product of the defect area, mean velocity, flow duration and heart rate. The calculated shunt flow volume obtained by transesophageal study showed a good correlation with shunt flow volume (r = 0.91, p less than 0.001) and pulmonary to systemic blood flow ratio (r = 0.84, p less than 0.001) obtained at cardiac catheterization. The size of the defect by transesophageal Doppler color flow mapping correlated fairly well with the size estimated at surgery (r = 0.73, p = 0.004). It is concluded that transesophageal Doppler color flow imaging is useful in the detection and classification of atrial septal defects and in the assessment of shunt volumes. .A Mehta RH; Helmcke F; Nanda NC; Hsiung M; Pacifico AD; Hsu TL. .I 275522 .U 91010299 .S J Am Coll Cardiol 9101; 16(4):1017-21 .M Bayes Theorem; Bias (Epidemiology); Coronary Disease/EP/*RI; Human; Predictive Value of Tests; Sensitivity and Specificity; Support, U.S. Gov't, P.H.S.; Thallium Radioisotopes/*DU; Tomography, Emission-Computed, Single-Photon/*. .T How accurate is SPECT thallium scintigraphy? [editorial] [see comments] .P EDITORIAL. .A Diamond GA. .I 275523 .U 91010300 .S J Am Coll Cardiol 9101; 16(4):1022-3 .M Bias (Epidemiology); Coronary Disease/EP/*RI; Exercise Test; Human; Sensitivity and Specificity; Thallium Radioisotopes/*DU; Tomography, Emission-Computed, Single-Photon/*. .T Agreement on the accuracy of thallium stress testing [editorial; comment] .P COMMENT; EDITORIAL. .A Gould KL. .I 275524 .U 91010301 .S J Am Coll Cardiol 9101; 16(4):1024-5 .M Bayes Theorem; Bias (Epidemiology); Coronary Disease/*RI; Exercise Test; False Negative Reactions; False Positive Reactions; Human; Sensitivity and Specificity; Thallium Radioisotopes/*DU; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon/*. .T SPECT thallium imaging in the diagnosis of myocardial ischemia [editorial; comment] .P COMMENT; EDITORIAL. .A Iskandrian AS. .I 275525 .U 91010302 .S J Am Coll Cardiol 9101; 16(4):1026-8 .M Acute Disease; Chest Pain/DI; Coronary Disease/*DI; Coronary Thrombosis/*DI; Electrocardiography/*; Human. .T The electrocardiogram in the acute coronary syndromes [editorial] [comment] .P COMMENT; EDITORIAL. .A Ayres SM. .I 275526 .U 91010304 .S J Am Coll Cardiol 9101; 16(4):1032-56 .M Cardiology/*ED; Education; Heart Surgery/*ED; Thoracic Surgery/*ED; United States. .T Training programs in the United States in adult cardiology, pediatric cardiology and cardiothoracic surgery. .P JOURNAL ARTICLE. .I 275527 .U 91010305 .S J Am Coll Cardiol 9101; 16(4):1057-9 .M Cardiology/*/ST; Cardiovascular Diseases/*; Clinical Protocols; Health Services Needs and Demand/*; Human; Societies, Medical/*; United States. .T ACC testimony on the increased demand for cardiovascular services [news] .P NEWS. .A Winters WL Jr. .I 275528 .U 91010306 .S J Am Coll Cardiol 9101; 16(4):763-9 .M Cognition; Coronary Arteriosclerosis/RA; Coronary Circulation/*PH; Coronary Disease/DI/*RA; Coronary Vessels/*RA; Heart/*RI; Human. .T Cognition in the era of technology: "seeing the shades of gray". .P JOURNAL ARTICLE. .A Klocke FJ. .I 275529 .U 91010309 .S J Am Coll Cardiol 9101; 16(4):784-92 .M Age Factors; Aged; Aged, 80 and over; Angina Pectoris/EP; Comparative Study; Female; Follow-Up Studies; Heart Failure, Congestive/EP; Human; Male; Multivariate Analysis; Myocardial Infarction/*MO; Prognosis; Sex Factors; Smoking/EP; Support, U.S. Gov't, P.H.S.; Survival Analysis; Time Factors. .T Outlook after acute myocardial infarction in the very elderly compared with that in patients aged 65 to 75 years [see comments] .P JOURNAL ARTICLE. .W Little is known concerning late outcome and prognostic factors after acute myocardial infarction in the very elderly (greater than 75 years of age). Accordingly, this study compared the clinical course and mortality rate for up to 1 year in a large multicenter data base that included 702 patients greater than 75 years of age (mean +/- SD 81 +/- 4 years), with a less elderly subset of 1,321 patients between 65 and 75 years of age (mean 70 +/- 3 years). The postdischarge 1 year cardiac mortality rate was 17.6% for those greater than 75 years of age compared with 12.0% for patients between 65 and 75 years of age (p less than 0.01). There were differences in the prevalence of several factors, including female gender, history of angina pectoris, history of congestive heart failure, smoking habits and incidence of congestive heart failure during hospitalization. Multivariate analyses of predictors of cardiac death in hospital survivors selected different factors as important in the two age subgroups; age was selected in the 65 to 75 year age group but was not an independent predictor in the very elderly. The survival curves beginning at day 10 for patients 65 to 75 and in those greater than 75 years old were similar for up to 90 days but diverged later. In the very elderly, 63% of late cardiac deaths were sudden or due to new myocardial infarction, similar to the causes of 67% of deaths in the younger age group.(ABSTRACT TRUNCATED AT 250 WORDS) .A Smith SC Jr; Gilpin E; Ahnve S; Dittrich H; Nicod P; Henning H; Ross J Jr. .I 275530 .U 91010310 .S J Am Coll Cardiol 9101; 16(4):793-4 .M Aged; Aged, 80 and over; Bias (Epidemiology); Human; Myocardial Infarction/*MO; Physician's Practice Patterns; Prognosis; Referral and Consultation. .T The elderly, the very elderly and traditional practice patterns [editorial; comment] .P COMMENT; EDITORIAL. .A Adolph RJ. .I 275531 .U 91010311 .S J Am Coll Cardiol 9101; 16(4):795-803 .M Aged; Aortic Valve Stenosis/PP/*TH; Balloon Dilatation/*; Comparative Study; Diastole/*PH; Echocardiography; Female; Follow-Up Studies; Gated Blood-Pool Imaging; Heart/RI; Heart Catheterization; Human; Male; Support, U.S. Gov't, P.H.S.; Time Factors; Ventricular Function, Left/*PH. .T Changes in left ventricular diastolic performance after aortic balloon valvuloplasty: acute and late effects [see comments] .P JOURNAL ARTICLE. .W To evaluate acute and follow-up changes in left ventricular diastolic performance, simultaneous digital left ventriculography and micromanometry were performed in 49 patients undergoing aortic balloon valvuloplasty. All patients improved symptomatically after valvuloplasty, and 26 returned 6.3 +/- 1.5 months later for follow-up catheterization. Immediately after valvuloplasty, aortic valve area increased (before 0.5 +/- 0.2 versus after 0.8 +/- 0.2 cm2, p less than 0.01), cardiac output (before 4.3 +/- 1.2 versus after 4.4 +/- 1.3 liters/min) and ejection fraction (before 51 +/- 18% versus after 52 +/- 17%) did not change and diastolic indexes worsened, signified by a decrease in peak filling rate (before 247 +/- 80 versus after 226 +/- 78 ml/s, p less than 0.01) and increase in the time constant of isovolumetric relaxation (tau) (before 78 +/- 29 versus after 96 +/- 40 ms, p less than 0.01) and the modulus of chamber stiffness (before 0.107 +/- 0.071 versus after 0.141 +/- 0.083, p less than 0.01). At follow-up catheterization, 16 patients continued to have symptomatic improvement (group 1) and 10 had recurrence of symptoms (group 2). Aortic valve area, cardiac output and ejection fraction at follow-up catheterization in both groups were similar and unchanged from values before valvuloplasty.(ABSTRACT TRUNCATED AT 250 WORDS) .A Sheikh KH; Davidson CJ; Honan MB; Skelton TN; Kisslo KB; Bashore TM. .I 275532 .U 91010312 .S J Am Coll Cardiol 9101; 16(4):804-6 .M Aortic Valve Stenosis/PP/*TH; Balloon Dilatation/*; Diastole/*PH; Human; Ventricular Function, Left/*PH. .T Percutaneous aortic balloon valvuloplasty: relief of obstruction to outflow or inflow? [editorial; comment] .P COMMENT; EDITORIAL. .A Nishimura RA; Reeder GS. .I 275533 .U 91010313 .S J Am Coll Cardiol 9101; 16(4):807-11 .M Angina, Unstable/MO/*TH; Angioplasty, Transluminal, Percutaneous Coronary/*; Coronary Artery Bypass/CT; Female; Human; Male; Middle Age; Myocardial Infarction/MO/*TH; Retrospective Studies; Risk Factors; Stroke Volume/PH; Survival Analysis; Ventricular Function, Left/*PH. .T Coronary angioplasty in patients with severe left ventricular dysfunction. .P JOURNAL ARTICLE. .W The applications for coronary angioplasty have greatly expanded and the procedure is now increasingly used in complex and potentially high risk conditions. This report describes the short- and long-term effects of coronary angioplasty in 61 patients with severely depressed left ventricular function (ejection fraction less than or equal to 35%) with unstable or refractory anginal symptoms, or both, in whom revascularization was necessary despite increased risk. In a retrospective analysis of 1,260 patients undergoing angioplasty between January 1985 through December 1987, 61 had an ejection fraction less than or equal to 35%. The common clinical presentation was unstable angina (70%) with or without recent myocardial infarction. Mean left ventricular ejection fraction was 27 +/- 6%. Forty-five patients (74%) had multivessel disease. Clinical success after angioplasty was achieved in 55 patients (90%). Major complications (death, infarction and emergency bypass surgery) occurred in five patients (8.2%), with death in two (3.2%). During long-term (mean 21 +/- 11 months) follow-up study of the 55 patients with successful angioplasty, 13 (23%) died, including 3 of noncardiac causes, and 11 (20%) had clinically symptomatic recurrence. Continued clinical success was present in 39 patients (71%), of whom 28 (51%) were event-free patients and 11 (20%) had clinical recurrence; a successful second angioplasty procedure was performed in 9 because of restenosis. Thus, in patients with depressed left ventricular function, coronary angioplasty can be performed with a short-term success rate comparable to that of routine angioplasty or surgical procedures. However, acute complications are more frequent and the late mortality rate is higher than in patients with less depressed function. .A Kohli RS; DiSciascio G; Cowley MJ; Nath A; Goudreau E; Vetrovec GW. .I 275534 .U 91010314 .S J Am Coll Cardiol 9101; 16(4):812-20 .M Angina Pectoris/MO/*TH; Angioplasty, Transluminal, Percutaneous Coronary/*MO; Cohort Studies; Coronary Artery Bypass/*; Female; Follow-Up Studies; Graft Occlusion, Vascular/TH; Human; Male; Middle Age; Myocardial Infarction/MO; Reoperation; Survival Analysis; Time Factors. .T Coronary angioplasty after coronary bypass surgery: initial results and late outcome in 422 patients. .P JOURNAL ARTICLE. .W From 1978 to 1988, coronary angioplasty was performed in 422 patients with prior coronary artery bypass surgery (264 patients with native coronary artery angioplasty and 158 patients with graft angioplasty). Angioplasty was successful in 84%, unsuccessful but uncomplicated in 11% and complicated by one or more major cardiac events in 5% (myocardial infarction 5%, emergency bypass surgery 2% and death 0.2%). Follow-up data were obtained in 99% of 356 patients with successful angioplasty. At a mean of 33 +/- 26 months, 92% were alive, 73% had improvement in angina and 61% were free of angina. One or more of the following late events occurred in 67 patients (19%): myocardial infarction (6%), elective reoperation (13%) and cardiac death (6%). Repeat angioplasty was performed in 27%, with a success rate of 89% and no deaths. Initial success rates were equal in native vessel versus graft angioplasty, but late outcome was less favorable with the latter because of a higher rate of infarction (11% versus 4%, p less than 0.05) and need for reoperation (19% versus 10%, p less than 0.05). The initial success rate was higher in vein grafts less than 1 year old compared with grafts 1 to 4 years or greater than 4 years after operation (92% versus 85% versus 83%, respectively) and adverse late events were less frequent after angioplasty in recent vein grafts (less than 1 year 13%, 1 to 4 years 35%, greater than 4 years 29%; less than 1 versus greater than 1 year, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) .A Webb JG; Myler RK; Shaw RE; Anwar A; Mayo JR; Murphy MC; Cumberland DC; Stertzer SH. .I 275535 .U 91010315 .S J Am Coll Cardiol 9101; 16(4):821-6 .M Aged; Cardiomyopathy, Hypertrophic/*MO/US; Comparative Study; Echocardiography; Female; Follow-Up Studies; Human; Male; Prognosis; Survival Analysis; Survival Rate; Time Factors. .T Natural history of hypertrophic cardiomyopathy in the elderly. .P JOURNAL ARTICLE. .W The prognosis of patients diagnosed as having hypertrophic cardiomyopathy at advanced age has not been well defined. This study details follow-up information obtained for 95 patients initially diagnosed as having hypertrophic cardiomyopathy at age greater than or equal to 65 years. Seventy-five percent of patients were symptomatic, as defined by the presence of chest pain, dyspnea or syncope, and the mean ventricular septal thickness was 20 mm. The median duration of follow-up study was 4.2 years. The survival rate at 1 and 5 years was 95% and 76%, respectively, which was not significantly different from that an age- and gender-matched control group. Of patients presenting with New York Heart Association functional class I or II dyspnea, only 18% progressed to class III or IV during the follow-up period. However, patients presenting with class III dyspnea had a 1 year mortality rate of 36%, significantly higher than that of control subjects (p less than 0.003). Of the echocardiographic variables, indexed left atrial size was most strongly associated with reduced survival (p less than 0.008). These results suggest that the prognosis of elderly patients with hypertrophic cardiomyopathy is generally favorable. Certain clinical and echocardiographic variables appear to be of use in identifying patients with a less favorable prognosis. .A Fay WP; Taliercio CP; Ilstrup DM; Tajik AJ; Gersh BJ. .I 275536 .U 91010316 .S J Am Coll Cardiol 9101; 16(4):827-31 .M Comparative Study; Female; Follow-Up Studies; Heart Failure, Congestive/*BL/MO; Human; Magnesium/*BL; Male; Middle Age; Prevalence; Prognosis; Support, U.S. Gov't, P.H.S.; Survival Analysis; Survival Rate; Time Factors. .T Prognostic importance of the serum magnesium concentration in patients with congestive heart failure. .P JOURNAL ARTICLE. .W Magnesium abnormalities are common in patients with congestive heart failure but the clinical and prognostic significance of an abnormal serum magnesium concentration in this disorder has not been investigated. Therefore, the relation between serum magnesium concentration and the clinical characteristics and long-term outcome of 199 patients with chronic heart failure was evaluated. The serum magnesium concentration was less than 1.6 mEq/liter in 38 patients (19%), within the normal range in 134 patients (67%) and greater than 2.1 mEq/liter in 27 patients (14%). Patients with hypomagnesemia had more frequent ventricular premature complexes and episodes of ventricular tachycardia than did patients with a normal serum magnesium concentration (p less than 0.05). Even though the two groups were similar with respect to severity of heart failure and neurohormonal variables, patients with a low serum magnesium concentration had a significantly worse prognosis during long-term follow-up (45% versus 71% 1 year survival, p less than 0.05). Patients with hypermagnesemia had more severe symptoms, greater neurohormonal activation and worse renal function than did patients with a normal serum magnesium concentration but tended to have fewer ventricular arrhythmias. Hypermagnesemic patients had a worse prognosis than did those with a normal magnesium concentration (37% versus 71% 1 year survival, p less than 0.05). In conclusion, the measurement of serum magnesium concentration provides important clinical and prognostic information in patients with chronic heart failure. .A Gottlieb SS; Baruch L; Kukin ML; Bernstein JL; Fisher ML; Packer M. .I 275537 .U 91010317 .S J Am Coll Cardiol 9101; 16(4):832-7 .M Arrhythmia, Sinus/*EP/ET; Bradycardia/*EP/ET; Cardiac Pacing, Artificial; Electrocardiography; Female; Follow-Up Studies; Heart Transplantation/*; Human; Incidence; Male; Middle Age; Monitoring, Physiologic; Pacemaker, Artificial; Tachycardia, Supraventricular/*EP/ET; Telemetry; Time Factors. .T Cardiac rhythm disturbances early after orthotopic heart transplantation: prevalence and clinical importance of the observed abnormalities. .P JOURNAL ARTICLE. .W To precisely define the incidence, type and consequences of cardiac arrhythmias early after heart transplantation, 25 cardiac transplant recipients were monitored continuously for 728 days from the day of surgery to discharge or death. A subset of 15 patients had sinus node function studies with overdrive suppression performed weekly at the time of endomyocardial biopsy. Results revealed sinus bradycardia in 10 patients (40%) and junctional bradycardia in 6 (24%). Supraventricular tachycardia in the form of atrial tachycardia, atrial fibrillation and atrial flutter occurred in 11 patients (44%). Ventricular tachycardia occurred in 15 patients (60%) and was nonsustained in all. Cardiac pacing for 1,403 h was used in nine patients with a pulse rate less than 50 beats/min; seven recovered and permanent pacing was instituted in two. In the subgroup that had sinus node function studies, seven patients were identified with clinical bradyarrhythmia; each had abnormal sinus node recovery time (greater than 1,400 ms) and abnormal corrected sinus node recovery time (greater than 525 ms) in at least one study. These seven patients also had a significantly prolonged ischemic time (236 +/- 26 versus 159 +/- 68 min, p less than 0.01). In conclusion, cardiac arrhythmias, particularly ventricular tachycardia and bradyarrhythmia, occur more commonly early after orthotopic heart transplantation than has previously been reported. Sinus node dysfunction due to prolonged organ ischemic time, antiarrhythmic drug use or surgical trauma, alone or in combination, may contribute to these arrhythmias. .A Jacquet L; Ziady G; Stein K; Griffith B; Armitage J; Hardesty R; Kormos R. .I 275538 .U 91010319 .S J Am Coll Cardiol 9101; 16(4):847-54 .M Activities of Daily Living/*; Adult; Cold/DU; Comparative Study; Exercise Test; Female; Heart/*RI; Human; Male; Mental Processes/PH; Monitoring, Physiologic/*IS; Radionuclide Ventriculography/*IS; Stroke Volume/*PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Comparison of physiologic ejection fraction responses to activities of daily living: implications for clinical testing. .P JOURNAL ARTICLE. .W The recent development of the VEST, an ambulatory radionuclide detector, to measure left ventricular ejection fraction may enhance the detection of ischemia during daily activities in patients with coronary artery disease. The normal range and determinants of ejection fraction responses to stimuli other than physical exercise, however, are not adequately characterized. Therefore, ejection fraction responses to various activities were measured in 18 normal subjects utilizing the VEST. Uniform increases (greater than 5%) in ejection fraction were seen during physical exercise, uniform decreases were seen during cold pressor testing and modest changes (including decreases greater than 5%) were seen in ejection fraction during mental stress, micturition and hyperventilation. Different forms of stress produced significantly different changes in ejection fraction, even when values were controlled for changes in heart rate. Ventricular loading conditions in the form of enhanced blood pressure responses during mental stress may have contributed to the relatively smaller changes in ejection fraction compared with those during exercise. Subjects demonstrating a decrease in ejection fraction during mental stress did not differ from other subjects in hemodynamic reactivity during mental testing but did have evidence of increased parasympathetic tone during cold pressor and bicycle exercise testing. The results reveal that normal ejection fraction response differs among varying physiologic stimuli. These changes are in part related to changes in heart rate and blood pressure; however, other factors, such as neurohumoral regulation, may also play a role. These findings indicate that the patient's activity and the setting in which it occurs must be considered when interpreting ambulatory ejection fraction responses. .A Bairey CN; de Yang L; Berman DS; Rozanski A. .I 275539 .U 91010323 .S J Am Coll Cardiol 9101; 16(4):878-86 .M Action Potentials/PH; Animal; Cardiac Pacing, Artificial/*; Dogs; Electrocardiography; Electrodes; Equipment Design; Female; Heart/*PH; Heart Catheterization/*IS; Human; Male; Pacemaker, Artificial/*; Refractory Period, Neurologic/PH; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tachycardia, Supraventricular/DI; Time Factors. .T A new single catheter technique for simultaneous measurement of action potential duration and refractory period in vivo. .P JOURNAL ARTICLE. .W In vivo correlations of action potential duration measured by a monophasic action potential catheter and effective refractory period measured by a separate pacing catheter have been poor, probably because of the known variability of both action potential duration and effective refractory period between different ventricular sites. In this study, a new quadripolar contact electrode catheter designed for simultaneous pacing and monophasic action potential recording at closely adjacent sites (2 mm separation between recording electrodes and pacing electrodes) was tested in five closed chest dogs and four patients. Dog studies: Pacing thresholds were extremely low, ranging from 0.02 to 0.25 mA (mean +/- SD 0.099 +/- 0.051, n = 36) and were stable over time (less than 20% increase during 1 h of continuous pacing). Because of the close proximity of pacing and recording electrodes, the pacing artifact nearly coincided with the monophasic action potential upstroke. Because of the low pacing threshold, however, pacing artifacts were small (33 +/- 17% of the monophasic action potential amplitude at twice diastolic threshold strength) and did not affect the duration or configuration of the simultaneously recorded monophasic action potential. The short stimulus response time and the undisturbed monophasic action potential signal fidelity during pacing allowed precise simultaneous measurements of action potential duration and effective refractory period at the same endocardial site.(ABSTRACT TRUNCATED AT 250 WORDS) .A Franz MR; Chin MC; Sharkey HR; Griffin JC; Scheinman MM. .I 275540 .U 91010324 .S J Am Coll Cardiol 9101; 16(4):887-95 .M Aged; Comparative Study; Coronary Vessels/*; Electric Countershock/IS/*MT; Electrodes; Electrodes, Implanted; Equipment Design; Female; Heart Catheterization/IS; Human; Male; Middle Age; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Ventricular Fibrillation/PC. .T An effective and adaptable transvenous defibrillation system using the coronary sinus in humans. .P JOURNAL ARTICLE. .W With use of a coronary sinus catheter electrode, a right ventricular catheter electrode and a chest wall patch electrode system, defibrillation threshold voltage, current and energy were measured with four distinct transvenous defibrillation techniques delivered in random sequence in each of 12 survivors of cardiac arrest immediately before implantation of a standard epicardial patch defibrillation system. The four transvenous defibrillation techniques were 1) single pathway monophasic pulsing, 2) single pathway biphasic pulsing, 3) dual pathway sequential pulsing, and 4) dual pathway simultaneous pulsing. A transvenous defibrillation method was considered to be potentially useful only if the defibrillation threshold was less than or equal to 500 V (less than or equal to 15 J delivered energy). The 500 V value would allow a 2:1 defibrillation safety margin for a device with a maximal output of 30 J. No single transvenous pulsing technique was uniformly superior in efficacy. However, by choosing the best pulsing technique for each patient, it was possible to obtain an average defibrillation threshold of 410 +/- 135 V leading edge voltage, 7.2 +/- 2.5 A leading edge current and 11.3 +/- 7.4 J delivered energy for the group of 12 patients. With the ability to vary defibrillation technique, transvenous antiarrhythmic device implantation would have been possible in 10 (83%) of the 12 patients at or below a 15 J defibrillation threshold cutoff point. In contrast, if only one transvenous defibrillation method had been used, as few as 5 and at most 8 of the 12 patients would have been candidates for a transvenous defibrillation system given a 15 J defibrillation threshold cutoff point for insertion.(ABSTRACT TRUNCATED AT 250 WORDS) .A Bardy GH; Allen MD; Mehra R; Johnson G. .I 275541 .U 91010325 .S J Am Coll Cardiol 9101; 16(4):896-902 .M Adolescence; Cardiomyopathy, Congestive/TH; Cardiomyopathy, Hypertrophic/TH; Death, Sudden/EP; Electric Countershock/*IS; Female; Follow-Up Studies; Heart Defects, Congenital/TH; Human; Life Style; Life Tables; Male; Survival Rate; Tachycardia/MO/*PC; Time Factors. .T The automatic implantable cardioverter-defibrillator in young patients. .P JOURNAL ARTICLE. .W An international survey identified 40 patients less than 20 years old who underwent surgical implantation of an automatic implantable cardioverter-defibrillator (AICD). There was a history of aborted sudden cardiac death or sustained ventricular tachycardia in 92.5% of these patients. Twenty-two patients (55%) had structural heart disease; dilated and hypertrophic cardiomyopathy were the most common diagnoses. Eighteen patients (45%) had primary electrical abnormalities including seven with the congenital long QT syndrome. There were no perioperative deaths associated with device implantation. Concomitant drug therapy was administered to 75% of the patients. Defibrillator discharge occurred in 70% of the patients, with 17 patients (42.5%) receiving at least one appropriate shock. There were two sudden and two nonsudden deaths at 28.2 months' median follow-up. Sudden death-free survival rates by life table analysis at 12 and 33 months were 0.94 and 0.88, respectively. Total survival rates at 12 and 33 months were 0.94 and 0.82, respectively. The AICD represents an effective treatment approach for young patients with life-threatening ventricular tachyarrhythmias. .A Kron J; Oliver RP; Norsted S; Silka MJ. .I 275542 .U 91010326 .S J Am Coll Cardiol 9101; 16(4):903-12 .M Child, Preschool; Echocardiography, Doppler/*; Heart Catheterization; Heart Defects, Congenital/SU/*US; Heart Septal Defects/US; Heart Valve Diseases/US; Human; Postoperative Care; Prospective Studies; Support, Non-U.S. Gov't; Ventricular Outflow Obstruction/US. .T Accuracy of prospective two-dimensional/Doppler echocardiography in the assessment of reparative surgery. .P JOURNAL ARTICLE. .W Between January 1987 and January 1989, all 129 patients (aged 11 days to 25 years, median 39 months) undergoing both an echocardiographic examination and cardiac catheterization after reparative surgery were prospectively included in a study to assess the accuracy of combined two-dimensional and Doppler color flow imaging. The patient diagnoses were transposition of the great arteries (n = 20), tetralogy of Fallot (n = 38), coarctation of the aorta (n = 24), complete atrioventricular (AV) canal (n = 15), atrial septal defect (n = 8), ventricular septal defects (n = 3), pulmonary stenosis (n = 4), aortic stenosis (n = 8) and subaortic stenosis (n = 9). In arterial tract stenosis, there was high correlation between Doppler estimates and catheterization-derived measurements of residual right ventricular outflow tract obstruction in patients after the arterial switch operation for transposition of the great arteries (r = 0.95) as well as in patients after corrective repair of tetralogy of Fallot (r = 0.84). In semilunar/AV valve regurgitation, graded as none, mild, moderate or severe, echocardiographic estimates correlated exactly with angiographic grading in 84% and differed by one angiographic grade in the other 16%. In residual left to right shunting, no hemodynamically significant shunt was missed by echocardiography. For residual shunts at the ventricular level (n = 32), addition of Doppler color flow imaging improved the sensitivity (from 63% to 94%) and the negative predictive value (from 88% to 98%). In elevated right ventricular pressure, Doppler-derived right ventricular-right atrial pressure estimates in 24 patients correlated well with catheterization measurements (r = 0.93). Combined two-dimensional and Doppler color flow echocardiography was highly accurate in the prospective evaluation of these four types of postoperative residual. .A Chang AC; Vetter JM; Gill SE; Franklin WH; Murphy JD; Chin AJ. .I 275543 .U 91010327 .S J Am Coll Cardiol 9101; 16(4):913-20 .M Child; Comparative Study; Echocardiography, Doppler/*MT; Heart Defects, Congenital/SU/*US; Heart Septal Defects/US; Human; Intraoperative Care/MT; Postoperative Care/MT; Reoperation; Support, Non-U.S. Gov't; Tricuspid Valve Insufficiency/US; Ventricular Outflow Obstruction/US. .T Comparative roles of intraoperative epicardial and early postoperative transthoracic echocardiography in the assessment of surgical repair of congenital heart defects [see comments] .P JOURNAL ARTICLE. .W In 94 consecutive patients undergoing surgical repair of congenital heart defects the results of intraoperative (after cardiopulmonary bypass) epicardial two-dimensional and Doppler color flow imaging were compared with those of sequential transthoracic echocardiography performed within 24 h of surgery and again before hospital discharge to define the precise role of intraoperative imaging. In 6 of 7 patients with a residual defect requiring immediate surgical revision, intraoperative imaging correctly identified the defect; spectral Doppler imaging underestimated or did not identify a residual outflow tract gradient in 17 patients. Left atrioventricular (AV) valve regurgitation after repair of complete AV septal defect was underestimated in three patients. Although intraoperative documentation of good ventricular function was usually associated with a good outcome, in three patients poor systemic ventricular function after cardiopulmonary bypass was not associated with early mortality. A minor degree of shunting around the patch was a common finding on epicardial and early postoperative imaging and persisted at the time of hospital discharge in 17 of 46 patients who had undergone patch closure of a ventricular septal defect as part of the surgical procedure. Additional trabecular septal defects were missed on color flow imaging after cardiopulmonary bypass in three patients, one of whom required subsequent reoperation. Although intraoperative two-dimensional and color flow imaging permitted the recognition of the majority of residual defects requiring immediate revision, residual outflow obstruction or AV valve regurgitation was usually underestimated. .A Sreeram N; Kaulitz R; Stumper OF; Hess J; Quaegebeur JM; Sutherland GR. .I 275544 .U 91010328 .S J Am Coll Cardiol 9101; 16(4):921-2 .M Echocardiography, Doppler/*; Heart Defects, Congenital/SU/*US; Human; Intraoperative Care/MT. .T Intraoperative echocardiography for congenital heart disease [editorial; comment] .P COMMENT; EDITORIAL. .A Guntheroth WG; Stevenson JG. .I 275545 .U 91010331 .S J Am Coll Cardiol 9101; 16(4):936-40 .M Aged; Angina Pectoris/*DT; Comparative Study; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Tolerance; Exercise Test; Human; Isosorbide Dinitrate/*AD/TU; Male; Middle Age; Support, Non-U.S. Gov't; Time Factors. .T The daylong pattern of the antianginal effect of long-term three times daily administered isosorbide dinitrate [see comments] .P JOURNAL ARTICLE. .W Three times daily administration of isosorbide dinitrate may avoid much of the tolerance seen with more frequent dosing. To determine the daylong pattern of the antianginal effect of three times daily isosorbide dinitrate, eight men with stable exertional angina and a positive exercise test were studied. The subjects had demonstrated increased exercise duration in response to oral isosorbide dinitrate therapy and absence of complete tolerance to long-term three times daily isosorbide dinitrate. Treadmill exercise to onset of angina was performed over 2 days at 8 AM, 9 AM, 11 AM, 1 PM, 2 PM, 4 PM, 6 PM and 7 PM. On one day each patient received isosorbide dinitrate at 8 AM, 1 PM and 6 PM in a previously titrated dose (mean 27.5 mg), which had been taken three times daily for at least 2 weeks. On the other day at the same hours each patient received double blind a placebo identical in appearance to isosorbide dinitrate. One hour after the 8 AM dose of isosorbide dinitrate, mean systolic blood pressure at rest had fallen by 19 mm Hg and mean exercise time to angina increased by 200 s. However, by 11 AM exercise time had returned to control level. One hour after the 1 PM dose of isosorbide dinitrate, exercise time increased by a mean of 150 s but was again at control level 2 h later.(ABSTRACT TRUNCATED AT 250 WORDS) .A Bassan MM. .I 275546 .U 91010333 .S J Am Coll Cardiol 9101; 16(4):943-7 .M Amiodarone/*AA/AN/*PK/TU; Chromatography, High Pressure Liquid; Coronary Disease/DT/SU; Heart Transplantation/*; Human; Male; Middle Age; Myocardium/*ME; Support, U.S. Gov't, P.H.S.. .T Myocardial amiodarone and desethylamiodarone concentrations in patients undergoing cardiac transplantation. .P JOURNAL ARTICLE. .W Myocardial amiodarone and desethylamiodarone concentrations were measured at multiple sites in the explanted heart in four patients who underwent cardiac transplantation. Patients were taking amiodarone, 200 to 400 mg/day (mean 300 +/- 115), for 88 to 428 days (mean 229 +/- 148). The mean cumulative dose was 58 +/- 21.3 g. Plasma amiodarone concentration in three subjects was 204, 312 and 419 ng/ml and desethylamiodarone concentration was 268, 513 and 880 ng/ml, respectively. Significant interindividual variability in myocardial concentrations of amiodarone and desethylamiodarone was observed (p less than 0.05). Mean myocardial amiodarone concentration ranged from 4 +/- 1.0 to 29 +/- 17.2 micrograms/g (p less than 0.05); mean desethylamiodarone concentration ranged from 22 +/- 8.8 to 141 +/- 102.5 micrograms/g (p less than 0.05). At each site, save for fat, myocardial desethylamiodarone concentration was higher than amiodarone concentration. Greater intraindividual variability was observed in myocardial desethylamiodarone compared with amiodarone concentration particularly in septal and scar tissue (p = NS). No significant relation was found between myocardial concentration and duration of treatment. In patients with significant ventricular disease, usefulness of plasma amiodarone and desethylamiodarone concentration to estimate myocardial concentration is limited by intra- and interindividual variability. .A Giardina EG; Schneider M; Barr ML. .I 275547 .U 91010334 .S J Am Coll Cardiol 9101; 16(4):948-56 .M Adult; Aged; Angina Pectoris/*DT; Angiotensin-Converting Enzyme Inhibitors/*TU; Benzazepines/*TU; Comparative Study; Coronary Disease/*DT; Delayed-Action Preparations; Double-Blind Method; Drug Therapy, Combination; Electrocardiography, Ambulatory; Exercise Test; Female; Human; Male; Metoprolol/AD/*TU; Middle Age; Support, Non-U.S. Gov't. .T Effects of benazepril and metoprolol OROS alone and in combination on myocardial ischemia in patients with chronic stable angina [see comments] .P JOURNAL ARTICLE. .W The efficacy of benazepril, metoprolol OROS and their combination was evaluated in 29 patients (42 to 74 years of age) with chronic stable angina and documented coronary artery disease in a placebo-controlled, double-blind, crossover trial using serial quantitated exercise testing and ambulatory electrocardiographic (ECG) monitoring. The mean (+/- SEM) exercise time was 8.5 +/- 0.7 min with placebo, 8.3 +/- 0.6 min (95% confidence interval [CI]-1.06 to 0.54) with benazepril, 9.4 +/- 0.5 min (95% CI -0.32 to 2.14) with metoprolol OROS and 9.6 +/- 0.5 min (95% CI -0.25 to 2.47) with the combination of benazepril and metoprolol OROS. The mean exercise time to the development of 1 mm ST segment depression was prolonged from 6.0 +/- 0.6 min with placebo to 6.3 +/- 0.6 min (95% CI -0.93 to 1.45) with benazepril, 7.9 +/- 0.5 min (95% CI 0.83 to 3.0) with metoprolol OROS and 8.1 +/- 0.6 min (95% CI 0.88 to 3.29) with the combination of benazepril and metoprolol OROS. Benazepril did not alter the rest or maximal heart rate, whereas metoprolol OROS alone and in combination significantly lowered the heart rate at rest and during maximal exercise. Systolic blood pressure at rest was nonsignificantly reduced, whereas diastolic blood pressure was lowered significantly by all treatments in comparison with placebo. At maximal exercise, only metoprolol OROS, whether given alone or in combination with benazepril, was able to blunt significantly systolic blood pressure and rate-pressure product.(ABSTRACT TRUNCATED AT 250 WORDS) .A Klein WW; Khurmi NS; Eber B; Dusleag J. .I 275548 .U 91010335 .S J Am Coll Cardiol 9101; 16(4):957-8 .M Angina Pectoris/*DT; Angiotensin-Converting Enzyme Inhibitors/*TU; Benzazepines/*TU; Comparative Study; Coronary Disease/*DT; Delayed-Action Preparations; Human; Metoprolol/AD/TU. .T Is there a role for angiotensin-converting enzyme inhibitors in the treatment of chronic myocardial ischemia? [editorial; comment] .P COMMENT; EDITORIAL. .A Abrams J. .I 275549 .U 91010336 .S J Am Coll Cardiol 9101; 16(4):959-66 .M Aged; Angioplasty, Transluminal, Percutaneous Coronary/*; Blood Substitutes; Comparative Study; Coronary Disease/*TH; Diastole/DE; Drug Combinations; Female; Fluorocarbons/*TU; Human; Male; Single-Blind Method; Support, Non-U.S. Gov't; Ventricular Function, Left/*DE. .T Does intracoronary infusion of Fluosol-DA 20% prevent left ventricular diastolic dysfunction during coronary balloon angioplasty? .P JOURNAL ARTICLE. .W Distal intracoronary infusion of the perfluorochemical Fluosol-DA 20% has been shown to prevent systolic dysfunction during coronary artery balloon occlusion in coronary angioplasty. To assess its effect on global diastolic dysfunction, a randomized, single-blind, crossover protocol comparing intracoronary infusion of Fluosol or no infusion (control) was performed during 60 s balloon inflations in 10 patients (mean age 67 years) undergoing coronary angioplasty. Assessment of global systolic and diastolic function was obtained with high fidelity micromanometer measurements of left ventricular pressure. Eighteen pairs of balloon inflations (Fluosol versus control) were analyzed. Patients reported significantly less severe chest pain during inflations accompanied by Fluosol compared with control. However, during coronary balloon occlusion, no significant differences in the changes from baseline values were observed between Fluosol and control with regard to ventricular relaxation, including the time constant of early ventricular relaxation (tau) and maximal rate of fall in left ventricular pressure (maximal negative dP/dt). No differences between Fluosol and control were observed in terms of the increase in end-diastolic pressure or minimal diastolic pressure during balloon inflation. Mean systolic pressure decrease from baseline values was greater during control than during Fluosol inflations (-9.0 +/- 3.3 mm Hg, p = 0.013), but no significant difference was observed in the change in maximal rate of rise in left ventricular pressure (maximal positive dP/dt). These results suggest that Fluosol does not preserve global left ventricular diastolic function during coronary balloon occlusion, possibly because of its limited oxygen delivery capability relative to arterial blood. .A Bell MR; Nishimura RA; Holmes DR Jr; Bailey KR; Schwartz RS; Vlietstra RE. .I 275550 .U 91010337 .S J Am Coll Cardiol 9101; 16(4):967-77 .M Animal; Captopril/AD/*TU; Comparative Study; Hemodynamics/*DE; Male; Myocardial Infarction/*DT/ET; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Time Factors. .T Early and late effects of captopril treatment after large myocardial infarction in rats. .P JOURNAL ARTICLE. .W The early (after 21 days) and late (after 4 months) effects of continuous treatment with captopril on left ventricular performance, weight and volumes were studied in rats with myocardial infarction. Early effects were examined in rats subjected to coronary ligation and randomized to either immediate treatment with captopril (2 g/liter drinking water) starting 2 h after surgery or no treatment. After 21 days, the treated group showed reductions in mean arterial, left ventricular systolic and left ventricular end-diastolic pressures compared with untreated rats. Right and left ventricular weight and left ventricular volumes were decreased and the ejection fraction index was increased by captopril treatment. To study the late effects of captopril, a second group of rats was randomized to immediate captopril treatment (starting 2 h after surgery), delayed captopril treatment (starting 21 days after surgery) or no treatment. When studied after 4 months of treatment, rats started on captopril treatment 2 h after infarction showed no differences compared with rats started on treatment 21 days after infarction. Treatment with captopril for 4 months produced changes that were similar to those in rats treated for 21 days. Captopril treatment improved hemodynamic function after myocardial infarction in rats examined after either 21 days or 4 months of treatment. The extent of the benefit was similar in the two treatment periods. Initiation of captopril therapy immediately after infarction did not appear to produce a greater effect than treatment started at 21 days after infarction in rats studied after the drug had been administered for 4 months. .A Gay RG. .I 275551 .U 91010338 .S J Am Coll Cardiol 9101; 16(4):978-85 .M Analysis of Variance; Animal; Comparative Study; Death, Sudden/*EP; Disease Models, Animal; Dogs; Electrocardiography; Exertion; Heart Rate/*PH; Male; Myocardial Infarction/MO/*PP; Prognosis; Risk Factors; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Ventricular Fibrillation/EP. .T Heart rate variability before and after myocardial infarction in conscious dogs at high and low risk of sudden death. .P JOURNAL ARTICLE. .W Heart rate variability has been demonstrated both experimentally and clinically to be of prognostic importance in determining mortality after myocardial infarction. However, no paired studies have been reported to examine heart rate variability before and after myocardial infarction. The hypothesis was tested that low values of heart rate variability provided risk assessment both before and after myocardial infarction with use of an established canine model of sudden cardiac death. Risk for sudden death was assessed 1 month after myocardial infarction by a protocol in which exercise and myocardial ischemia were combined; dogs that developed ventricular fibrillation were classified at high risk for sudden death (susceptible) and the survivors were considered low risk (resistant). In resistant dogs, myocardial infarction did not affect any measure of heart rate variability: 1) mean RR interval, 2) standard deviation of the mean RR interval, and 3) the coefficient of variance (standard deviation/RR interval). By contrast, after myocardial infarction, susceptible dogs showed significant decrease in all measures of heart rate variability. Before myocardial infarction, no differences were seen between susceptible and resistant dogs. However, 30 days after infarction, epidemiologic analysis of the coefficient of variance showed high sensitivity and specificity (88% and 80%, respectively), predicting susceptibility. Therefore, results of analysis of 30 min of beat to beat heart period at rest 30 days after myocardial infarction are highly predictive for increased risk of sudden death. .A Hull SS Jr; Evans AR; Vanoli E; Adamson PB; Stramba-Badiale M; Albert DE; Foreman RD; Schwartz PJ. .I 275552 .U 91010339 .S J Am Coll Cardiol 9101; 16(4):986-92 .M Analysis of Variance; Animal; Comparative Study; Dogs; Echocardiography/*MT/ST; Image Processing, Computer-Assisted/*; Myocardial Contraction/*PH; Observer Variation; Reference Standards; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Ventricular Function, Left/*PH. .T Echocardiographic definition of the left ventricular centroid. I. Analysis of methods for centroid calculation from a single tomogram. .P JOURNAL ARTICLE. .W Quantitation of myocardial contraction requires a frame of reference. Most investigators have sought a single reference frame per image, centered in some manner with respect to the mass of myocardium. Because there is no anatomic marker for the center of the heart, many different approaches have been pursued to identify a centroid of the left ventricle. The issue of whether the reference should be fixed throughout the cardiac cycle or float from image to image has been addressed in previous studies, but the more fundamental question of how a centroid can best be defined has not been answered. This study examines this basic issue by analysis of variance from observer to observer, cycle to cycle, animal to animal and method to method. Both endocardial and epicardial borders were digitized twice by each of two observers at 1/30 s intervals spanning the cardiac cycle for each of three cardiac cycles in six normal dogs. The left ventricular centroid was calculated by six methods: center of endocardial coordinates, center of epicardial coordinates, center of mid-myocardial (average) coordinates, center of endocardial area, center of epicardial area and center of mid-myocardial (average) area. The path of each centroid was correlated between observers and correlation coefficients were transformed for analysis of variance. This analysis indicates a best approach to centroid definition through distinct minimization of the variance: the best of the six methods proved to be center of endocardial area. .A Pearlman JD; Hogan RD; Wiske PS; Franklin TD; Weyman AE. .I 275553 .U 91010340 .S J Am Coll Cardiol 9101; 16(4):993-9 .M Animal; Comparative Study; Dogs; Echocardiography/*MT/ST; Image Processing, Computer-Assisted/*; Myocardial Contraction/PH; Myocardial Infarction/*US; Observer Variation; Reference Standards; Reproducibility of Results; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Systole/*PH; Ventricular Function, Left/*PH. .T Echocardiographic definition of the left ventricular centroid. II. Determination of the optimal centroid during systole in normal and infarcted hearts. .P JOURNAL ARTICLE. .W Although two-dimensional echocardiography is widely used in both clinical and experimental evaluations of regional cardiac wall motion, there is no established clinical method for quantitative analysis of the wall motion, not even for the normal radial motion observed in short-axis images. Measurement of radial wall motion requires determination of a centroid from which the radii emanate. Depending on its definition, the centroid is variously affected throughout systole by cardiac translation, regional wall motion and any shift of the subject position or transducer. A floating centroid is defined relative to the ventricular walls frame by frame, whereas a fixed centroid never moves with respect to the transducer. Evaluation of the best approach to definition of a centroid was previously presented (part I, this issue). The next question is how to use the centroid. This study examines which of four centroid applications provides the best reference for quantifying regional wall motion during systole. Method 1 is a floating centroid (defined separately for every image frame), method 2 uses the end-diastolic centroid as a fixed reference for all image frames, method 3 uses the end-systolic centroid as a fixed reference and method 4 uses the average as a fixed reference. Wall motion was measured with respect to each of these centroids by determining radial wall motion from end-diastole to end-systole and correlating radial motion throughout the cardiac cycle with that in normal control hearts.(ABSTRACT TRUNCATED AT 250 WORDS) .A Wiske PS; Pearlman JD; Hogan RD; Franklin TD; Weyman AE. .I 275554 .U 91010363 .S J Allergy Clin Immunol 9101; 86(3 Pt 1):279-87 .M Animal; Breast Feeding; Child, Preschool; Female; Human; Hypersensitivity/*ET/GE; IgE/IM; IgG/IM; Infant; Infant, Newborn; Pregnancy; Seasons; Smoking/AE; Virus Diseases/CO. .T Environmental factors versus genetic determinants of childhood inhalant allergies. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .A Ownby DR. .I 275555 .U 91010364 .S J Allergy Clin Immunol 9101; 86(3 Pt 1):292-305 .M Adolescence; Adult; Aged; Animal; Asthma/*TH; Child; Child, Preschool; Dust/AE; Human; Immunotherapy/*/AE; Infant; Middle Age; Mites/IM. .T Specific immunotherapy in asthma. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .A Bousquet J; Hejjaoui A; Michel FB. .I 275556 .U 91010365 .S J Allergy Clin Immunol 9101; 86(3 Pt 1):306-13 .M Adult; Antigens/*IM; Asthma/*ME; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid/ME; Eosinophils/IM; Female; Forced Expiratory Volume; Histamine/AN; Human; Immunoglobulins/AN; Inflammation/*ME; Male; Neutrophils/IM; Oxygen/*ME; Proteins/AN; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Enhanced reactive oxygen species metabolism of airspace cells and airway inflammation follow antigen challenge in human asthma. .P JOURNAL ARTICLE. .W Airflow limitation and airway inflammation follow antigen bronchoprovocation in sensitized individuals. Inflammation likely results from the interplay of several previously demonstrated factors, but the participation and persistence of enhanced reactive oxygen species (ROS) metabolism of airspace cells after antigen challenge have received more limited attention. We studied nine subjects with mild asthma by bronchoalveolar lavage before and 48 (one subject) to 72 (eight subjects) hours after antigen bronchoprovocation and compared airspace cell numbers and types, cell function, and bronchoalveolar lavage fluid protein, albumin, and immunoglobulins. Mild, but significant, airflow limitation persisted at the time of the second lavage. Eosinophil influx was a notable component of the increased airspace cells in postchallenge lavages. Airspace cells demonstrated significantly enhanced ROS metabolism, and total protein, albumin, and IgM levels were higher in postchallenge lavage specimens. Antigen bronchial challenge produces airspace inflammation, which may develop, in part, as a consequence of enhanced ROS metabolism of airspace cells. .A Calhoun WJ; Bush RK. .I 275557 .U 91010366 .S J Allergy Clin Immunol 9101; 86(3 Pt 1):314-20 .M Adult; Chemotaxis, Leukocyte/*DE; Eosinophils/*DE/IM; Female; Histamine H1 Receptor Blockaders/*PD; Human; Hydroxyzine/*AA/PD; Male; Platelet Activating Factor/*PD; Skin/*DE; Skin Tests. .T In vivo effects of cetirizine on cutaneous reactivity and eosinophil migration induced by platelet-activating factor (PAF-acether) in man. .P JOURNAL ARTICLE. .W The aim of the study was to determine the effect of cetirizine, a new potent H1 antihistamine, on acute cutaneous inflammatory response and eosinophil accumulation induced in vivo by platelet-activating-factor (PAF-acether) and allergen. In a double-blind, crossover study, seven subjects allergic to grass pollen and three nonallergic control subjects received orally either cetirizine, 20 mg/day, or placebo for 4 days. On day 4, the subjects were skin tested with grass pollen and PAF-acether (400 and 40 ng per site). After the challenge, an evaluation of time-course cutaneous eosinophil infiltrations by a skin window technique was performed. Cetirizine pretreatment reduced skin wheal and erythema elicited by allergen and PAF, 400 and 40 ng, by 74.6% (p less than 0.001), 53.9% (p less than 0.001), and 47% (p less than 0.01), respectively. Skin reactivity induced by PAF-acether was also significantly reduced by cetirizine in nonallergic subjects. Cetirizine reduced at hour 24 eosinophil infiltrations induced by allergen and PAF, 400 and 40 ng, by 63% (p less than 0.001), 58.5% (p less than 0.001), and 57.8% (p less than 0.01), respectively. This inhibitory effect of cetirizine on allergen and PAF-induced eosinophil infiltration was already effective 2 hours after the challenge. PAF induced a nonsignificant eosinophil influx in all nonallergic subjects. In conclusion, cetirizine inhibited both the immediate cutaneous response and the eosinophil influx induced by allergen and by a potent eosinophil chemotactic factor, such as PAF-acether. Therefore, cetirizine, besides its anti-H1 effect, has the potential to modulate the allergic inflammatory response. .A Fadel R; David B; Herpin-Richard N; Borgnon A; Rassemont R; Rihoux JP. .I 275558 .U 91010368 .S J Allergy Clin Immunol 9101; 86(3 Pt 1):325-32 .M Adolescence; Adult; Aged; Anaphylaxis/*ET/TH; Anesthesia, General/*AE; Child; Child, Preschool; Female; Follow-Up Studies; Human; IgE/IM; Male; Middle Age; Preanesthetic Medication; Skin Tests. .T Anaphylaxis during induction of general anesthesia: subsequent evaluation and management. .P JOURNAL ARTICLE. .W Twenty-seven patients were referred for evaluation of anaphylaxis after induction of general anesthesia (GA) in which thiobarbiturates, muscle relaxants, or antibiotics were administered intravenously. Skin testing by the prick and intracutaneous methods was performed with dilutions of the thiobarbiturates and muscle relaxants; beta-lactam reagents were used in patients who had also received these drugs. No skin test reactivity was noted in 16 normal subjects. Skin tests were positive in 13 patients (thiobarbiturates in five, muscle relaxants in six, and antibiotics in two patients). Two patients were dermatographic and yielded indeterminate skin test results. Eleven of the 27 patients subsequently had GA; all patients received a premedication regimen of prednisone and diphenhydramine. Of three patients with negative skin tests, one experienced an arrhythmia, but no other signs attributable to anaphylaxis were noted. One patient with dermatographism had GA without a reaction. Positive skin tests implicated an agent that was avoided in seven patients; one of these patients experienced delayed urticaria/angioedema after the completion of GA. Thus, no patients developed anaphylaxis during subsequent GA for which agents producing positive skin tests were avoided, and a premedication regimen was used. .A Moscicki RA; Sockin SM; Corsello BF; Ostro MG; Bloch KJ. .I 275559 .U 91010369 .S J Allergy Clin Immunol 9101; 86(3 Pt 1):333-44 .M Adult; Antigens, Differentiation, B-Lymphocyte/*AN/PH; Antigens, Differentiation, T-Lymphocyte/AN; B-Lymphocytes/*IM; Cells, Cultured; Human; IgE/*BI; Interleukin-4/*PD; Killer Cells, Natural/IM; Middle Age; Receptors, Fc/*AN/PH. .T Soluble CD23 containing B cell supernatants induce IgE from peripheral blood B-lymphocytes and costimulate with interleukin-4 in induction of IgE. .P JOURNAL ARTICLE. .W The role of soluble fragments of CD23 and their relationship to interleukin-4 (IL-4) in the in vitro production of IgE by normal human peripheral blood mononuclear cells was examined. Most donors' cells were induced to produce IgE in vitro by IL-4 during a 9- to 21-day culture. This stimulation was not observed in the absence of T cells. Inability of IL-4 to induce IgE in nonresponding cultures was associated with a failure to express CD23 on Lev-19+ natural killer cells; CD23 expression on B cells and monocytes was equivalent in responding and nonresponding subjects. Concentrated supernatants from Epstein-Barr virus-transformed B cell lines containing soluble fragments (sCD23) of the low-affinity Fc epsilon R (Fc epsilon R-II, CD23) induced IgE from all donors' cells in the absence of T cells. The sCD23 containing supernatants were demonstrated to be devoid of IL-4, and their effect could not be abrogated by anti-IL-4. IgE induction by both IL-4 and sCD23-containing supernatant were blocked by anti-CD23 monoclonal antibody. Affinity absorption of sCD23 removed the IgE-inducing activity. The cells most responsive to the sCD23 material were small, resting B cells rather than large in vivo activated cells. IL-4 synergized with sCD23-containing supernatant in the T cell-depleted cultures, and limiting dilution analyses demonstrated that IL-4 caused a more than tenfold increase in the precursor frequency of cells capable of responding to sCD23-containing supernatant with IgE production. These data are consistent with the hypothesis that IL-4 has multiple effects in the ultimate induction of human IgE including (1) commitment of B cells to IgE and (2) the generation of natural killer cell sCD23 fragments that subsequently drive IgE-committed cells to IgE synthesis. .A Saxon A; Ke Z; Bahati L; Stevens RH. .I 275560 .U 91010371 .S J Allergy Clin Immunol 9101; 86(3 Pt 1):353-9 .M Adenosine/SE; Adenosine Monophosphate/*PD/TU; Administration, Inhalation; Adolescence; Adult; Asthma/*PP; Asthma, Exercise-Induced/*DT; Bronchoconstriction/*DE; Female; Forced Expiratory Volume; Histamine/PD; Human; Male. .T Repeated exposure of asthmatic airways to inhaled adenosine 5'-monophosphate attenuates bronchoconstriction provoked by exercise. .P JOURNAL ARTICLE. .W Inhaled adenosine 5'-monophosphate (AMP) induces bronchoconstriction in subjects with asthma, probably caused by histamine release from airway mast cells, and repeated AMP bronchial challenge leads to attenuation of the bronchoconstrictor response. Since exercise-induced bronchoconstriction may be mediated by hypertonic mast cell degranulation, we postulated that repeated AMP bronchial challenge should reduce the response to subsequent exercise challenge. Eight atopic subjects with asthma took part in an unblinded, randomized trial. On the control study day, a treadmill exercise test previously demonstrated to induce a greater than 20% fall in FEV1 was performed. On the AMP study day, three AMP dose-response bronchial challenges were performed at 1-hour intervals. Each AMP challenge was continued until either a provocative concentration causing a 20% fall in FEV1 had been achieved (PC20) and the PC20 was calculated, or the maximum concentration of AMP (400 mg/ml) had been administered. After recovery of the FEV1 from AMP challenge, a treadmill exercise test identical to the test on the control study day was performed. On the AMP study day, the geometric mean PC20 was 15.3 (7.9 to 29.5) mg/ml for the first test, and 28.2 (10.7 to 77.4) mg/ml for the third test (not significant). On the control study day, the mean maximum percentage fall in FEV1 after exercise was 28.0% +/- 2.7%, whereas on the AMP study day, it was reduced to 13.0% +/- 4.3% (p less than 0.01). A significant correlation was found between the change in responsiveness to AMP induced by repeated challenge and the attenuation of the subsequent exercise response (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) .A Finnerty JP; Polosa R; Holgate ST. .I 275561 .U 91010372 .S J Allergy Clin Immunol 9101; 86(3 Pt 1):360-70 .M Administration, Oral; Adrenal Cortex Hormones/AD/*PD; Antigens/*IM; Basophils/ME; Codeine/PD; Comparative Study; Histamine Liberation/*; Human; Peptide Hydrolases/*SE; Prostaglandin D2/*SE; Skin/*SE; Support, U.S. Gov't, P.H.S.. .T In vivo antigen-induced cutaneous mediator release: simultaneous comparisons of histamine, tryptase, and prostaglandin D2 release and the effect of oral corticosteroid administration. .P JOURNAL ARTICLE. .W To determine if basophils were responsible for the persistent release of histamine during continuous antigen (Ag) administration in the skin, we compared the release of histamine, tryptase, and prostaglandin D2 (PGD2) at sites of continuous (5 hours) and intermittent Ag and codeine skin-chamber challenge in the skin of 16 atopic and four nonatopic subjects. In addition, we compared the release of these three mediators at sites of continuous Ag challenge in five subjects during oral administration of 1 mg/kg of methylprednisolone. Continuous Ag challenge induced an initial (first hour) peak of histamine release followed by a lower level plateau of histamine release during the next 4 hours. The level of histamine release during the second to fifth hours was significantly higher at these sites of continuous Ag challenge than at the codeine- or intermittent Ag-challenge sites. Levels of both tryptase and PGD2 were increased after the first hour of Ag or codeine challenge, and tryptase decreased progressively thereafter at all sites. In corticosteroid-treated subjects, the persistent histamine release during the second to fifth hours of Ag challenge was significantly reduced. In contrast, corticosteroid therapy did not affect histamine release during the first hour of Ag challenge nor the release of PGD2 or tryptase at any time period. These findings suggest that basophils are the source of the persistent histamine release at sites of continuous in vivo Ag challenge, since such release (1) was unaccompanied by release of tryptase or PGD2 (released from mast cells but not basophils), (2) did not occur after codeine challenge that activates mast cells but not basophils, and (3) was inhibited by steroids that inhibit the accumulation and release of histamine from basophils but not mast cells. .A Atkins PC; Schwartz LB; Adkinson NF; von Allmen C; Valenzano M; Zweiman B. .I 275562 .U 91010373 .S J Allergy Clin Immunol 9101; 86(3 Pt 1):371-9 .M Adolescence; Adult; Antigens/IM; Basophils/ME; Codeine/PD; Female; Histamine Liberation/*; Human; Hypersensitivity/*ME; Male; Skin/*SE; Skin Tests; Support, U.S. Gov't, P.H.S.. .T Determinants of in vivo histamine release in cutaneous allergic reactions in humans. .P JOURNAL ARTICLE. .W To determine host factors influencing the magnitude of mediator release during ongoing cutaneous allergic reactions in humans, we compared, in 22 subjects, the first-hour, second- to fifth-hour, and total (0 to 5 hours) skin chamber histamine release to (1) the in vitro reactivity and sensitivity of basophils to antigen for histamine release and (2) skin test sensitivity and reactivity to antigen, histamine, and codeine. There was no significant correlation between the first-hour and second- to fifth-hour histamine release. With a combination of basophil, antigen, histamine, and codeine skin sensitivity and reactivity, 64% to 75% of the magnitude of the first-hour, second- to fifth-hour, and total (0 to 5 hours) skin chamber histamine release could be accounted for. We conclude that antigen-induced in vivo allergic responses are a complex phenomenon dependent, in part, on antigen sensitivity, basophil and mast cell reactivity, and end organ responsiveness to mediators. .A Atkins PC; von Allmen C; Valenzano M; Olson R; Shalit M; Zweiman B. .I 275563 .U 91010374 .S J Allergy Clin Immunol 9101; 86(3 Pt 1):380-6 .M Adolescence; Adult; Aerosols; Beclomethasone/*AD/AE; Child; Comparative Study; Drug Administration Schedule; Female; Hay Fever/*DT; Human; Male; Support, Non-U.S. Gov't. .T Aqueous beclomethasone diproprionate nasal spray: regular versus "as required" use in the treatment of seasonal allergic rhinitis. .P JOURNAL ARTICLE. .W OBJECTIVE: to determine the effect of alternative regimens of nasal steroid administration on symptoms and quality of life. DESIGN: randomized, double-blind, parallel-group comparison. SUBJECTS: sixty ragweed-sensitive adults recruited from participants of previous studies and through media advertising. INTERVENTIONS: 200 micrograms of aqueous beclomethasone diproprionate nasal spray, twice daily, from 1 week before until 1 week after the ragweed-pollen season (regular) or 100 micrograms of the spray, taken as required, up to 400 micrograms daily; troublesome nasal symptoms were treated, in both groups, by increasing the daily dose to 800 micrograms until symptoms were controlled. If this treatment was insufficient, 120 mg of terfenadine, daily, was added. RESULTS: One subject in the "as required"-treated group withdrew with uncontrolled nasal symptoms. In the remaining subjects, sneezing, stuffy nose, and rhinorrhea, measured by a daily diary, were significantly better controlled in the regular-treated group (p less than 0.025). Impairment of quality of life, including sleep disturbance, nonhay fever symptoms, practical problems, and uncomfortable emotions were greater in the as required-treated group (p less than 0.001). Subjects in the regular-treated group required less additional terfenadine (0.27 tablets per subject versus 1.40; p = 0.022). Eye symptoms and eye-drop use were similar in the two treated groups. CONCLUSION: In patients with seasonal allergic rhinitis, regular use of inhaled steroids results in fewer symptoms and better quality of life than when the spray is taken only as required. .A Juniper EF; Guyatt GH; O'Byrne PM; Viveiros M. .I 275564 .U 91010375 .S J Allergy Clin Immunol 9101; 86(3 Pt 1):387-92 .M Adult; Animal; Antibodies/*AN; Double-Blind Method; Female; Food Hypersensitivity/*IM; Human; IgE/AN; IgG/*CL; Intradermal Tests; Male; Middle Age; Shrimp/*IM; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T The relationships among shrimp-specific IgG subclass antibodies and immediate adverse reactions to shrimp challenge. .P JOURNAL ARTICLE. .W High levels of shrimp-specific IgE, in association with a positive prick test, are not always predictive of a positive, immediate response to double-blind, placebo-controlled, food challenge (DBPCFC) with shrimp. The observation that shrimp-sensitive individuals in general have increased levels of circulating shrimp-specific IgG is of interest because antigen/allergen-specific IgG subclasses have been associated with adverse reactions to foods. Therefore, this current study measured shrimp-specific IgG subclass and IgE antibodies in 31 individuals with histories of immediate, adverse reactions to shrimp immediately before DBPCFC and 20 shrimp-tolerant subjects. Individuals with a history of shrimp sensitivity had significantly raised shrimp-specific IgG2 and IgG4 compared to shrimp-tolerant individuals. Challenge-positive subjects were distinguished from subjects with negative or equivocal responses by an increased IgG2 (p less than or equal to 0.001). Specific IgG4 was not raised (p less than or equal to 0.065). These studies indicate that some shrimp-specific IgG subclass levels are increased in shrimp-sensitive subjects. However, none of the subclass responses were significantly predictive of a positive response to DBPCFC and therefore were not diagnostic of shrimp intolerance. .A Morgan JE; Daul CB; Lehrer SB. .I 275565 .U 91010376 .S J Allergy Clin Immunol 9101; 86(3 Pt 1):393-9 .M Antibodies/*AN; Comparative Study; Detergents; Enzyme-Linked Immunosorbent Assay; Human; IgE/*AN; Occupational Exposure/*; Radioallergosorbent Test; Skin Tests; Subtilisins/*IM. .T ELISA for human IgE antibody to subtilisin A (Alcalase): correlation with RAST and skin test results with occupationally exposed individuals. .P JOURNAL ARTICLE. .W An ELISA was developed to detect specific IgE antibody to the Bacillus subtilis-derived proteolytic detergent enzyme, subtilisin A (Alcalase), in sera from exposed detergent workers. Workers in the detergent industry are exposed via inhalation to low levels of the enzyme dust in the presence of detergent dust. Chemically inactivated Alcalase was used as the test antigen. Significant binding of IgE antibody to the immobilized enzyme was detected in the ELISA. The binding of allergic antibody to Alcalase was specifically inhibited in a dose-dependent manner by preincubating sera with 0.1 to 100 micrograms of inactivated Alcalase. Binding of IgE antibody to Alcalase could not be inhibited by two other inactivated bacterial proteases, Savinase and Esperase, derived from different Bacillus species. ELISA and skin test results demonstrated total agreement for 27 of 31 samples (87%), whereas RAST and skin test results demonstrated total agreement for only 24 of 31 samples (77%), indicating that the ELISA was more sensitive than the RAST. We conclude that the ELISA is a sensitive, fast, alternative to the RAST for detection of Alcalase-specific IgE antibody in detergent enzyme-exposed workers. .A Sarlo K; Clark ED; Ryan CA; Bernstein DI. .I 275566 .U 91010377 .S J Allergy Clin Immunol 9101; 86(3 Pt 1):400-7 .M Child; Eosinophilia/*EP; Female; Human; IgE/*AN; Male; Prevalence; Sex Factors; Support, Non-U.S. Gov't; Tobacco Smoke Pollution/*AE. .T Increased serum IgE and increased prevalence of eosinophilia in 9-year-old children of smoking parents. .P JOURNAL ARTICLE. .W We studied the relationship of serum IgE levels and eosinophil counts with passive smoking in 9-year-old, nonselected children from three Italian towns near Rome. Male children of smoking parents had a significantly higher total count and percentage of eosinophils (p = 0.008) and higher IgE levels (p = 0.01) than male children of nonsmoking parents. Prevalence of eosinophilia (defined as greater than or equal to 4% of total white blood cell count) was significantly correlated with the number of cigarettes smoked by parents among boys (p = 0.003) but not among girls (p = 0.20). There was a significant trend (p = 0.008) for prevalence of eosinophilia to increase with increasing levels of serum IgE. For any given level of serum IgE, the frequency of eosinophilia was higher among children of smoking parents than among children of nonsmoking parents. When parental smoking was studied in a multivariable analysis and after controlling for the other variable, it was still significantly associated with eosinophilia in the children of these smoking parents but not with serum IgE levels. We conclude that parental smoking is associated with a significant enhancement of the expression of the most important markers of allergic sensitization in the children of smoking parents. This is particularly evident for boys and may explain, at least in part, the increased frequency of respiratory symptoms in children of smoking parents. .A Ronchetti R; Macri F; Ciofetta G; Indinnimeo L; Cutrera R; Bonci E; Antognoni G; Martinez FD. .I 275567 .U 91010378 .S J Allergy Clin Immunol 9101; 86(3 Pt 1):407-11 .M Adrenergic Beta Receptor Blockaders/*AE; Adult; Allergens/*IM; Desensitization, Immunologic/*AE; Female; Human; Male; Risk. .T Risk of systemic reactions in patients taking beta-blocker drugs receiving allergen immunotherapy injections. .P JOURNAL ARTICLE. .W To learn whether patients taking beta-blocker (BB) drugs were at increased risk of having systemic reactions (SRs) from allergen immunotherapy, we prospectively studied 56,105 injection visits in 3178 patients during a 1-year interval. A total of 166 SRs occurred in 144 patients (4.5% of all patients) or 3.0 SRs occurred per 1000 injection visits. Sixty-eight patients were taking BB drugs throughout the year, and only one patient had an SR. By chance, 3.08 patients were expected to have had SRs. We conclude that BB drugs did not increase the frequency of SRs in the patients studied who were receiving immunotherapy (p greater than 0.95). Patients taking BB drugs may still be at increased risk, however, from more severe SRs or their SRs may be more refractory to therapy. .A Hepner MJ; Ownby DR; Anderson JA; Rowe MS; Sears-Ewald D; Brown EB. .I 275568 .U 91010379 .S J Allergy Clin Immunol 9101; 86(3 Pt 1):415 .M Bronchitis/*ET; Eosinophilia/*ET; Female; Human; Rhinitis/*ET; Syndrome. .T Nonatopic rhinitis and bronchitis with eosinophilia syndrome [see comments] .P JOURNAL ARTICLE. .A Kentor PM. .I 275569 .U 91010380 .S J Allergy Clin Immunol 9101; 86(3 Pt 1):416-7 .M Adult; Case Report; Human; Hydroxylamines/TO; In Vitro; Lymphocytes/*DE; Male; Sulfamethoxazole/*ME; Support, Non-U.S. Gov't; Trimethoprim-Sulfamethoxazole Combination/*AE. .T Severe multisystem disease caused by trimethoprim-sulfamethoxazole: possible role of an in vitro lymphocyte assay. .P JOURNAL ARTICLE. .A Epstein M; Wright JM. .I 275570 .U 91010381 .S J Allergy Clin Immunol 9101; 86(3 Pt 1):418-9 .M Adult; Female; Histamine/PD; Human; Male; Middle Age; Neoplasms/*IM; Platelet Activating Factor/*PD; Skin/*DE. .T Decreased skin response to intradermal platelet-activating factor (PAF-acether) in cancer patients. .P JOURNAL ARTICLE. .A Burtin C; Noirot C; Scheinmann P; Paupe J; Benveniste J. .I 275571 .U 91010382 .S J Allergy Clin Immunol 9101; 86(3 Pt 1):420 .M Animal; Cats/*IM; Human; Hypersensitivity/*PC; Vitamin E/*PD. .T Cat-allergen sensitivity [letter; comment] .P COMMENT; LETTER. .A Cathcart RF 3d. .I 275572 .U 91010383 .S J Allergy Clin Immunol 9101; 86(3 Pt 2):421-42 .M Clinical Trials; Food Additives/*AE; Food Hypersensitivity/*; Human; Research Design/*. .T Workshop on experimental methodology for clinical studies of adverse reactions to foods and food additives. .P MEETING REPORT. .I 275573 .U 91010384 .S J Am Diet Assoc 9101; 90(10):1370-2 .M Adult; Diet, Reducing/*; Female; Human; Nutrition/*; Obesity/*DH; Weight Loss/*. .T Weight loss study provokes comment [letter] .P LETTER. .I 275574 .U 91010385 .S J Am Diet Assoc 9101; 90(10):1383-6 .M Cholesterol, Dietary/*AD; Coronary Disease/*PC; Costs and Cost Analysis; Counseling; Dietary Services/*; Human; Hypercholesterolemia/*DH. .T Bringing the cholesterol message to the public: dietitians must be proactive in nutrition counseling. .P JOURNAL ARTICLE. .A Yetiv JZ; Del Tredici AM. .I 275575 .U 91010386 .S J Am Diet Assoc 9101; 90(10):1387-92 .M Adult; Aged; Aged, 80 and over; Body Mass Index; Caloric Intake; Cholesterol/BL; Cholesterol, Dietary/AD; Cross-Sectional Studies; Diet Records; Eating; Female; Homeless Persons/*; Human; Male; Middle Age; New York City; Nutrition Surveys/*; Nutritional Status/*; Urban Population/*. .T Health and nutrition survey in a group of urban homeless adults. .P JOURNAL ARTICLE. .W Homeless persons eat foods from municipal and privately run shelters, fast-food restaurants, delicatessens, and garbage bins. Data on the adequacy of the diets and the nutritional status of homeless persons are sparse. Therefore, we surveyed the nutritional adequacy of the dietary intake, the quality of shelter meals, and objective clinical parameters indicative of nutritional status in a heterogeneous group of urban homeless persons. The group comprised mentally ill persons, alcohol and illicit drug users, and temporarily unemployed persons. Although 86 of the 96 subjects (90%) in our survey reported that they obtained enough to eat, a low dietary adequacy score, which was based on the basic four food groups, of 10.7 (norm = 16) indicated that the quality of their diets was inadequate. Shelter meals and diet records showed a high level of saturated fat and cholesterol. Serum cholesterol levels above the desirable limit of 5.17 mmol/L (200 mg) were observed in 79 subjects (82%). In addition to a prevalence of hypertension and obesity (observed in 37 subjects [39%], these homeless persons were at high risk for development of or worsening of cardiovascular disease. We conclude that homeless persons who obtain meals at shelters are getting enough to eat. However, the shelter meals should be modified to meet the nutritional needs and dietary prescriptions of the large number of clients who suffer from various health disorders. .A Luder E; Ceysens-Okada E; Koren-Roth A; Martinez-Weber C. .I 275576 .U 91010387 .S J Am Diet Assoc 9101; 90(10):1393-7 .M Comparative Study; Dietary Services/*; Dietetics/*MT/ST; Female; Human; Internship, Nonmedical/*; Male; Nutritional Status; Patient Care Planning/*; Students, Health Occupations/*; Support, Non-U.S. Gov't. .T Nutrition care planning: comparison of the skills of dietitians, interns, and students. .P JOURNAL ARTICLE. .W A written case study--or patient management problem--was used to examine how the nutrition care planning process is influenced by increasing clinical experience. The sample consisted of 45 students in diet therapy courses, 46 dietetic interns, and 44 experienced clinical or generalist dietitians. The patient management problem tested data gathering, with sections containing information needed to assess nutritional status, and nutrition care planning, in which subjects identified and evaluated problems and selected short- and long-term goals. Performance was scored by comparing subjects' answers with those of five dietetic experts. Dietitians scored highest and students scored lowest on efficiency of data gathering. Dietitians and interns scored higher than students on proficiency of data gathering and nutrition care planning. Overall, dietitians and interns performed better than students. Only in tasks requiring the highest levels of information processing and/or confidence in clinical judgment were differences between dietitians and interns consistently found. These findings demonstrate that basic nutrition care planning skills are acquired during dietetic internships, but advanced skills are added with clinical experience. .A Gates GE; Kris-Etherton PM; Greene G. .I 275577 .U 91010388 .S J Am Diet Assoc 9101; 90(10):1398-401 .M Adult; Educational Status/*; Female; Food Services/*; Human; Job Satisfaction/*; Male; Middle Age; Questionnaires; Software. .T The effect of education on foodservice manager job satisfaction. .P JOURNAL ARTICLE. .W We conducted a study to determine whether educational background (field of study and level of education) was related to the job satisfaction of foodservice managers. The Index of Organizational Reactions Questionnaire was used to measure specific components of job satisfaction based on a five-point Likert-style scale (1 = low satisfaction, 3 = moderate satisfaction, and 5 = high satisfaction). Questionnaires were mailed to the entire population of 256 foodservice managers employed in college and university dining facilities of a regional division of a major foodservice company in the northeastern United States. Names, titles, positions, and addresses of the managers were obtained from the company's human resources department. Analysis of data was done through computation of the point-biserial correlation coefficient and the rank order correlation coefficient. Managers who responded to the questionnaire (74.6%) indicated moderate overall job satisfaction (mean = 3.42 on a 5-point scale). Of the respondents, 44% had an educational background in foodservice; these respondents had lower overall job satisfaction than did those having no education/training in foodservice. Both groups were most satisfied with the job components of supervision, type of work, and relationship with coworkers. Both groups were least satisfied with pay and benefits, company identification, and amount of work. A significant (p less than .01) positive relationship was found between educational field of study and job satisfaction, and a significant (p less than .001) negative relationship was found between educational level (i.e., degree[s] earned) and job satisfaction.(ABSTRACT TRUNCATED AT 250 WORDS) .A Kuntz KA; Borja ME; Loftus MK. .I 275578 .U 91010389 .S J Am Diet Assoc 9101; 90(10):1402-4, 1407 .M Adult; Analysis of Variance; Diet Records/*; Eating/*; Human; Nutrition/*ED. .T Improved accuracy of estimating food quantities up to 4 weeks after training. .P JOURNAL ARTICLE. .W Subjects from a large introductory nutrition course were divided into two groups, one that received training on estimating food quantities and one that received no instruction. Training consisted of 10-minute sessions during which subjects passed around and viewed 10 food models labeled with their respective quantities. The trained subjects estimated quantities of six real foods at one of three points in time: immediately after training, 1 week later, or 4 weeks later. Untrained subjects estimated quantities of the same six foods. For all foods combined, trained subjects gave significantly better estimates than untrained subjects, whether estimates were made immediately after training, 1 week later, or 4 weeks later. The estimates of the trained subjects on the day of training and 1 week later were not significantly different, but both were significantly better than estimates made 4 weeks later. In regard to individual food items, trained subjects estimating immediately or 1 week later were always more accurate than untrained subjects. Effects of training disappeared by week 4 for three of the six foods. These results support the use of training, with food models, to improve an individual's ability to estimate food quantities accurately and indicate that the impact of such training lasts for at least 1 week and can last up to 4 weeks. The findings imply that training with periodic reviews may be necessary in a clinical setting to ensure that patients estimate their food consumption accurately. .A Bolland JE; Ward JY; Bolland TW. .I 275579 .U 91010390 .S J Am Diet Assoc 9101; 90(10):1408-14, 1017 .M Cholesterol, Dietary/*AD; Dietary Fats/*AD; Health Promotion/*MT; Human; Hyperlipidemia/*DH; Patient Compliance/*; Support, U.S. Gov't, P.H.S.. .T Promoting adherence to low-fat, low-cholesterol diets: review and recommendations. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Evidence that lowering blood cholesterol levels reduces risk of coronary heart disease has prompted widespread recommendations that hyperlipidemic individuals undergo dietary therapy. However, the extent to which people can adopt and maintain diets to lower lipids is unclear. In our article, we review what is currently known regarding adherence to low-fat diets and present an approach to dietary counseling for lowering cholesterol that incorporates elements of behavioral self-management and social learning theory. We discuss specific recommendations for counseling hyperlipidemic patients based on the Dietary Alternatives Study. Recommendations include providing patients with an adequate knowledge base to make dietary changes, using goal setting and self-monitoring to help patients initiate dietary changes, enlisting support from the patient's family, and enhancing self-efficacy to promote long-term dietary maintenance. .A McCann BS; Retzlaff BM; Dowdy AA; Walden CE; Knopp RH. .I 275580 .U 91010391 .S J Am Diet Assoc 9101; 90(10):1418-22 .M Counseling/*ST; Dietary Services/*ST; Dietetics/*ST; Human; Internship, Nonmedical/*ST; Nutrition/*ED; Questionnaires. .T Nutrition education and counseling: knowledge and skill levels expected by dietetic internship directors. .P JOURNAL ARTICLE. .W Development of nutrition education and counseling skills is important in the educational preparation of dietitians. A national survey of dietetic internship directors was conducted to determine competency levels expected of students at the start of an internship, internship training given, and further preparation students need in 32 knowledge/skills areas deemed essential for delivery of nutrition education and counseling services. Completed questionnaires were received from 66 of 102 (65%) internship directors surveyed. The majority of directors expected only basic preparation for group nutrition education and individual counseling knowledge/skills areas. Internship training in nutrition education competencies was "moderate" to "extensive," whereas preparation in nutrition counseling competencies was more likely to be "extensive." Directors perceived the internship to provide adequate preparation in all but the advanced practice skills, such as behavior modification and motivational strategies, for which further preparation was recommended. The majority of internship directors reported that more than 25% of the intern practice experience was in patient counseling, with less experience in group instruction. Implications for undergraduate dietetic education are discussed in relation to internship directors' expectations as well as to present and future trends in the dietetic profession. .A Sullivan BJ; Schiller MR; Horvath MC. .I 275581 .U 91010392 .S J Am Diet Assoc 9101; 90(10):1423-6 .M Adult; Child Health Services/*ST; Child Nutrition/*; Child, Preschool; Dietary Services/ST; Female; Human; Infant; Maternal Health Services/*ST; Nutrition/*; Nutritional Status; Pregnancy; Quality Control; State Health Planning and Development Agencies/*ST; Support, U.S. Gov't, P.H.S.; United States. .T Capacity of state health agencies to meet nutrition objectives in maternal and child health. .P JOURNAL ARTICLE. .W Public health nutritionists in 54 official state health agencies were surveyed in 1987 to determine to what extent they were prepared to implement the Model State Nutrition Objectives developed by the Association of State and Territorial Public Health Nutrition Directors. Objectives related to services to the maternal and child health (MCH) population were the focus of one part of the survey. One half of all states have plans for nutrition services integrated into their state MCH plans. More than 75% of state agencies collect data on the nutritional status of pregnant and lactating women, infants, and preschool children. Fewer than half collect data on dietary intake patterns or nutrition knowledge. Thirty-one agencies reported a formal quality assurance program for one or more subsets of the MCH population. At least 75% of all states provide dietary intake recommendations, screening and assessment protocols, and policies concerning referrals to maternal and infant health programs. State health agencies are already involved in activities that will facilitate adoption of the model state nutrition objectives. .A Thompson EB; Bellamy MM; Kaufman M; Jarka E. .I 275582 .U 91010393 .S J Am Diet Assoc 9101; 90(10):1427-8 .M Adult; Blood Pressure; Cardiovascular Diseases/*EP/PC; Cholesterol/BL; Female; Florida/EP; Follow-Up Studies; Health Behavior; Health Promotion/*; Human; Male; Occupational Health Services/*; Risk Factors; Weight Loss. .T Cardiovascular risk changes in a work-site health promotion program. .P JOURNAL ARTICLE. .A Masur-Levy P; Tavris DR; Elsey-Pica L. .I 275583 .U 91010394 .S J Am Diet Assoc 9101; 90(10):1429-31 .M Adolescence; Caloric Intake; Cardiovascular Diseases/*PC; Cholesterol, Dietary/*AD; Diet Records; Dietary Fats/*AD; Fatty Acids/*AD; Female; Human; Male; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Sources of fat, fatty acids, and cholesterol in the diets of adolescents. .P JOURNAL ARTICLE. .A Witschi JC; Capper AL; Ellison RC. .I 275584 .U 91010395 .S J Am Diet Assoc 9101; 90(10):1431-3 .M Comparative Study; Diet Records/*; Eating/*; Female; Human; Questionnaires. .T Comparison of a food frequency questionnaire and a 3-day diet record. .P JOURNAL ARTICLE. .A Bergman EA; Boyungs JC; Erickson ML. .I 275585 .U 91010397 .S J Am Diet Assoc 9101; 90(10):1435-6 .M Adult; Body Weight/*; Fasting/*ME; Human; Islam/*; Male; Regression Analysis; Uric Acid/*BL. .T Effects of Ramadan fasting on plasma uric acid and body weight in healthy men. .P JOURNAL ARTICLE. .A Nomani MZ; Hallak MH; Siddiqui IP. .I 275586 .U 91010398 .S J Am Diet Assoc 9101; 90(10):1437-41 .M Dietetics/*; Food Services/*; Human; Hunger/*; Nutrition Disorders/*; Nutritional Status; Societies/*; United States. .T Position of the American Dietetic Association: domestic hunger and inadequate access to food. .P JOURNAL ARTICLE. .A Hinton AW; Heimindinger J; Foerster SB. .I 275587 .U 91010399 .S J Am Diet Assoc 9101; 90(10):1442-5 .M Dietetics/*; Marketing of Health Services/*; Nutrition/*; Physicians/*; Societies; United States. .T President's page: Rx for change. .P JOURNAL ARTICLE. .A Wellman NS; Finn SC. .I 275588 .U 91010400 .S J Am Diet Assoc 9101; 90(10):1451 .M Awards and Prizes/*; Dietetics/*/HI; History of Medicine, 20th Cent.; Periodicals; United States. .T Margaret A. Lavery wins Huddleson Award. .P CURRENT BIOG-OBIT; HISTORICAL ARTICLE; JOURNAL ARTICLE. .I 275589 .U 91010401 .S J Am Geriatr Soc 9101; 38(9):1008-10 .M Aged; Aged, 80 and over; Anthropometry/*MT; Arm/*AH; Body Height/*; Female; Human; Leg/*AH; Male; Regression Analysis; Reproducibility of Results; Sex Factors. .T Measurement of height in the elderly [see comments] .P JOURNAL ARTICLE. .W Height is an essential variable when assessing renal clearance, nutritional status, and absorption. Standard methods of estimating height are impractical in the nonambulant. One hundred sixty-five elderly inpatients were studied. Total standing height, knee-to-floor height, and tibial length were measured. Total arm, upper arm, and forearm measurements were obtained in both erect and supine positions. Measured height correlated best with supine total arm length (R2 = .69), knee-to-floor height (R2 = .63), and erect forearm length (R2 = .61). A nomogram relating both supine total arm length and knee-to-floor height with the patient's measured height has been prepared. .A Haboubi NY; Hudson PR; Pathy MS. .I 275590 .U 91010402 .S J Am Geriatr Soc 9101; 38(9):1011-5 .M Age Factors; Aged; Aged, 80 and over; Cross-Sectional Studies; Decision Making; Documentation; Female; Hospitalization; Human; Length of Stay; Male; Medical Records/*SN; Nursing Care/CL; Patient Admission; Patient Participation; Resuscitation Orders/*; Sex Factors; Skilled Nursing Facilities/*; Support, Non-U.S. Gov't. .T Do-not-resuscitate orders in an extended-care study group. .P JOURNAL ARTICLE. .W We examined the charts of 911 nursing home patients in Hennepin County, Minnesota, to determine the prevalence of written do-not-resuscitate (DNR) orders. Information regarding demographic characteristics, and whether a surrogate decisionmaker was available and participated in the decision, was also collected. Twenty-seven percent of patients had DNR orders. Ninety percent of all patients had potentially available surrogate decisionmakers. However, for 31% of patients with DNR orders, there was no documentation of patient or surrogate participation in the DNR decision. Univariate analysis identified female sex; increased age, level of care (skilled versus intermediate), presence of a potential surrogate decisionmaker, and increasing length of time since nursing home admission as factors associated with presence of DNR orders. When a logistic regression model was used, increased age, increased length of time since nursing home admission, skilled versus intermediate level of care, and presence of a surrogate decisionmaker were independently associated with presence of DNR status. Several variables are independently associated with written DNR orders; their relationship to the factors physicians use in decision making requires further study. .A Meyers RM; Lurie N; Breitenbucher RB; Waring CJ. .I 275591 .U 91010403 .S J Am Geriatr Soc 9101; 38(9):1016-22 .M Aged; Bacteriuria/EP/ET/MI; Equipment and Supplies/*ST; Equipment Design; Equipment Failure; Evaluation Studies; Female; Human; Incidence; Prevalence; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Urinary Catheterization/AE; Urinary Incontinence/NU/*TH. .T An external urine collection device for incontinent women. Evaluation of long-term use. .P JOURNAL ARTICLE. .W Urinary incontinence is common in aged women, may precipitate nursing home admission, and may prompt use of a urine collection device, usually an indwelling urethral catheter. The safety and efficacy of a new external urine collection device for women that is affixed to the perineum by an adhesive developed for ostomy bags was evaluated. Applied to 26 aged women, 78% of 2,264 devices were leak-free for 24 hours and 49% for 48 hours. The incidence of new bacteriuria was less than half that found in our earlier studies of long-term urethral catheters in the same institution. Perineal erythema was infrequent and preexisting decubitus ulcers improved or did not change. Four patients were withdrawn, one each because of periurethral itching, diminished urine output, recurrent wetness, and fracture of the proximal femur associated with severe osteoporosis. This device may offer an alternative to urethral catheters for management of urinary incontinence but should not be used on women with urine retention and should be used with care on women with severe osteoporosis. Controlled trials must determine effects upon bacteriologic complications and health-care costs. .A Johnson DE; Muncie HL; O'Reilly JL; Warren JW. .I 275592 .U 91010404 .S J Am Geriatr Soc 9101; 38(9):1023-4 .M Activities of Daily Living/*; Aged; Homes for the Aged; Human; Lung Diseases/*RA; Nursing Homes; Radiography/*MT/ST; Wheelchairs/*. .T Lateral chest roentgenograms in debilitated nursing home residents. .P JOURNAL ARTICLE. .A Vergauwen C; Drinka PJ; Larson P; Langer E. .I 275593 .U 91010405 .S J Am Geriatr Soc 9101; 38(9):1025-6 .M Activities of Daily Living; Aged; Case Report; Dementia/*CO/PP/RA; Equipment and Supplies/*; Human; Male; Myoclonus/*CO/ET; Shoulder Fractures/*ET/RA; Wheelchairs/*. .T Bilateral fractures of the humeral head related to myoclonic jerks and use of a tray table for positioning. .P JOURNAL ARTICLE. .A Drinka P; Langer E; DeSmet A; Bartz-Bentz C. .I 275594 .U 91010406 .S J Am Geriatr Soc 9101; 38(9):1027-36 .M Aged; Aging/*IM; Endotoxins/IM/PH; Human; Macrophage Activation; Shock, Septic/IM/PP; Tumor Necrosis Factor/BI/*IM/PH. .T A proinflammatory mediator with potential relevance in aging. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .A Beutler B. .I 275595 .U 91010407 .S J Am Geriatr Soc 9101; 38(9):1037-8 .M Aged; Decision Making, Organizational; Emergency Medical Services/OG; Homes for the Aged/*; Human; Nursing Homes/*; Organizational Policy; Outcome and Process Assessment (Health Care)/*; Prognosis; Resuscitation/*ST; Resuscitation Orders; Support, Non-U.S. Gov't. .T Resuscitating the nursing home resident. Futility and pseudofutility. .P JOURNAL ARTICLE. .A Miles SH. .I 275596 .U 91010408 .S J Am Geriatr Soc 9101; 38(9):1039-40 .M Activities of Daily Living; Adult; Aging/*PX; Attitude to Health/*; Case Report; Human; Internal-External Control; Male; Multiple Trauma/PP/*PX; Physicians/*PX. .T On getting older and getting younger again. .P JOURNAL ARTICLE. .A Silverman D. .I 275597 .U 91010410 .S J Am Geriatr Soc 9101; 38(9):1049-50 .M Activities of Daily Living; Aged; Geriatrics/*; Human; Organizational Objectives; Organizational Policy; Rehabilitation/EC/MA/*ST; Societies, Medical/*OG; United States. .T Geriatric rehabilitation. AGS Public Policy Committee. .P JOURNAL ARTICLE. .I 275598 .U 91010413 .S J Am Geriatr Soc 9101; 38(9):1055-6 .M Aged; Health Services Accessibility/EC/*ST; Health Services Needs and Demand/*; Human; Medicare/EC; Rehabilitation/EC/*ST; Reimbursement Mechanisms/EC/ST; United States. .T Expanded access to rehabilitation services for older people. An urgent need. [editorial] .P EDITORIAL. .A Reed RL; Gerety MB; Winograd CH. .I 275599 .U 91010414 .S J Am Geriatr Soc 9101; 38(9):1057 .M Aged; Attitude to Death/*; Human; Nursing Homes/*OG; Organizational Policy/*; Resuscitation/*ST. .T CPR in nursing homes [letter; comment] .P COMMENT; LETTER. .A Murphy DJ. .I 275600 .U 91010415 .S J Am Geriatr Soc 9101; 38(9):1057 .M Aged; Human; Mass Screening/OG/*ST; Neoplasms/*PC; Organizational Objectives. .T To screen or not to screen? [letter; comment] .P COMMENT; LETTER. .A Carlson JE. .I 275601 .U 91010416 .S J Am Geriatr Soc 9101; 38(9):1057-9 .M Geriatrics/*; Human; Periodicals/*; Prejudice/*. .T What do citations mean? [letter; comment] .P COMMENT; LETTER. .A Dean W. .I 275602 .U 91010417 .S J Am Geriatr Soc 9101; 38(9):1059 .M Aged; Alzheimer's Disease/CI/*ET; Case Report; Female; Human; Male; Marriage/*; Organophosphorus Compounds/AE. .T Dementing disease in a married couple [letter] [see comments] .P LETTER. .A Kuale J. .I 275603 .U 91010418 .S J Am Geriatr Soc 9101; 38(9):1059-60 .M Activities of Daily Living/*; Age Factors; Health Care Rationing/*; Human; Quality of Life/*. .T "The trajectory of dying": commentary and response [letter; comment] .P COMMENT; LETTER. .A Rudberg MA; Sachs GA; Cassel CK. .I 275604 .U 91010419 .S J Am Geriatr Soc 9101; 38(9):967-72 .M Accidental Falls/SN; Activities of Daily Living/*; Aged; Aged, 80 and over; Bed Rest/*AE; Female; Geriatric Assessment; Human; Incidence; Intermediate Care Facilities/*; Male; Mortality; Prognosis; Retrospective Studies; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Survival Rate. .T Taking to bed. Rapid functional decline in an independently mobile older population living in an intermediate-care facility. .P JOURNAL ARTICLE. .W The objective of this study was to determine the incidence and selected clinical outcomes of taking to bed among a population of independently ambulating older individuals. It was designed as a retrospective case series and was conducted in the intermediate-care facility of a not-for-profit, teaching nursing home. Our study group was composed of individuals over 65 years of age who became bed bound. Thirty-six taking-to-bed episodes occurred in 36 individuals during one calendar year, giving an incidence of 13 per 1,000 resident-months (95% CI, 4 to 23 per 1,000). Twelve of the 36 died within 3 months, and 17 within 6 months, but almost all who survived regained ambulation. Survival was significantly shorter for the five without localizing symptoms (P less than .05). Orthopedic, neurologic, psychiatric, and iatrogenic conditions were most commonly identified as concurrent medical events. Almost half who took to bed had multiple concurrent medical events, and these residents were more likely to present without localizing symptoms (P less than .05). Twenty-one (58%) of the episodes occurred after a fall. The incidence of taking to bed in this population indicates that clinicians caring for older persons should be alert to its occurrence. The dramatic decline in mobility deserves careful assessment because it initiated a period of relatively rapid change in the health careers of the individuals we studied: almost half died within 6 months, but nearly all who survived regained ambulation. Those without localizing symptoms may have more complex interacting medical problems and a worse prognosis. .A Clark LP; Dion DM; Barker WH. .I 275605 .U 91010420 .S J Am Geriatr Soc 9101; 38(9):973-8 .M Activities of Daily Living; Aged; Aged, 80 and over; Alzheimer's Disease/CL/*PP; Bed Rest; Blood Pressure/*; Blood Pressure Monitors; Circadian Rhythm/*; Heart Rate; Human; Orientation. .T Absence of nocturnal fall in blood pressure in elderly persons with Alzheimer-type dementia. .P JOURNAL ARTICLE. .W Circadian changes of the blood pressure and heart rate in elderly normotensive bedridden patients with severe dementia of the Alzheimer type (group D) were compared with those in elderly normotensive bedridden patients without dementia (group R), normotensive subjects with normal daily activity (group N), and hypertensive patients with normal daily activity (group H). In groups R, N, and H, the blood pressure increased in the afternoon and decreased at midnight; in group D, however, although it increased in the afternoon, it did not decrease at night. The circadian changes of the heart rate were similar in all four groups, showing maxima in the afternoon and minima at midnight. Thus, a specific alteration was found in the circadian rhythm of the blood pressure in patients with Alzheimer-type dementia. .A Otsuka A; Mikami H; Katahira K; Nakamoto Y; Minamitani K; Imaoka M; Nishide M; Ogihara T. .I 275606 .U 91010421 .S J Am Geriatr Soc 9101; 38(9):979-84 .M Aged; Aged, 80 and over; Analgesics/*AD/TU; Depressive Disorder/DT; Drug Therapy/PX/*UT; Drug Therapy, Combination; Drugs, Non-Prescription/*AD/TU; Female; Human; Iowa; Male; Narcotics/AD/TU; Pain/DT/ET; Prevalence; Questionnaires; Self Administration; Self Medication/*; Support, U.S. Gov't, P.H.S.. .T Prevalence and characteristics of multiple analgesic drug use in an elderly study group. .P JOURNAL ARTICLE. .W With few exceptions, use of multiple analgesic drugs achieves dubious increases in analgesia while placing elders at increased risk of the many potential adverse effects of analgesic drugs. The potential for duplication of analgesic therapy among the elderly is great due to prevalent painful chronic conditions and the variety of prescription and nonprescription analgesic remedies available. The prevalence of multiple analgesic product use and patterns of concurrent use of different analgesic categories was investigated in a geographically defined population of persons 65 years of age and older. The demographic characteristics of users of multiple analgesic drug products were examined, as were their smoking status, alcohol use, lifetime history rates of major illnesses, physical functioning, pain experiences, memory performance, and depressive symptoms. A substantial proportion of analgesic users reported taking multiple products in the preceding 2 weeks (14.4% of female and 10.5% of male analgesic users). Men who reported pain in the preceding year were more likely to use multiple analgesic products. Women who experienced pain or limited physical functioning, or who had higher depressive symptom scores or a life-time history of ulcers were most likely to use multiple analgesic products. Thus, although some users of multiple analgesic products reported significant pain, several other factors were shown to be related to the phenomenon of multiple use. .A Chrischilles EA; Lemke JH; Wallace RB; Drube GA. .I 275607 .U 91010422 .S J Am Geriatr Soc 9101; 38(9):985-8 .M Activities of Daily Living; Aged; Anti-Inflammatory Agents, Non-Steroidal/*TU; Comparative Study; Consumer Satisfaction; Double-Blind Method; Endoscopy; Female; Human; Imidazoles/AD/AE/*TU; Male; Osteoarthritis/*DT/PP/PX; Peptic Ulcer/*CI/DI/PA; Piroxicam/AD/AE/*TU; Salicylates/AD/AE/*TU. .T Imidazole salicylate versus piroxicam in the treatment of arthrosis in elderly patients. A double-blind clinical and endoscopic trial. .P CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL. .W The clinical efficacy and gastroduodenal tolerability of imidazole salicylate (imidazole 2-hydroxybenzoate, ITF 182), a new synthetic drug with an anti-inflammatory action, was evaluated endoscopically in comparison with those of piroxicam in elderly patients suffering from osteoarthrosis. Of the 41 patients entering the trial, only 38 completed the protocol (6 men and 32 women; mean age, 71; range, 65-80 years). After upper gastrointestinal endoscopy for the purpose of excluding gastric and duodenal mucosal lesions, the patients were allocated at random, according to a double-blind, double-dummy protocol, to treatment either with imidazole salicylate 750 mg three times daily or with piroxicam 20 mg once daily for a period of 4 weeks. Imidazole salicylate proved active in controlling a number of the pain symptoms caused by arthrosis, although its efficacy was inferior to that of piroxicam. Grade 2 gastric mucosal lesions were detected in 1 of 20 patients (5%) treated with imidazole salicylate; lesions corresponding to grades 2, 3, and 4 were found in 6 of 18 (33%) of those treated with piroxicam (P = .034). Painful dyspepsia was reported by 15% of the patients in the imidazole salicylate group and by 28% of those in the piroxicam group. On the basis of these results and under the experimental conditions adopted in this trial, the authors concluded that imidazole salicylate is characterized by good gastric tolerability and can thus be used in the treatment of rheumatic diseases in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS) .A Montrone F; Petrillo M; Ardizzone S; Scaricabarozzi I; Scotti A; Caruso I; Bianchi Porro G. .I 275608 .U 91010423 .S J Am Geriatr Soc 9101; 38(9):989-92 .M Aged; Biopsy; Case Report; Diagnosis, Differential; Fever of Unknown Origin/*ET/PP; Giant Lymph Node Hyperplasia/*CO/DI/PA; Human; Male; Recurrence; Support, Non-U.S. Gov't. .T Fever of unknown origin in an elderly patient diagnosed at postmortem examination as multifocal angiofollicular lymph node hyperplasia. .P JOURNAL ARTICLE. .A Cutson TM; Lomasney JW; Schmader KE. .I 275609 .U 91010424 .S J Am Geriatr Soc 9101; 38(9):993-8 .M Activities of Daily Living/*; Aged; Aged, 80 and over; Cognition Disorders/CO/DI; Evaluation Studies; Female; Geriatric Assessment/*; Human; Male; Memory, Short-Term; Questionnaires/*ST; Reproducibility of Results; Support, U.S. Gov't, P.H.S.. .T Short-term variability of measures of physical function in older people. .P JOURNAL ARTICLE. .W Self reported physical function was assessed in telephone interviews approximately 3 weeks apart for a sample of 193 persons aged 69 or older. Three measures of physical function were used: a modified Activities of Daily Living scale, three items proposed by Rosow and Breslau, and five items from among those used by Nagi. Agreement between first and second interviews was very good; most subjects reported no impairment in function at either interview. Among those who reported some impairment, the degree of limitation within the specific activities reported as limited and the total number of activities with any degree of limitation agreed exactly for most and within one level for almost all subjects. There was no evidence to suggest that age or cognitive impairment affected the variability of the responses, and reported declines and improvements in function were about equally common. .A Smith LA; Branch LG; Scherr PA; Wetle T; Evans DA; Hebert L; Taylor JO. .I 275610 .U 91010425 .S J Am Geriatr Soc 9101; 38(9):999-1007 .M Aged; Aged, 80 and over; Alzheimer's Disease/DT/PP/*PX; Antidepressive Agents, Tricyclic/AE/TU; Cluster Analysis; Dementia, Vascular/DI/PP/*PX; Diet Surveys; Dietary Carbohydrates/*; Dietary Fats; Female; Food Preferences/*PX; Human; Male; Support, Non-U.S. Gov't. .T Dietary preference for sweet foods in patients with dementia [see comments] .P JOURNAL ARTICLE. .W Using a telephone survey, patients with probable Alzheimer's disease (n = 31) and vascular dementia (n = 14) were compared with elderly normal controls (n = 43) in preferences for different foods. Patients with Alzheimer's disease had a greater preference than normal controls for relatively high-fat, sweet foods and for high-sugar, low-fat foods, but did not significantly differ in preference for other foods, including those high in complex carbohydrates and protein. Vascular dementia patients showed a similar pattern, not significantly different from that for Alzheimer's patients. Results did not consistently support a hypothesis that increased sweet preference is a nonspecific form of disinhibited behavior related to declining mental status, nor was a hypothesis relating sweet preference to serotonin activity within the brain consistently supported. Results provide preliminary evidence that craving for sweet food may be a significant part of the clinical syndrome of dementia, but further research is needed to delineate the psychological and biological mechanisms accounting for it. .A Mungas D; Cooper JK; Weiler PG; Gietzen D; Franzi C; Bernick C. .I 275611 .U 91010537 .S J Clin Gastroenterol 9101; 12 Suppl 1:S1-192 .M Animal; Gastric Mucosa/*; Human; Stomach Diseases/*; Support, Non-U.S. Gov't. .T The Second Shimoda International Symposium on Gastroduodenal Mucosal Protection. Proceedings of a symposium. Shimoda, Shizuoka, Japan, November 24-25, 1988. .P MEETING REPORT; OVERALL. .I 275612 .U 91010538 .S J Clin Gastroenterol 9101; 12 Suppl 1:S1-7 .M Animal; Binding Sites; Burns/*ME; Gastric Mucosa/*ME; Glycoproteins/*ME; Lectins/ME; Male; Microscopy, Electron; Rats; Rats, Inbred Strains; Stomach Ulcer/*ME; Stress/*ME. .T Alternation of gastric mucosal glycoprotein (lectin-binding pattern) in gastric mucosa in stress. A light and electron microscopic study. .P JOURNAL ARTICLE. .W Gastric mucosal cells of the rat glandular stomach were studied by light and electron microscopic procedures by use of lectins in the development of acute gastric mucosal lesions. Effects of the H2-receptor antagonist sofalcone (2'carboxymethoxy-4,4'-bis 3-methyl-2) and truncal vagotomy with pyloroplasty on lectin binding sites and distribution were also investigated. Biotinylated lectins in combination with ABC (avidin-biotinyl peroxidase complex) method were used for light and horseradish peroxidase (HRP)-labeled lectins for electron microscopic studies. Gastric mucosal cells showed the specific binding pattern for each lectin by light microscopy. Especially, binding sites and distribution of peanut agglutinin (PNA) were characteristic after induction of stress, truncal vagotomy, and administration of each drug. Staining and distribution increased in the gastric mucosa upward and downward after that. In electron microscopic studies, PNA strongly stained the membranes of the intracellular secretory canaliculi of a parietal cell. These results suggested that alternation of binding sites and distribution was regulated by change of gastric mucosal blood flow and of acidity in the parietal cells. Therefore, increase of glycoconjugate distribution is supposed to be a possibility of cytoprotective effect for a change of environment in the parietal cells. .A Kitajima M; Mogi M; Kiuchi T; Shimizu A; Nakajima M; Oshima A; Kawakami H; Hirano H. .I 275613 .U 91010539 .S J Clin Gastroenterol 9101; 12 Suppl 1:S104-9 .M Ammonia/AE/*ME; Animal; Gastric Mucosa/DE/*PA; Helicobacter pylori/EN; Hydrolysis; Male; Rats; Rats, Inbred Strains; Stomach Ulcer/*ET; Urea/*ME; Urease/*ME. .T Generation of ammonia and mucosal lesion formation following hydrolysis of urea by urease in the rat stomach. .P JOURNAL ARTICLE. .W We examined the morphological changes in gastric mucosa and the generation of ammonia after exposure of the rat stomach to urea in the presence of urease, in attempts to investigate a pathophysiological role of urea, urease, and ammonia system in gastric ulcer diseases. Exposure of the stomach for 20 min to 2 ml urea (0.025-0.2%) together with urease (100 IU) induced histological damages in a concentration-related manner. Either urea or urease alone did not induce any histological change in the mucosa. Instillation of urea into the stomach generated ammonia in the presence of urease; the amount of ammonia was increased depending on the concentration of urea, and was closely associated with the severity of histological damage. The exposure of the stomach to ammonia (NH4OH: 0.01-0.1%) also produced histological damages in the gastric mucosa in a concentration-related manner. The characteristics of injury induced by 0.5-1.0% ammonia were stasis of microcirculation, disruption of the surface epithelial cells, and necrosis of the mucosa. These results demonstrated that ammonia generated from the hydrolysis of urea by urease in the stomach causes damages in the gastric mucosa. .A Murakami M; Yoo JK; Teramura S; Yamamoto K; Saita H; Matuo K; Asada T; Kita T. .I 275614 .U 91010540 .S J Clin Gastroenterol 9101; 12 Suppl 1:S110-5 .M Anion Exchange Resins; Biological Transport, Active; Cation Exchange Resins; Comparative Study; Female; Gastric Mucosa/ME; Human; Hydrogen-Ion Concentration; Intestinal Mucosa/ME; Male; Mucus/*ME/PH; Pyloric Antrum; Sodium/*ME; Support, Non-U.S. Gov't. .T The Na+/H+ exchange and H+ diffusion properties of human postmortem mucus: a comparison of gastric antral, gastric body, jejunal and ileal mucus. .P JOURNAL ARTICLE. .W The stomach and small intestine are areas of major electrolyte and solute transport. Mechanisms of transport in these areas have been widely studied and basic understanding is available. However, the mucus that lines the stomach and intestine is an important layer whose properties and functions in electrolyte and solute transport are not well understood. In this study we examined the Na+/H+ exchange of mucus from the stomach body and antrum, the jejunum, and the ileum. Mucus from the stomach body and antrum is a cation exchanger, a property that aids the net unidirectional flux of H+ ions from parietal cells to lumen. In the jejunum and ileum, mucus is an anion exchanger, which may be important in solute transport and absorption in the small bowel. In both the stomach and small bowel, proton movement is slow, which helps maintain the uphill pH gradient across gastric mucus and the downhill pH gradient across small intestinal mucus. .A Forlong C; Tasman-Jones C; Thomsen L; Clearwater J. .I 275615 .U 91010541 .S J Clin Gastroenterol 9101; 12 Suppl 1:S116-24 .M Animal; Dinoprostone/PD; DNA/*ME; Gastric Mucosa/DE/*ME; Indomethacin/PD; Male; Methylnitronitrosoguanidine/*PK; Mucus/DE/*PH; Pirenzepine/PD; Rats; Rats, Inbred Strains; Stomach Neoplasms/CI/PC. .T Effect of gastric mucus on the uptake of the carcinogen MNNG by gastric mucosal DNA. .P JOURNAL ARTICLE. .W In prostaglandin E2 (PGE2)-, pirenzepine-, and indomethacin-administered rats, the incorporation of N-[methyl-3H]-N'-nitro-N-nitrosoguanidine ([methyl-3H]MNNG) into gastric mucosal DNA was measured quantitatively by liquid scintillation counting after intragastric instillation of [methyl-3H]MNNG. The amount of incorporation was 25.4 +/- 5.9 pmol/mg DNA in control rats, 11.7 +/- 3.8 pmol/mg DNA in PGE2-administered rats, 6.2 +/- 5.6 pmol/mg DNA in pirenzepine-administered rats, and 42.9 +/- 14.4 pmol/mg DNA in indomethacin-administered rats. PGE2 and pirenzepine significantly decreased the incorporation as compared with the control group. In contrast, indomethacin increased the incorporation. In addition, gastric mucosa of these drug-treated rats was studied histochemically. PGE2 and pirenzepine increased secretion of gastric mucus whereas indomethacin decreased it. It is possible that gastric mucus has a protective effect not only against ulcerogenic agents but also against carcinogens. It is considered that gastric mucus plays an important role in the defense mechanism against carcinogenesis. .A Torii A; Kameda H; Kawamura T; Onizawa N; Nozawa H; Ariizumi M; Egawa K; Kondoh K. .I 275616 .U 91010542 .S J Clin Gastroenterol 9101; 12 Suppl 1:S125-30 .M Animal; Anti-Inflammatory Agents, Non-Steroidal/*AE; Aspirin/AE; Chromatography, High Pressure Liquid; Gastric Mucosa/CH/*DE; Indomethacin/AE; Male; Mucus/*CH/DE; Prostaglandins/*AN; Radioimmunoassay; Rats; Rats, Inbred Strains; Time Factors. .T Correlation of gastric mucous volume with levels of five prostaglandins after gastric mucosal injuries by NSAIDs. .P JOURNAL ARTICLE. .W After administration of NSAIDs (aspirin and indomethacin), chronological changes in gastric mucous volume were determined. These mucous volume changes were evaluated in relation to the development of gastric mucosal injuries. Furthermore, quantitative changes in five kinds of prostaglandins (PGs) in the gastric mucosa were measured after administration of NSAIDs. Gastric mucus volume was measured using a video image processor (VIP), and five kinds of PGs were fractionated by high-performance liquid chromatography (HPLC) and quantitatively determined by radioimmunoassay (RIA). We found that NSAIDs decrease the levels of five kinds of PGs to the same extent. Also, gastric mucous volume is decreased after administration of aspirin and increased after administration of indomethacin. Accordingly, it is possible that each NSAID has a different mechanism of producing the gastric mucosal injury and acts on gastric mucus in a different manner. There was no parallel in changes between gastric mucous volume and PG levels of the different PGs in the gastric mucosa after administration of NSAIDs. .A Asada S; Okumura Y; Matsumoto A; Hirata I; Ohshiba S. .I 275617 .U 91010543 .S J Clin Gastroenterol 9101; 12 Suppl 1:S131-4 .M Adult; Dyspepsia/MI; Female; Gastric Mucosa/CH; Gastritis/ME/*MI; Helicobacter pylori/*IP; Helicobacter Infections/*ME; Human; Leukotrienes B/AN/*PH; Male; Middle Age. .T Possible role of leukotrienes in gastritis associated with Campylobacter pylori. .P JOURNAL ARTICLE. .W This study was done to evaluate the role of leukotrienes (LTs) in gastritis associated with Campylobacter pylori. Biopsy specimens of gastric mucosa were obtained endoscopically from 18 patients with nonulcer dyspepsia for bacteriological and histological examination and extraction of LTs. There was correlation between the LTB4 level in the mucosa and the degree of gastritis evaluated histologically. The level was higher when infiltration of neutrophils in the gastric mucosa was more extensive. The LTB4 level in mucosa infected with C. pylori was higher than that in noninfected mucosa. These findings suggest that endogenous LTs may be related to the pathogenesis of gastritis associated with C. pylori. .A Fukuda T; Kimura S; Arakawa T; Kobayashi K. .I 275618 .U 91010544 .S J Clin Gastroenterol 9101; 12 Suppl 1:S135-8 .M Anti-Ulcer Agents/*PD; Antibiotics, Lactam/*PD; Antibiotics, Macrolide/*PD; Chalcone/AA/PD; Comparative Study; Helicobacter pylori/*DE; Metronidazole/*PD; Microbial Sensitivity Tests; Microscopy, Electron. .T The susceptibility of Campylobacter pylori to antiulcer agents and antibiotics. .P JOURNAL ARTICLE. .W The antibacterial activities of antiulcer agents and antibiotics against Campylobacter pylori were studied. The MIC90 values of three kinds of antibiotics--macrolides, beta-lactams, and metronidazole--were 0.05-0.78, 0.39-1.56, and 12.5 micrograms/ml, respectively. They were more active than antiulcer agents such as H2-blockers and cetraxate with MIC90 values of greater than or equal to 1,600 and greater than 1,600 micrograms/ml, respectively. Especially, clarithromycin, a new derivative of erythromycin, showed an MIC90 of 0.05 microgram/ml. However, the other antiulcer agents such as sofalcone and tripotassium dicitrate bismuthate (TDB) also had MIC90 values of 50 and 6.25 micrograms/ml, respectively. Clarithromycin, sofalcone, and TDB showed bactericidal activity against C. pylori CLO2. The bactericidal actions of these drugs could be observed under electron microscopy. .A Nagate T; Numata K; Hanada K; Kondo I. .I 275619 .U 91010545 .S J Clin Gastroenterol 9101; 12 Suppl 1:S139-47 .M Acetic Acids; Animal; Gastric Mucosa/*UL; Male; Microscopy, Electron; Rats; Rats, Inbred Strains; Stomach Ulcer/CI/*PA; Time Factors; Wound Healing/*. .T "Healed" experimental gastric ulcers remain histologically and ultrastructurally abnormal. .P JOURNAL ARTICLE. .W The present study was designed to assess histologic and ultrastructural features of gastric mucosa in the areas of grossly healed ulcers (acetic acid-induced gastric ulcers) in rats. The specific question we studied was whether the structure and cellular composition of the gastric mucosa in an area of grossly healed ulcer were fully restored. Eighty Sprague-Dawley rats underwent laparotomy; 100% acetic acid was applied to the lower gastric corpus serosa for 30 s and the abdomen was closed. The stomachs were reopened after 2 weeks or after 2, 3, or 4 months. Standardized gastric wall specimens from the area of grossly healed ulcers were obtained, processed, and evaluated by light microscopy and by transmission electron microscopy. The gastric mucosa of grossly healed ulcers demonstrated re-epithelialization at each study time but the mucosa beneath the surface epithelium displayed prominent histologic and ultrastructural abnormalities. Two different patterns of scar could be distinguished: (a) the mucosa in the area of healed ulcer was thinner (25-45% reduction vs. normal), with increased connective tissue and poor differentiation and/or degenerative changes in the glandular cells; or (b) the mucosa displayed ballooning dilatation of gastric glands, reduction in the microvascular network, and poor differentiation of glandular cells. We conclude that (i) the subepithelial mucosa of grossly healed gastric ulcer displays disorganized restoration of glandular and vascular structures and remains histologically and ultrastructurally abnormal; (ii) these abnormalities may interfere with oxygenation, nutrient supply, and with mucosal resistance and defense, and therefore could be the basis for ulcer recurrence. .A Tarnawski A; Hollander D; Krause WJ; Dabros W; Stachura J; Gergely H. .I 275620 .U 91010546 .S J Clin Gastroenterol 9101; 12 Suppl 1:S14-8 .M Animal; Bethanechol Compounds/PD; Bicarbonates/*ME; Dinoprostone/PD; Gastric Mucosa/DE/*SE; Guinea Pigs; Histamine/PD; Hydrogen-Ion Concentration; In Vitro; Male; Pyloric Antrum; 8-Bromo Cyclic Adenosine Monophosphate/PD. .T Bicarbonate secretion in isolated guinea pig antrum. .P JOURNAL ARTICLE. .W HCO3- secretion was investigated in isolated guinea pig antral mucosa mounted in Ussing chambers. The rate of HCO3- secretion was measured by a pH-stat system. The antral mucosa spontaneously secreted HCO3- at a rate of about 0.5 microEq cm-2 h-1. Bethanechol (100 microM) or 8-bromoadenosine 3':5'-cyclic monophosphate (8-Br-cAMP, 1 mM) induced a significant increase in HCO3- secretion. Prostaglandin E2 (1 microM) also produced an increase in HCO3- secretion, although it was less effective than either bethanechol or 8-Br-cAMP. Histamine (100 microM) did not affect HCO3- secretion. This preparation may be suited to the study of the precise mechanisms by which neurohumoral factors regulate gastric HCO3- secretion. .A Suzuki A; Kameyama J; Tsukamoto M; Suzuki Y. .I 275621 .U 91010547 .S J Clin Gastroenterol 9101; 12 Suppl 1:S148-57 .M Acetic Acids/*; Animal; Gastric Mucosa/BS/*DE; Granulation Tissue/UL; Male; Microcirculation/UL; Microscopy, Electron; Rats; Rats, Inbred Strains; Stomach Ulcer/*CI/PA; Time Factors; Vasodilation/DE. .T Vascular and microvascular changes--key factors in the development of acetic acid-induced gastric ulcers in rats. .P JOURNAL ARTICLE. .W The present study examined the time sequence and histologic and ultrastructural features of the formation and evolution of experimental, acetic acid-induced gastric ulcerations in rats. One hundred percent acetic acid was applied to the gastric serosa of 140 fasted male Sprague-Dawley rats through a polyethylene tube for 30 s. Gastric mucosal changes were evaluated at 1, 5, 15, and 30 min, 1 and 3 h, and 1, 2, 3, 5, 8, and 11 days after acetic acid application by visual inspection, by quantitative and qualitative light microscopy, and by transmission electron microscopy. Following exposure to acetic acid, the earliest morphologic changes occurred at 1 min and consisted of dilatation of large submucosal veins and arteries and mucosal collecting venules. Five to 15 minutes after injury, thrombi developed in submucosal veins and collecting venules, leading to microvascular stasis and mucosal necrosis. By 3 h, necrotic masses started to detach. By 24-48 h, necrotic changes penetrated the submucosa. By 72 h, most ulcers underwent transition into a "chronic" stage characterized histologically by the presence of granulation tissue at the bottom, and the appearance of a transitional healing zone at the margins. By 5 days, an increased amount of granulation tissue was observed and the gastric glands in transitional zones at the ulcer margin displayed cystic dilatation. Based on this study, we conclude that a key feature of acetic acid-induced ulcer formation is the early vascular and microvascular injury, which precedes glandular cell necrosis. .A Tarnawski A; Hollander D; Stachura J; Krause WJ; Eltorai M; Dabros W; Gergely H. .I 275622 .U 91010549 .S J Clin Gastroenterol 9101; 12 Suppl 1:S170-6 .M Alcohol, Ethyl/*TO; Animal; Blood Flow Velocity/DE; Gastric Mucosa/BS/*DE; Male; Microcirculation/DE; Prostaglandin D2/*TU; Rats; Rats, Inbred Strains; Regional Blood Flow/DE. .T Protective effect of PGD2 against ethanol-induced gastric mucosal injury in rats. .P JOURNAL ARTICLE. .W The protective effect of prostaglandin D2 (PGD2) in ethanol-, HCl-, or NaCl-induced gastric mucosal injury was investigated. To clarify the mechanism, the gastric mucosal hemodynamics were also investigated using reflectance spectrophotometry and laser Doppler flowmetry in anesthetized rats. PGD2 administered orally significantly reduced the ethanol-induced mucosal injury. Although it did not reach any significance, PGD2 also reduced 0.6 N HCl-induced mucosal damage, and slightly reduced 25% NaCl-induced mucosal damage. Topical application of PGD2 did not affect gastric mucosal hemodynamics at steady state before the administration of necrotizing agent. However, PGD2 significantly improved the gastric mucosal microcirculatory congestion caused by ethanol, and partly improved 0.6 N HCl-induced ischemia. However, it did not improve the 25% NaCl-induced mucosal congestion. The results indicated that PGD2 had a protective effect in the ethanol-induced gastric mucosal injury through the improvement of gastric mucosal microcirculation. However, further investigations are needed to clarify the precise effect of PGD2 in 0.6 N HCl- or 25% NaCl-induced mucosal damage. .A Kawano S; Sato N; Matsunaga T; Tsuji S; Ogihara T; Tanimura H; Nagano K; Kamada T. .I 275623 .U 91010550 .S J Clin Gastroenterol 9101; 12 Suppl 1:S177-80 .M Alcohol, Ethyl/PD; Animal; Anti-Ulcer Agents/*PD; Cells, Cultured; Chalcone/*AA/PD; Cimetidine/PD; Gastric Mucosa/*DE; In Vitro; Male; Microscopy, Electron, Scanning; Rats; Rats, Inbred Strains; 16,16-Dimethylprostaglandin E2/*PD. .T Protective effect of sofalcone and 16,16-dimethyl-PGE2 on isolated rat gastric cells. .P JOURNAL ARTICLE. .W The effects of 16,16-dimethylprostaglandin E2 (dm-PGE2) and sofalcone on damage caused by ethanol in surface epithelial cells isolated from rat stomach were examined. The surface epithelial cells (SECs) accounted for 83% of the isolated gastric mucosal cells, mucus neck cells for 5%, parietal cells for 9%, and chief cells for 3%. To suspensions of SEC, either dm-PGE2 at concentrations of 10(-7), 10(-6), or 10(-5) M or sofalcone at concentrations from 5 X 10(-6) to 10(-4) M was added; some cells were treated with neither drug. Ten minutes later, ethanol was added to each cell suspension to a final concentration of 15%, and 5 min later the viability was evaluated by trypan blue exclusion. At 10(-6) M, dm-PGE2 reduced ethanol-induced cell damage most strongly (p less than 0.001). Sofalcone also helped to prevent cell damage caused by ethanol in a dose-dependent manner. These results suggest that dm-PGE2 and sofalcone protect gastric mucosa not only from gross visible damage but they directly protect gastric cells from damage. .A Kobayashi K; Arakawa T; Nakamura A; Nakamura H. .I 275624 .U 91010551 .S J Clin Gastroenterol 9101; 12 Suppl 1:S181-6 .M Animal; Anti-Ulcer Agents/*TU; Autoradiography; Cell Division/DE; Chalcone/*AA/TU; Gastric Mucosa/*DE; Gastritis/CI/*DT; Male; Rats; Rats, Inbred Strains; Taurocholic Acid; Wound Healing/DE. .T Further study of mucosal repair by sofalcone in experimental gastritis. .P JOURNAL ARTICLE. .W The effect of sofalcone on the glandular structure and cell proliferation in the gastric mucosa of rats with gastritis induced by the administration of sodium taurocholate (TCA) for 6 months was examined by histoquantitative analysis and [3H]thymidine autoradiography. Morphometric observation revealed that, with TCA treatment, mucosal thickness, parietal cell mass, and the ratios of the length of the glandular portion/total length of the gastric gland were decreased in both the fundic and pyloric glands. Inflammatory cell infiltration and collagenous fiber proliferation were present in the gastric mucosa following TCA and indicated the presence of atrophic gastritis. These atrophic changes and inflammatory cell infiltration were reversed by a 3 week administration of sofalcone. Cellular proliferative activity assessed by the labeling indices of the gastric mucosa increased in TCA-induced gastritis in rats. The administration of sofalcone to rats with TCA-induced gastritis significantly increased labeling indices, particularly in the pyloric glands. From these results, it appears that sofalcone stimulates the compensatory increase in proliferative activity of generative cells, which then may become available to heal the gastritis. .A Kishimoto S; Kobuke K; Kobayashi H; Kajiyama G; Miyoshi A; Kohno Y; Tanikawa K; Ohta K; Suwa T. .I 275625 .U 91010552 .S J Clin Gastroenterol 9101; 12 Suppl 1:S187-91 .M Acetic Acids; Animal; Comparative Study; Drug Therapy, Combination; Epidermal Growth Factor-Urogastrone/*TU; Male; Omeprazole/*TU; Rats; Rats, Inbred Strains; Stomach Ulcer/CI/*DT; Sucralfate/*TU; Wound Healing/DE. .T Effect of epidermal growth factor in combination with sucralfate or omeprazole on the healing of chronic gastric ulcers in the rat. .P JOURNAL ARTICLE. .W Epidermal growth factor (EGF) has been shown to enhance healing of experimental gastric ulcers when given subcutaneously or orally in the drinking water. This effect of EGF occurs without reducing gastric acid secretion. On the other hand, EGF reportedly is excreted rapidly from gastric lumen when administered by intragastric bolus. This suggests that further stimulation of ulcer healing may be expected if EGF is given with an acid-suppressive agent or with an agent allowing EGF to remain in rat gastric lumen at high concentrations. In the present study, EGF administered by gastric intubation at a dose of 10 micrograms/kg, which is three times smaller than reported in previous studies, was evaluated for its effect on acetic acid-induced rat gastric ulcers in combination with sucralfate or omeprazole. Sucralfate is well known selectively to bind proteins covering the ulcer base, and omeprazole is a potent acid-suppressive agent. Prior to the study of combined EGF and sucralfate, oral sucralfate was confirmed to allow endogenous gastric EGF and mouse EGF given exogenously to remain at high concentrations in gastric contents and tissues. EGF and sucralfate (2 g/kg/day) given alone failed to stimulate ulcer healing in submandibularectomized rats (SMR rat) whose endogenous gastric EGF was depleted. However, the combination of both drugs administered at the same doses significantly accelerated ulcer healing in the SMR rat. Omeprazole (200 mg/kg/day) significantly enhanced ulcer healing regardless of removal of the submandibular glands. The combination of EGF and omeprazole further stimulated ulcer healing in the SMR rat.(ABSTRACT TRUNCATED AT 250 WORDS) .A Itoh M; Imai S; Joh T; Yokoyama Y; Yasue N; Iwai A; Matsusako K; Endoh K; Kawai T; Takeuchi T. .I 275626 .U 91010553 .S J Clin Gastroenterol 9101; 12 Suppl 1:S19-24 .M Animal; Bicarbonates/*ME; Duodenum/*DE; Female; Intestinal Mucosa/DE/*SE; Male; Nicotine/*PD; Rabbits; Rats; Rats, Inbred Strains; Smoke/*AE; Support, Non-U.S. Gov't; Time Factors; Tobacco/*. .T Effects of cigarette smoke and nicotine on duodenal bicarbonate secretion in the rabbit and the rat. .P JOURNAL ARTICLE. .W The effects of short-time exposure to cigarette smoke on duodenal mucosal bicarbonate secretion were studied in anesthetized rabbits and rats. The bicarbonate secretion was measured by continuous titration of recirculating luminal perfusate. In artificially ventilated rabbits, intermittent exposure to cigarette smoke during two 10-min periods caused a marked (approximately 40%) decrease (p less than 0.01) in duodenal bicarbonate secretion. After the exposures, secretion gradually recovered and had returned to the pre-exposure rate after 50 min. The decrease in secretion was associated with decreases in heart rate (approximately 15%) and blood pressure (approximately 30%) that, however, were of shorter duration. Neither reduced amounts of smoke (1/6 or 1/3) nor nicotine (25-1,000 micrograms/kg, intravenously) had any major effect on the bicarbonate secretion. In the spontaneously breathing rat, smoke was administered for 1-2 breaths every 30 s during a 5-min period. This exposure resulted in a significant (p less than 0.05) decrease in bicarbonate secretion and some increase in the blood pressure. Exposure to smoke had no effect on the secretion in rats with both splanchnic nerves cut, suggesting neural sympathetic mediation of the smoke-induced inhibition. .A Granstam SO; Jonson C; Fandriks L; Holm L; Flemstrom G. .I 275627 .U 91010554 .S J Clin Gastroenterol 9101; 12 Suppl 1:S25-31 .M Alcohol, Ethyl/*AE; Animal; Dinoprostone/*PH; Gastric Mucosa/BS/*DE; Male; Microcirculation/DE; Muscle, Smooth/DE/PH; Rats; Rats, Inbred Strains; Support, Non-U.S. Gov't; SRS-A/*PH. .T Possible role of endogenous prostaglandins against ethanol injury in rat stomach. .P JOURNAL ARTICLE. .W Exposure of the gastric mucosa for 3 min to 30% intragastric ethanol induced mucosal injury that appeared dark red in anesthetized rats. Microscopic observation of the microvasculature in the injured area after exsanguination of rats and in living rats confirmed that there was congestion of the blood flow in the collecting venules and capillaries. Hemorrhage was observed about 30 min after application of ethanol. Monastral blue dye was deposited along the postcapillary venules only at the border of the congestion area. A selective 5-lipoxygenase inhibitor, AA-861, inhibited the gastric lesion, and immunoreactive leukotriene C4 (LTC4) was detected in the gastric wall. Previous exposure of the gastric mucosa to 1.0 M NaCl solution inhibited the ethanol-induced mucosal injury markedly. NaCl solutions (0.5-1.0 M) also suppressed the electrical activity of smooth muscle and the suppression was released by indomethacin. Having observed that PGE2 generation in the stomach was induced dose-dependently by intragastric NaCl solutions (0.5-1.0 M), we propose the hypothesis that peptide LTs released by intragastric ethanol constrict the collecting venules or lamina muscularis mucosae and induce congestion of these venules, whereas the PGE2 released by intragastric NaCl solution releases the congestion of the collecting venules directly or through suppression of contraction of the lamina muscularis. .A Katori M; Nishiyama K; Ueno A; Suzuki Y. .I 275628 .U 91010555 .S J Clin Gastroenterol 9101; 12 Suppl 1:S32-8 .M Alcohol, Ethyl/AE; Animal; Dinoprostone/BI; Gastric Mucosa/CY/*PH; Heat/AE; Indomethacin/PD; Male; Rats; Rats, Inbred Strains. .T In vitro adaptive cytoprotection in gastric cells isolated from rat stomach. .P JOURNAL ARTICLE. .W The effects of mild irritants (2-5% ethanol or water at 45-55 degrees C) on production of prostaglandins (PGs) in gastric cells isolated from rat stomach and the damage caused by 15% ethanol were assessed. Gastric cells were isolated by the method of Matuoka et al., by which a suspension rich in surface epithelial cells was obtained. Synthesis of PGE2 by the cells was stimulated by 3% ethanol or water at 50 degrees C. The damage caused by 15% ethanol was much less in the cells treated with 3% ethanol or 50 degrees C water beforehand than in untreated cells. This protective effect by 3% ethanol or 50 degrees C water was abolished when the cells were treated with 10(-4) M indomethacin. These results suggest that 3% ethanol or 50 degrees C water protects the gastric cells from damage caused by 15% ethanol, possibly via endogenous PGs. .A Arakawa T; Nakamura A; Fukuda T; Higuchi K; Nakamura H; Kobayashi K. .I 275629 .U 91010557 .S J Clin Gastroenterol 9101; 12 Suppl 1:S48-51 .M Adrenal Glands/*PH; Adrenalectomy; Animal; Cold/AE; Comparative Study; Dinoprostone/*ME; Gastric Mucosa/*ME; Male; Rats; Rats, Inbred Lew; Restraint, Physical; Stress/*PP; 6-Ketoprostaglandin F1 alpha/*ME. .T Effects of stress on gastric mucosal prostaglandin generation in intact, adrenalectomized, and sham-operated rats. .P JOURNAL ARTICLE. .W To study the effects of (a) cold restraint stress and (b) adrenalectomy in association with cold restraint stress on gastric mucosal ulceration and prostaglandin generation, we performed two experiments. In the first, 40 rats were divided into four groups of 10 rats each: (a) unstressed and (b) stressed for 0.5 h, (c) stressed for 2 h, and (d) stressed for 4 h. In the second experiment, another 80 rats were divided into four groups of 20 rats each: (a) adrenalectomy plus cold restraint stress for 2 h, (b) adrenalectomy plus no stress, (c) sham operated plus 2 h of stress, and (d) sham operated plus no stress. In both experiments we recorded an ulcer index and measured mucosal generation of prostaglandin E2 (PGE2) and prostaglandin I2 (6-keto-PGF1a). In conclusion: (a) Cold restraint stress is associated with a time-dependent decrease in gastric mucosal PGE2 generation, but no change in 6-keto-PGF1a generation, and an increase in mucosal injury that is maximal by 2 h. (b) Adrenalectomy augments the effects of stress on mucosal injury but has no effect on prostaglandin generation; thus, the ulcerogenic effect of adrenalectomy appears to be independent of an effect on prostaglandin generation. .A Avunduk C; Eastwood GL; Polakowski N; Quimby GF. .I 275630 .U 91010558 .S J Clin Gastroenterol 9101; 12 Suppl 1:S52-7 .M Animal; Chromatography, Thin Layer; Comparative Study; Female; Gangliosides/AN; Gastric Mucosa/*CH/PH; Glycosphingolipids/*AN; Human; Male; Rabbits; Rats; Species Specificity; Sulfatides/AN/*ME. .T Glycosphingolipid composition of the gastric mucosa. A role of sulfatides in gastrointestinal mucosal defense? .P JOURNAL ARTICLE. .W The glycosphingolipid (GSL) compositions of the human, rabbit, and rat gastric mucosa were studied and compared. In neutral GSLs, although GalCer was the most abundant component in every tissue examined, species-specific differences were clearly observed in their composition. Acidic GSLs were composed of sulfatides and gangliosides. Every gastric mucosa contained sulfatides (GalCer-sulfate) in a high concentration. The concentrations of sulfatides per gram of dry weight were 416.0, 933.8, 394.0, 365.9, and 135.9 nmol for the human fundus, human antrum, rabbit fundus, rabbit antrum, and rat glandular stomach, respectively. On the other hand, gangliosides were less in these tissues. The molar ratios of sulfatides to GM3, a major ganglioside, were 4.3, 6.7, 11.1, 2.1, and 1.2 for each gastric mucosa described above, respectively. A high sulfatide concentration in animal gastric mucosa, with its structural similarity to sucralfate, implies that sulfatides may play an important role for gastrointestinal mucosal protection. .A Natomi H; Sugano K; Takaku F; Iwamori M. .I 275631 .U 91010560 .S J Clin Gastroenterol 9101; 12 Suppl 1:S65-71 .M Allopurinol/TU; Animal; Burns/*PA; Compound 48-80/PD; Female; Free Radical Scavengers; Free Radicals/*; Gastric Mucosa/*PA; Hyperthermia, Induced; Lipid Peroxidation; Male; Oxygen/*TO; Platelet Activating Factor/PD; Rats; Reperfusion Injury/CO; Shock, Traumatic/*PA. .T Role of oxygen-derived free radicals in the pathogenesis of gastric mucosal lesions in rats. .P JOURNAL ARTICLE. .W The role of oxygen-derived free radicals and lipid peroxidation in the pathogenesis of acute gastric mucosal erosion was investigated in rat models produced by burn shock stress, by treatment with regional hyperthermia, platelet activating factor, and compound 48/80, and by ischemia-reperfusion. In all experimental models, the increase in the gastric erosions and in TBA reactants in the gastric mucosa were significantly inhibited by the treatment with superoxide dismutase (SOD) and/or catalase. Pretreatment with allopurinol, a competitive inhibitor of xanthine oxidase, prevented considerably the gastric injury (a) induced by burn shock, (b) produced by treatment with compound 48/80, and (c) caused by ischemia-reperfusion. By the treatment with anti-rat neutrophil antibody, the gastric mucosal injuries induced by regional hyperthermia, platelet activating factor, and compound 48/80 were significantly inhibited; however, burn shock and ischemia-reperfusion injuries were not inhibited. These results suggest that oxygen-free radical and lipid peroxidation contribute to the formation of gastric mucosal lesions, and that the sources of oxygen radicals seem to be different among these experimental models. .A Yoshikawa T; Naito Y; Ueda S; Oyamada H; Takemura T; Yoshida N; Sugino S; Kondo M. .I 275632 .U 91010561 .S J Clin Gastroenterol 9101; 12 Suppl 1:S72-5 .M Animal; Autoradiography; Cell Division/DE; Comparative Study; Gastric Fundus; Gastric Mucosa/CY/*DE; Indomethacin/*PD; Male; Pyloric Antrum; Rats; Rats, Inbred Strains. .T Effects of single parenteral indomethacin injection in rat fundic and antral epithelial proliferation. .P JOURNAL ARTICLE. .W To study the effects of a single parenteral dose of indomethacin on gastric epithelial proliferation, we performed the following study. Male Wistar rats weighing about 200 g were divided into two groups and given single intraperitoneal injections of indomethacin 5 mg/kg, either suspended in 0.5% carboxymethyl cellulose sodium salt or vehicle alone, after an overnight fast. After 6 h, all rats were injected by tail vein with tritiated thymidine, 1 microCi/g body weight, to label proliferating cells and were killed 1 h later. Sections from fundic and antral mucosae were processed for light autoradiography. Parenteral indomethacin resulted in spotty erosions in fundic mucosa. Histologically, there was congestion with or without epithelial disruption. These areas were excluded in the proliferation measurements. There was a significant decrease not only in the number of labeled cells but also in the thickness of the proliferative zone with the thinning of the entire mucosal thickness in the fundic mucosa. None of the measurements in antral mucosa showed significant difference. These results showed that a single parenteral injection of indomethacin inhibits epithelial proliferation and decreases mucosal thickness in fundic, but not antral mucosa of the rat. .A Kuwayama H; Nakajima N; Matsuo Y; Eastwood GL. .I 275633 .U 91010562 .S J Clin Gastroenterol 9101; 12 Suppl 1:S76-84 .M Animal; Capillary Permeability/DE; Deoxyglucose/*PD; Evans Blue/PK; Gastric Mucosa/*DE; Gastrointestinal Motility/*DE; Indomethacin/*PD; Male; Rats; Rats, Inbred Strains. .T Increased microvascular permeability and lesion formation during gastric hypermotility caused by indomethacin and 2-deoxy-D-glucose in the rat. .P JOURNAL ARTICLE. .W The relationship between lesion formation, gastric motility, and vascular permeability was examined in rats using indomethacin and 2-deoxy-D-glucose (2DG). Both indomethacin (25 mg/kg s.c.) and 2DG (100 mg/kg/h i.v.) produced gastric hypermotility and induced lesions, mostly confined to the rugal crests of the mucosal folds; the onset of hypermotility preceded appearance of the lesions in both cases. The mucosal microvascular permeability as determined by the amount of extravasated dye (Evans blue) was increased in response to these two agents, and the permeability responses also preceded appearance of the lesions. Both the increased vascular permeability and the severity of lesions were significantly reduced when the hypermotility was inhibited by pretreatment with atropine (3 mg/kg s.c.). The severity of the lesions were also markedly reduced or worsened, respectively, by hydrocortisone (10 mg/kg s.c.) or N-ethylmaleimide (10 mg/kg s.c.) at the doses that significantly decreased or enhanced the vascular permeability responses caused by indomethacin and 2DG. These results suggest that the enhanced gastric motility as induced by indomethacin and 2DG may cause microcirculatory disturbances in the specific sites of the mucosa (mucosal folds), probably by abnormal compression of the gastric wall, leading to the increased microvascular permeability and cellular damage. .A Takeuchi K; Okada M; Ebara S; Osano H. .I 275634 .U 91010563 .S J Clin Gastroenterol 9101; 12 Suppl 1:S8-13 .M Alcohol, Ethyl; Animal; Antibodies, Monoclonal/DU; Blotting, Western; Fibronectins/*AN/IM; Gastric Mucosa/*CH; Human; Male; Rats; Rats, Inbred Strains; Stomach Ulcer/CI/ME. .T Fibronectin-related substance located in the chief cells of human and rat gastric mucosa. .P JOURNAL ARTICLE. .W A novel substance located in the chief cells of human and rat gastric mucosa, which was detected immunologically by either polyclonal or monoclonal antihuman fibronectin (FN) antibodies, is reported. All three polyclonal antihuman FN antibodies used in this study reacted immunohistologically exclusively with the chief cells. Monoclonal antibody against C-terminal peptide or cell binding peptide reacted clearly with the human chief cells, but monoclonal antibodies against FN N-terminal and midmolecule failed to react with the cells. Western blot analysis of the rat gastric mucosal extract with polyclonal antihuman FN antibody showed that this substance has a molecular weight of about 70,000 Da. Therefore, this substance appears to be a fragment containing the C-terminal peptide of whole molecule FN and thus in the present study is named FN-related substance (FNRS). In a further study with ethanol-induced ulcer model of the rat, the physiological significance of FNRS was examined. The FNRS decreased remarkably, in a dose-dependent manner, in the fundic mucosa of the rats that ingested ethanol. The FNRS appeared to be associated with development of mucosal damage and repair, subsequently playing, in part, an important role in the gastric mucosal protection mechanism. .A Maeda S; Yabana T; Ichiyanagi S; Chen J; Yachi A. .I 275635 .U 91010564 .S J Clin Gastroenterol 9101; 12 Suppl 1:S85-91 .M Alcohol, Ethyl/*TO; Animal; Arachidonate 5-Lipoxygenase/AI; Benzoquinones/PD; Gastric Mucosa/*BS/DE; Indomethacin/PD; Leukotrienes/*PH; Male; Microcirculation/DE; Premedication; Prostaglandins/*PH; Rats; Rats, Inbred Strains. .T Mucosal blood flow stasis and hypoxemia as the pathogenesis of acute gastric mucosal injury: role of endogenous leukotrienes and prostaglandins. .P JOURNAL ARTICLE. .W To clarify the roles of endogenous leukotrienes and prostaglandins in the ethanol-induced gastric mucosal injury, the effect of AA-861 (a selective 5-lipoxygenase inhibitor) and indomethacin (a cyclooxygenase inhibitor) on the ethanol-induced gastric mucosal lesions was investigated in fasted rats. Furthermore, the effect of these agents on the gastric mucosal microcirculatory disturbance induced by ethanol was also investigated using laser Doppler velocimetry and reflectance spectrophotometry. Forty percent ethanol caused mucosal microcirculatory stasis and mucosal hypoxemia, followed by mucosal injury. The pretreatment with AA-861 reduced the mucosal injury and significantly reduced the mucosal congestion and hypoxia induced by 40% ethanol. The pretreatment with indomethacin did not reduce the gastric mucosal damage or influence the mucosal blood flow stasis and the mucosal hypoxemia induced by ethanol. These results suggested that the increase of endogenous leukotrienes after intragastric administration of ethanol is responsible for the mucosal microcirculatory disturbance and mucosal tissue hypoxemia resulting in the mucosal injury, and that the decrease of prostaglandins alone may not play an important role in ethanol-induced mucosal injury. .A Tsuji S; Kawano S; Sato N; Kamada T. .I 275636 .U 91010565 .S J Clin Gastroenterol 9101; 12 Suppl 1:S92-8 .M Gastric Mucosa/*MI/UL; Gastritis/*MI; Helicobacter pylori/*IP; Helicobacter Infections/*MI; Human; Microscopy, Electron; Stomach Ulcer/*MI. .T Evidence for gastric mucosal cell invasion by C. pylori: an ultrastructural study. .P JOURNAL ARTICLE. .W It is now generally accepted that Campylobacter pylori is closely associated with peptic ulcer disease and chronic type B gastritis. Whether C. pylori is the direct etiologic cause of either or both of these illnesses remains unclear. Possible pathophysiologic effects of C. pylori are still a matter of debate and conjecture. Utilizing a small group of patients with gastric ulcers and chronic gastritis, we examined the ultrastructural relationship between C. pylori and gastric cells. Forty-eight percent of our gastric ulcer patients and 57% of our chronic gastritis patients had C. pylori in their lower corpus mucosa. Examination with the transmission electron microscope indicated a very close proximation by C. pylori to the surface epithelial cells strongly suggesting adherence. We also describe for the first time the invasion of gastric cells by C. pylori. Although an uncommon occurrence, we had repeated observations of C. pylori invading surface epithelial cells, parietal cells, and chief cells. Most of the intracellular C. pylori were intact but other forms appearing to be degenerating organisms were also seen. We suggest that cell invasion may be one mechanism by which C. pylori causes pathologic changes in the gastric mucosa. These observations may also explain why C. pylori chronically infects gastric cells and frequently recurs after treatment. .A Wyle FA; Tarnawski A; Schulman D; Dabros W. .I 275637 .U 91010566 .S J Clin Gastroenterol 9101; 12 Suppl 1:S99-103 .M Bacterial Adhesion; Campylobacter jejuni/PY; Cell Line; Cell Survival; Comparative Study; Escherichia coli/PY; Helicobacter pylori/*PY; Human; In Vitro; Microscopy, Electron; Stomach Neoplasms/*PA; Tumor Cells, Cultured/MI. .T Campylobacter pylori interactions with gastric cell tissue culture. .P JOURNAL ARTICLE. .W Many investigators have reported that gastric mucosal biopsies of patients with chronic gastritis and peptic ulcer disease show the presence of Campylobacter pylori in a large majority of cases. Histologic examinations of such tissues indicate a close approximation of C. pylori with gastric surface epithelial cells. A recent report has described both adherence and cell invasion of gastric cells by C. pylori. Using a transmission electron microscope, we have examined the interaction between C. pylori, C. jejuni, and E. coli in vitro with a gastric cancer cell line, Kato III. Our results indicate marked toxicity of E. coli and moderate toxicity of C. jejuni for Kato III cells. C. pylori had only a minor effect on tissue culture viability. C. pylori was found to have a strong association with the Kato III cell membranes and evidence of occasional cell invasion. Both C. jejuni and E. coli showed no attachment or association with the Kato III cells. We interpret these findings as indicating that C. pylori may have a specific adhesion for gastric cells. .A Wyle FA; Tarnawski A; Dabros W; Gergely H. .I 275638 .U 91010567 .S J Emerg Med 9101; 8(4):407-12 .M Activities of Daily Living; Aged; Comparative Study; Female; Heart Arrest/PX/*TH; Human; Male; Mental Processes; Middle Age; Myocardial Infarction/PX/TH; Neuropsychological Tests; Quality of Life/*; Resuscitation/*PX; Retrospective Studies. .T Neuropsychological outcome of survivors of out-of-hospital cardiac arrest. .P JOURNAL ARTICLE. .W Thirty patients resuscitated from out-of-hospital cardiac arrest (15 with and 15 without postanoxic coma on admission) underwent a clinical examination and neuropsychological testing. In order to assess quality of life, they were compared to two matched control groups; 15 patients with previous myocardial infarction and 15 healthy subjects. None of the survivors showed severe neurologic impairment, and all had returned to self-sufficient physical activity. However, the behavior rating scale scores were significantly worse in patients with postanoxic coma. The processing ability linked to memory was significantly worse in the postanoxic coma group. Mood disorders were also observed in this group, but they did not have pathological significance. The remarkably low incidence of neurologic and psychological sequelae in these resuscitated patients, particularly in those with early clinical evidence of severe cerebral damage, is an encouraging result that supports the therapeutic systems development and efforts in the management of out-of-hospital cardiac arrest. .A Bertini G; Giglioli C; Giovannini F; Bartoletti A; Cricelli F; Margheri M; Russo L; Taddei T; Taiti A. .I 275639 .U 91010568 .S J Emerg Med 9101; 8(4):413-7 .M Audio-Visual Aids/*; Child; Clinical Protocols/*; Emergency Medicine/MT; Emergency Service, Hospital/MA; Hospital Records; Hospitals, Rural/*; Human; Queensland; Reference Values; Wounds and Injuries/*TH. .T An aid to the management of pediatric trauma in peripheral centers--a proposal for a pediatric trauma board. .P JOURNAL ARTICLE. .W In 1986, 630,000 children under the age of 15 were living in Queensland. This accounted for 17% of Australia's pediatric population. That year there were 39 pediatric deaths in Queensland resulting from road traffic incidents. Another 408 injured children were admitted to hospital. Less than 20% of these children were treated in an accident and emergency (A&E) department staffed by a qualified pediatrician. Only 35% of the A&E departments were staffed by a qualified emergency physician. A Pediatric Trauma Board is proposed, which will lead to improvement in the care of injured or critically ill pediatric patients. This board is made of pre-marked whiteboard and includes normal pediatric values and replacement fluid flow charts; it is approximately three feet in height and six feet in width. The Board is aimed primarily at nonpediatric clinicians who may or may not be specifically trained or interested in emergency medicine. It provides quick, easy access to the normal values of vital signs for children of different ages and sizes. It enables accurate calculation of the fluid requirements for resuscitation and provides a means for following the response to this therapy. Drug doses per weight are provided. A copy of the board can be made on size A4 photostats for inclusion in the hospital chart as part of the admission notes. .A Sinnott MJ. .I 275640 .U 91010569 .S J Emerg Med 9101; 8(4):419-21 .M Abdominal Injuries/*ET/TH; Case Report; Child; Human; Male; Scrotum/*IN; Skating/*IN; Wounds, Penetrating/*ET/TH. .T Scroto-abdominal impalement injury in a skateboard rider. .P JOURNAL ARTICLE. .W The injuries sustained by skateboard riders vary from minor cuts and abrasions to fractures. This report describes a unique injury sustained by a young skateboard rider who was impaled on a metal rod. Literature review of over 1,254 skateboard injuries did not reveal any other instances of penetrating abdominal trauma. .A Carragher AM; Sulaiman SK; Panesar KJ. .I 275641 .U 91010571 .S J Emerg Med 9101; 8(4):429-31 .M Adolescence; Aneurysm, Dissecting/*RA/SU; Aorta, Thoracic/*IN; Aortic Rupture/*RA/SU; Aortography; Case Report; Human; Male. .T Traumatic rupture of the thoracic aorta presenting as transient paraplegia. .P JOURNAL ARTICLE. .W A patient involved in a high-speed motor vehicle accident presented paraplegic to the emergency department. He was noted to have an abnormal chest x-ray and, subsequently, underwent aortography which revealed aortic transection. The patient's paraplegia resolved spontaneously prior to definitive aortic repair hours later. Aortic rupture presenting as paraplegia is a rare association, but one an emergency physician should be cognizant of, especially in the case of blunt or decelerating trauma. .A Eaves CC. .I 275642 .U 91010572 .S J Emerg Med 9101; 8(4):433-5 .M Case Report; Child; Female; Firearms; Foreign Bodies/RA; Head Injuries/*ET/RA/SU; Human; Skull/RA; Tomography, X-Ray Computed; Wounds, Gunshot/*RA/SU. .T Pneumatic firearm injuries: trivial trauma or perilous pitfalls? .P JOURNAL ARTICLE. .W This report describes an injury due to a pneumatic firearm. Though powder firearm injuries are generally considered serious, pneumatic weapon injuries are often viewed as minor or insignificant trauma. Children and adolescents primarily wield these weapons contributing to their "harmless" aura. However, dramatic increases in muzzle and impact velocities have transformed the newer generation of pneumatic firearms into formidable weapons. Consequently, the literature is replete with increasing incidences of serious injury due to pneumatic weapons. .A Lucas RM; Mitterer D. .I 275643 .U 91010573 .S J Emerg Med 9101; 8(4):437-40 .M Case Report; Hand Injuries/*CO; Human; Male; Middle Age; Pasteurella/IP; Pasteurella Infections/*; Septicemia/ET/*MI; Wounds, Penetrating/*CO. .T A case of unexpected pasteurella multocida bacteremia. .P JOURNAL ARTICLE. .W A case of Pasteurella multocida bacteremia in a previously healthy hospital employee is presented. The patient had sustained a scratch from his dog four days prior to being seen in the emergency department with adequate healing and no evidence of localized infection. He presented with an acute febrile illness, and was discharged from the emergency department with a diagnosis of viral syndrome. He was asked to return to the hospital the next day when a bacteriology report of gram negative rods in both aerobic and anaerobic blood culture bottles was received in the emergency department. Pasteurella multocida bacteremia/septicemia is seen most frequently in immunocompromised patients but the diagnosis should be considered in any patient with a febrile illness and exposure to cats or dogs. .A Ernst AA; Sanders WM. .I 275644 .U 91010574 .S J Emerg Med 9101; 8(4):441-7 .M Adnexitis/PP; Adult; Appendicitis/PP; Case Report; Clinical Protocols; Female; Human; Male; Ovarian Cysts/DI/PP; Ovarian Diseases/PP; Pain/*ET/PP; Pelvis/AH/*IR; Peritonitis/PP; Torsion. .T Pelvic pain: lessons from anatomy and physiology. .P JOURNAL ARTICLE. .W Pelvic pain is often a difficult differential diagnosis in the emergency department. For physiologic reasons, pain in the pelvis is difficult to localize to a specific organ, and pelvic peritonitis is hard to recognize. On the other hand, differences in types of pain can be very useful in arriving at a correct diagnosis. The clinician must learn to recognize superficial and deep somatic pain, and differentiate between various types of visceral pain which originate from inflammation, ischemia, or colic. A review of the anatomy and physiology of pelvic pain helps identify some of the problems as well as potential aids in approaching the patient with pelvic pain. .A Abbott J. .I 275645 .U 91010575 .S J Emerg Med 9101; 8(4):449-50 .M Case Report; Charcoal/*TU; Epilepsy/DT; Human; Infant, Newborn; Male; Medication Errors; Phenobarbital/*PO/TU; Poisoning/TH; Sorbitol/AD. .T Treatment of phenobarbital poisoning with multiple dose activated charcoal in an infant. .P JOURNAL ARTICLE. .W A 28-day-old infant developed lethargy, hypotonia, and hypothermia following a phenobarbital overdose secondary to a pharmacist's error. He was treated with multiple dose activated charcoal (MDAC) and alkalinization of the urine, which resulted in prompt recovery with rapid elimination of the drug (t1/2-11.2 hours, expected 45 to 118 hours). The use of MDAC in this newborn was safe and effective. We suggest that age should not pose a barrier to the use of MDAC, when indicated. .A Amitai Y; Degani Y. .I 275646 .U 91010576 .S J Emerg Med 9101; 8(4):451-4 .M Adolescence; Adult; Aged; Algorithms; Antidepressive Agents, Tricyclic/*PO; Cost Control; Female; Hospitals, Community; Human; Length of Stay; Male; Middle Age; Patient Care Planning; Poisoning/EC/TH. .T Tricyclic antidepressant overdose: conservative management in a community hospital with cost-saving implications. .P JOURNAL ARTICLE. .W Reports of late-onset cardiovascular complications following tricyclic antidepressant (TCA) overdose have led to a very conservative approach to these patients. Many patients have been hospitalized for continuous cardiac monitoring, regardless of the clinical presentation. Management algorithms based on clinical predictors of outcome have recently been proposed. We used the algorithm developed by Tokarski and Young to retrospectively evaluate the care of 33 TCA overdose patients admitted to our hospital over a 3-year period. We then identified 11 patients who could have been treated on an outpatient basis had the algorithm been employed. Ten were admitted to a monitored unit and spent a mean of 31.6 +/- 15.64 hours on the unit. None of the 11 patients developed complications during their hospital stay. Use of the algorithm would have resulted in an estimated cost savings of 13 hospital days and $14,000. .A Banahan BF Jr; Schelkun PH. .I 275647 .U 91010577 .S J Emerg Med 9101; 8(4):455-61 .M Adult; Alcohol Dehydrogenase/AI; Alcohol, Methyl/ME/PO; Dose-Response Relationship, Drug; Double-Blind Method; Ethylene Glycols/ME/PO; Human; Male; Poisoning/DT; Pyrazoles/AD/*AE/TU; Support, U.S. Gov't, P.H.S.. .T Effects of 4-methylpyrazole, methanol/ethylene glycol antidote, in healthy humans. .P JOURNAL ARTICLE. .W 4-Methylpyrazole (4-MP), an inhibitor of alcohol dehydrogenase, may be useful for the treatment of methanol and ethylene glycol intoxications. A placebo-controlled, double blind, multiple dose, sequential, ascending-dose study has been performed to determine the tolerance of 4-MP in healthy volunteers. Oral loading doses of 4-MP were followed by supplemental doses every 12 h through 5 days, producing plasma levels in the therapeutic range. A slight, transient elevation in one or both serum transaminase values was observed in 6 of the 15 subjects treated with 4-MP. This effect was not dose related nor apparently mediated through a hypersensitivity reaction. Serum triglyceride levels were increased in 30% of 4-MP treated subjects, but also in 25% of the placebo subjects. 4-MP treatment did not produce any other significant changes in objective clinical parameters nor in subjective side effects. The results suggest that a mild, transient increase in liver function tests might be observed in some subjects treated with multiple doses of 4-MP. Nevertheless, the slower elimination rate and lesser degree of toxicity of 4-MP would make it preferable to ethanol in therapy of these poisonings. .A Jacobsen D; Sebastian CS; Barron SK; Carriere EW; McMartin KE. .I 275648 .U 91010578 .S J Emerg Med 9101; 8(4):463-6 .M Adult; Case Report; Coronary Disease/DI; Diagnosis, Differential; Dyspnea/CO; Electrocardiography/*; Human; Male; Tachycardia, Supraventricular/CO/DT/*PP; Verapamil/TU. .T Posttachycardia T-wave changes. .P JOURNAL ARTICLE. .W A 25-year-old previously healthy man presented to the emergency department with a tachydysrhythmia. After pharmacological intervention, the patient's rhythm converted to normal sinus and symmetrically inverted T-wave changes were noted. Although asymptomatic after conversion, the patient was admitted to the hospital and monitored for two days to rule out cardiac ischemia correlating with the T-wave changes. The patient was ultimately discharged in good health. A review of the emergency medical literature fails to reveal examples of post-tachycardic T-wave changes that may simulate myocardial ischemia but be of no clinical significance. .A Propp DA; Maloney W. .I 275649 .U 91010579 .S J Emerg Med 9101; 8(4):467-76 .M Aorta, Thoracic/*IN/RA; Aortic Rupture/ET/*RA; Brachiocephalic Trunk/*IN; Human; Mediastinum/RA; Thoracic Radiography; Tomography, X-Ray Computed; Wounds, Nonpenetrating/*RA. .T The normal mediastinum in blunt traumatic rupture of the thoracic aorta and brachiocephalic arteries. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W In a review of 52 articles, published between 1953 and 1989, 656 patients with blunt traumatic rupture of the thoracic aorta or brachiocephalic arteries were identified. Of these, 608 (92.7%) had an abnormal mediastinum on initial chest radiographs obtained in the emergency department, thus allowing early detection of the vascular injury. Unfortunately, 48 (7.3%) of these patients had a normal mediastinum on their initial chest radiographs. This appears to occur when the traumatic pseudoaneurysm is not accompanied by associated mediastinal hemorrhage or hematoma formation, and the pseudoaneurysm is either small or is situated in such a way that it does not alter the mediastinal contour. The use of accessory clinical and radiographic signs to indicate the need for aortography has been shown to be of very low yield, but would have allowed the early detection of an additional 5.6% of the reported cases. Performing aortography solely on the basis of a history of major decelerating blunt trauma to the thorax remains the only way, in the acute emergency department setting, to detect the 1.7% of patients with aortic or brachiocephalic arterial rupture who have no mediastinal abnormality or accessory clinical or radiographic signs of vascular injury. There is evidence from the literature, however, to suggest that the evaluation of serial chest radiographs obtained at close intervals for the first month following trauma for the development of mediastinal abnormality or large hemothorax is an acceptable alternative to the routine performance of aortography in those blunt chest trauma victims with no clinical or radiographic suspicion of vascular injury. .A Woodring JH. .I 275650 .U 91010580 .S J Emerg Med 9101; 8(4):477-84 .M Adult; Aorta, Thoracic/*IN/RA/SU; Aortic Rupture/CO/RA/*SU; Cardiac Tamponade/ET; Case Report; Human; Male; Pericardial Effusion/ET; Postoperative Complications; Respiratory Distress Syndrome, Adult/ET. .T Chest injury with complication in a 30-year-old man following a motor vehicle accident [clinical conference] .P CLINICAL CONFERENCE; JOURNAL ARTICLE. .A Scott SK. .I 275651 .U 91010581 .S J Emerg Med 9101; 8(4):485-90 .M Costs and Cost Analysis; Decision Making; Emergency Medical Services/*ST; Emergency Service, Hospital/*OG; Hospital Design and Construction; Hospital Units/*/EC; Human; Insurance, Health, Reimbursement; Patient Advocacy; Quality Assurance, Health Care. .T Observation units: boom or bust for emergency medicine [see comments] .P JOURNAL ARTICLE. .W Observation units (OBS) are becoming a common addition to the emergency department. The diagnostic and socioeconomic categories of patients admitted to the OBS unit resemble those seen in the emergency department. There are many advantages and disadvantages in establishing such a unit. Although OBS units provide improved patient care, current difficulties in reimbursement may delay their widespread acceptance. .A Zun L. .I 275652 .U 91010582 .S J Emerg Med 9101; 8(4):491-2 .M Emergency Medicine/*IS; Human; Ultrasonography/*. .T Emergency department ultrasound: is it really time for real time? [editorial] .P EDITORIAL. .A Abbott J. .I 275653 .U 91010583 .S J Emerg Med 9101; 8(4):493 .M Costs and Cost Analysis; Emergency Medicine/*MT; Emergency Service, Hospital/*OG; Hospital Units/*/EC; Human. .T An observation unit--essential to the safe and effective practice of emergency medicine [editorial] .P EDITORIAL. .A Markovchick V. .I 275654 .U 91010584 .S J Emerg Med 9101; 8(4):495 .M Emergency Medicine/*MT; Emergency Service, Hospital/*OG; Health Services Misuse; Hospital Units/*/UT; Human. .T Observation units: boom or bust for emergency medicine [editorial] .P EDITORIAL. .A Kercher EE. .I 275655 .U 91010585 .S J Emerg Med 9101; 8(4):497 .M Emergency Medicine/*MT; Emergency Service, Hospital/OG/*TD; Hospital Units/*UT; Human; Length of Stay. .T Observation units: another cause for early retirement of emergency physicians [editorial] .P EDITORIAL. .A Mathews J. .I 275656 .U 91010586 .S J Emerg Med 9101; 8(4):499-500 .M Adult; Case Report; Electric Countershock/*IS; Heart Arrest/*TH; Human; Male; Restraint, Physical/*IS; Social Control, Formal; Suicide, Attempted. .T Therapeutic use of an electronic immobilization device [letter] .P LETTER. .A Gushee DE; Dedolph R. .I 275657 .U 91010587 .S J Emerg Med 9101; 8(4):500-3 .M Drug Interactions; Human; Theophylline/*PD. .T Concerning drug interactions with theophylline [letter; comment] .P COMMENT; LETTER. .A Zucchero FJ; Hogan MJ. .I 275658 .U 91010588 .S J Emerg Med 9101; 8(4):503-5 .M Autoanalysis/*IS; Emergency Medicine/*IS; Emergency Service, Hospital; Human; Time Factors. .T The QBC2 analyzer in the emergency department [letter] .P LETTER. .I 275659 .U 91010590 .S J Emerg Med 9101; 8(4):506 .M Emergency Medicine/*TD; Emergency Service, Hospital/*UT; Human; Philosophy, Medical/*. .T When your emergency department is busy it tends to get busier [letter] .P LETTER. .A Keller RL. .I 275660 .U 91010591 .S J Emerg Med 9101; 8(4):507-11 .M Allied Health Personnel/*; Colorado; Curriculum; Emergency Medical Services/*MA; Emergency Medicine/*ED; Human; Internship and Residency/*; Quality Assurance, Health Care. .T The emergency medicine resident as paramedic: a prehospital in-field rotation. .P JOURNAL ARTICLE. .W Prehospital care has undergone a significant evolution during the past two decades and has been transformed from a transportation service into an advanced life support (ALS) delivery system. Crucial to the quality of such a program is physician knowledge and medical control. We describe a formal, one-month prehospital rotation for emergency medicine residents. The resident physician is exposed to a number of varying emergency medical services (EMS) systems, administrative experiences, and most uniquely, functions as a paramedic within our own ALS EMS system. In this manner, we believe the resident best obtains an understanding of the environment, attitudes, and behavior of prehospital personnel. .A Dinerman N; Pons PT; Markovchick V. .I 275661 .U 91010592 .S J Emerg Med 9101; 8(4):513-9 .M Curriculum; Dermatology/*ED; Emergency Medicine/*ED; Internship and Residency/*. .T Objectives to direct the training of emergency medicine residents on off-service rotations: dermatology. .P JOURNAL ARTICLE. .W This is the fifth in a continuing series of objectives to direct resident training in emergency medicine. Approximately 50% of resident experience and training in emergency medicine takes place outside of the direct control and influence of full-time emergency medicine faculty. To gain some direction and control over these off-service rotations, objectives and references are offered here. Objectives for a dermatology rotation as well as contents and references are presented. .A Eilers MA; Sheets CA; Chapman J; Hamilton GC. .I 275662 .U 91010609 .S Infect Dis Clin North Am 9101; 4(3):361-550 .M Human; Osteomyelitis/*. .T Osteomyelitis. A symposium on Bone and Joint Infections--New Perspectives. Pittsburgh, October 12-13, 1989. Proceedings. .P OVERALL. .I 275663 .U 91010610 .S Infect Dis Clin North Am 9101; 4(3):361-76 .M Arthritis, Infectious/EP; Bone Diseases/*EP; Cross Infection/*EP; Female; Human; Infection/*EP; Joint Diseases/*EP; Male; Osteomyelitis/EP; Tuberculosis, Osteoarticular/EP. .T Epidemiology in bone and joint infection. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W The studies of community-acquired infection indicate the importance of the environment in which the host-pathogen interaction takes place. Whereas the high incidence rates at the extremes of life are compatible with a hypothesis of diminished immune competence, the varying rates of acute osteomyelitis during growth, and its predominantly metaphyseal site, suggest that further studies of the molecular biology of this rather specific infection would be revealing. Molecular biology has a role, too, in improving understanding of the epidemiology of resistance and pathogenicity in hospital-acquired infections. Although antibiotic prescription and other medical practices influence the environment profoundly, we should remember that we may be experiencing long-term trends beyond our present understanding. As more and more reconstructive bone and joint surgery is carried out, careful observational epidemiology remains a vital tool. .A Gillespie WJ. .I 275664 .U 91010611 .S Infect Dis Clin North Am 9101; 4(3):377-90 .M Animal; Chickens; Disease Models, Animal/*; Dogs; Guinea Pigs; Osteomyelitis/*; Rabbits; Rats. .T Animal models of osteomyelitis. Knowledge, hypothesis, and speculation. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Each animal model has provided insights. Particularly important was the considerable resistance of bone to infection without manipulation (no morrhuate, fracture, rod, wax, or prosthesis). Such perturbations allow bone infection with much smaller inocula. Typical inocula decreases are 1000 to 10,000 fold. Staphylococci may have a selective advantage in bone because of specialized or tropic binding, perhaps to cartilage or collagen. Osteoclast-induced resorption of hydroxyapatite might explain the distribution of some osteomyelitis. Increased osteoclast activity could link the susceptible metaphyseal regions, the repetitively traumatized diabetic foot, a history of blunt bone trauma, fracture, and perhaps even nearby soft tissue infection. Diagnosis remains difficult; gallium-67 and indium111 labeled WBC probably deserve additional investigation. Therapeutic failures in the rabbit and rat models mirror clinical experience. Clindamycin, rifampin, and quinolones are promising. Neither systemic nor local antimicrobial prophylaxis is well studied yet. .A Rissing JP. .I 275665 .U 91010612 .S Infect Dis Clin North Am 9101; 4(3):391-408 .M Antibiotics/*PD; Bacteria/*DE; Bacterial Adhesion/*; Drug Resistance, Microbial; Human; Osteomyelitis/*MI. .T Musculoskeletal infection, microbial adhesion, and antibiotic resistance. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Osteomyelitis and intra-articular infection are septic diseases that present pathogenic features characteristic of molecular mechanisms involving adhesion to substrata. In this review, mechanisms of microbial adhesion to bone and cartilage as substrata are presented and related to host tissue response and to antibiotic treatment. .A Gristina AG; Naylor PT; Myrvik QN. .I 275666 .U 91010613 .S Infect Dis Clin North Am 9101; 4(3):409-32 .M Cellulitis/*ET; Diabetes Mellitus/*CO; Foot Diseases/*ET; Human; Osteomyelitis/*ET; Skin Ulcer/*ET. .T The diabetic foot. Soft tissue and bone infection. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Diabetic patients, as a consequence of various neurologic, vascular, and metabolic perturbations, are at high risk for developing infections of the soft tissue and bones of the feet. The microbial etiology of soft tissue in infections is best determined by cultures of a tissue curetting or aspiration, rather than a swab. Aerobic gram-positive cocci are the major pathogens in diabetic foot infections; these may be the sole isolate(s) in acute uncomplicated infections, but they are usually accompanied by aerobic gram-negative bacilli or anaerobes in chronic or previously treated infections. Carefully selected patients with mild infections can be treated as outpatients with oral antibiotics, but others require hospitalization and broad-spectrum parenteral antibiotics. Bone infections are frequently diagnosed on the basis of roentgenographs and nuclear medicine scans, but these methods are often inaccurate, and bone cultures should be obtained whenever possible. .A Lipsky BA; Pecoraro RE; Wheat LJ. .I 275667 .U 91010614 .S Infect Dis Clin North Am 9101; 4(3):433-40 .M Animal; Disease Models, Animal; Human; Hyperbaric Oxygenation/*; Osteomyelitis/*TH. .T Hyperbaric oxygen as adjunctive therapy for osteomyelitis. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Mechanistically, hyperbaric oxygen (HBO) appears useful for the treatment of osteomyelitis. HBO increases the oxygen tension in infected tissue, including bone. An adequate oxygen tension is necessary for oxygen-dependent killing of organisms by the polymorphonuclear leukocytes and for fibroblast activity leading to angiogenesis and wound healing. HBO has a direct bacteriocidal or bacteriostatic effect on anaerobic organisms. In addition, HBO augments the killing of Pseudomonas aeruginosa by the aminoglycoside--tobramycin. At the University of Texas Medical Branch at Galveston, adjunctive HBO is used for the Cierny Mader stage 3B and 4B osteomyelitis. .A Mader JT; Adams KR; Wallace WR; Calhoun JH. .I 275668 .U 91010615 .S Infect Dis Clin North Am 9101; 4(3):441-63 .M Bone and Bones/RA/*RI; Human; Magnetic Resonance Imaging; Osteomyelitis/*DI/RA/RI; Tomography, X-Ray Computed. .T Diagnostic imaging of osteomyelitis. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W There are many imaging procedures for diagnosing osteomyelitis, each with unique strengths and weaknesses. Plain radiographs are inexpensive and can be very accurate but may provide a delayed diagnosis. Computed tomography and magnetic resonance imaging are both excellent at differentiating soft tissue infection from osteomyelitis. Computed tomography, magnetic resonance imaging, and bone scans are accurate diagnostic tools for use when the bone has not be violated by surgery, trauma, or other structural alterations. When such changes are present, an Indium-111 leukocyte or Indium-111 polyclonal antibody study may be necessary for accurate diagnosis. .A Schauwecker DS; Braunstein EM; Wheat LJ. .I 275669 .U 91010616 .S Infect Dis Clin North Am 9101; 4(3):465-84 .M Antibiotics/TU; Human; Joint Prosthesis/*; Nomenclature; Surgical Wound Infection/*ET/PC/TH. .T Infection in total joint replacement. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Although a small number of infections in total joint replacements are blood borne from distant sources, most infections appear to have been derived at operation. Strenuous attempts to reduce this risk by cleaning the air in the wound environment, coupled with prophylactic antibiotics, have reduced infection rates by an order of magnitude in a decade. During that time the potential for exchange arthroplasty in established infection has been shown, and the results are encouraging. Rigorous infection control is the key to containing this difficult and expensive problem. .A Gillespie WJ. .I 275670 .U 91010617 .S Infect Dis Clin North Am 9101; 4(3):485-99 .M Antibiotics/PK/*TU; Human; Osteomyelitis/*DT. .T Antibiotic therapy for osteomyelitis. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Antibiotic therapy for osteomyelitis has dramatically changed within the past twenty years. The diagnostic criteria for osteomyelitis remain confusing to practicing physicians. Bone biopsy culture is now the standard for determining specific antimicrobial therapy. Many of the newest and most potent antimicrobials are now used to treat the increasingly broad bacterial spectrum of etiologies of osteomyelitis. There are tremendous economic incentives for outpatient and/or oral therapy. The third-generation cephalosporins and the new fluoroquinolones have replaced older, more toxic regimens, especially those containing aminoglycoside used to treat gram-negative osteomyelitis due to susceptible organisms. .A Gentry LO. .I 275671 .U 91010618 .S Infect Dis Clin North Am 9101; 4(3):501-12 .M Debridement/*; Human; Lasers/DU; Osteomyelitis/*SU. .T Surgical approaches in osteomyelitis. Use of laser Doppler flowmetry to determine nonviable bone. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W The surgical management of osteomyelitis includes radical debridement on nonviable bone. Laser Doppler flowmetry is a method for directly assessing the functional microcirculation in bone. The early results of the use of this technique as a surgical adjunct in the management of osteomyelitis are promising. .A Swiontkowski MF. .I 275672 .U 91010619 .S Infect Dis Clin North Am 9101; 4(3):513-22 .M Acute Disease; Child; Child, Preschool; Human; Infant; Osteomyelitis/*. .T Acute osteomyelitis in children. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Although relatively uncommon, osteomyelitis is an important disease because of the potential for chronicity or permanent sequelae. Diagnostic methods, the spectrum of the disease, and clinical situations that merit special consideration are reviewed in this article. .A Nelson JD. .I 275673 .U 91010620 .S Infect Dis Clin North Am 9101; 4(3):523-38 .M Arthritis, Infectious/DI/*ET/TH; Human. .T Infectious arthritis. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Any patient who presents with an acute monarticular arthritis, especially a new asymmetric effusion with underlying joint disease, should be suspected of having a bacterial process. Because synovial fluid findings (leukocyte counts and glucose) may not be predictive of infection, bacteriologic analysis by smear and culture is necessary in the evaluation of any new synovial effusion. A chronic monarticular process is highly likely to be infectious also, but mycobacterial or fungal etiologies frequently require appropriate culture of synovial tissue in addition to processing fluid. Acute polyarticular syndromes are seen as manifestations of disseminated gonococcal infections (DGI) and certain viral infections in adults. Diagnostic clues include historic and physical findings (exposure history and type of rash). The major pathogen in adults remains Staphylococcus aureus, so initial therapy is directed at this organism unless urinary tract infection is present also. Proper recommended therapy for DGI is ceftriaxone because penicillin-resistant strains are present in many urban centers. Early recognition and treatment of bacterial arthritis may prevent poor outcome, particularly in elderly patients or those with underlying joint diseases. For chronic mycobacterial or fungal infections, surgery may need to be combined with medical management. .A Smith JW. .I 275674 .U 91010621 .S Infect Dis Clin North Am 9101; 4(3):539-50 .M Diagnosis, Differential; Human; Osteomyelitis/DI/*ET/TH; Prognosis; Spinal Diseases/DI/*ET/TH. .T Vertebral osteomyelitis. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Vertebral osteomyelitis can be caused by a variety of microorganisms. The hematogenous pyogenic form is characteristically a disease of people over age 50, predominantly in the male population, and most frequently caused by S. aureus. In IVDAs, however, younger patients and a heavier predominance of males are seen, and P. aeruginosa is one of the most commonly seen pathogens. The disease is generally monomicrobial, unless it is secondary to a contiguous process such as a pressure sore, in which polymicrobial infection with participation of anaerobes is the general rule. Lumbar, greater than thoracic, greater than cervical involvement is the rule in the general population, but cervical spine involvement is frequently seen more often than thoracic involvement in IVDAs. Diabetic patients are over-represented among patients with vertebral osteomyelitis, and they also have a tendency for higher morbidity and mortality. Simultaneous involvement of adjacent vertebral end plates and the intervening disk is the general rule. The vertebrae are generally involved, and the posterior elements of the spine are involved infrequently. Posterior element involvement is seen more commonly in actinomycosis, coccidioidomycosis, and neoplasms. Newer diagnostic modalities, such as CT, MRI, and radionuclide scans, may detect the disease earlier than conventional radiographs. Immunobilization by bed rest and appropriate antimicrobial therapy are generally sufficient in the therapy of pyogenic, as well as tuberculous, vertebral osteomyelitis. In selected circumstances, such as in the presence of marked instability of the spine, the presence of new neurologic deficits, or with progression of previous neurologic deficits, surgical intervention may be necessary. With prompt diagnosis and proper management, the prognosis should generally be good. .A Sapico FL; Montgomerie JZ. .I 275675 .U 91010705 .S J Immunol 9101; 145(8):2390-6 .M Antibodies, Monoclonal/IM; Antigens, CD/*PH; Antigens, Differentiation/*PH; Antigens, Differentiation, T-Lymphocyte/PH; Cell Division; Cell Line; Flow Cytometry; Human; HLA-D Antigens/AN; In Vitro; Killer Cells, Natural/IM; Lymphocyte Transformation/*; Plasma Cells/IM; Receptors, Antigen, T-Cell/PH; Receptors, Immunologic/PH; Receptors, Interleukin-2/AN; Support, Non-U.S. Gov't; T-Lymphocytes/*IM; Tumor Cells, Cultured. .T Involvement of the multilineage CD38 molecule in a unique pathway of cell activation and proliferation. .P JOURNAL ARTICLE. .W We report clear evidence that the interaction of the CD38 molecule with the specific mAb A10 on normal human cells and lines modulates the expression of surface activation markers relevant to T, NK, and plasma cell biology and functions. Moreover A10 mAb binding is followed by proliferation effects on all the target cells analyzed, and the phenomenon is accessory cell and IL-2 dependent. The effects of A10 mAb synergizing both CD2 and CD3 activation pathways indicate that CD38 signal transduction mechanism(s) are apparently different from the aforementioned. Nevertheless the decreased A10-driven proliferation after CD3-Ti modulation suggests a possible functional interdependence between these activation pathways. Taken together, the results indicate that the CD38 molecule might play a physiologic role in T, NK, and plasma cell regulation. .A Funaro A; Spagnoli GC; Ausiello CM; Alessio M; Roggero S; Delia D; Zaccolo M; Malavasi F. .I 275676 .U 91010706 .S J Immunol 9101; 145(8):2397-405 .M Animal; Antigen-Presenting Cells/IM; Antigenic Determinants; B-Lymphocytes/*IM; Cell Differentiation; Haptens; Helper Cells/IM; Hemocyanin/IM; IgG/BI; Immunologic Memory/*; Immunosuppression; Lymphocyte Transformation; Mice; Mice, Inbred DBA; Spleen/CY; Support, Non-U.S. Gov't; Trinitrobenzenes/IM. .T Clonal anergy of memory B cells in epitope-specific regulation. .P JOURNAL ARTICLE. .W Immunization of carrier (keyhole limpet hemocyanin (KLH)) primed mice with the hapten-carrier TNP-KLH induces specific suppression for the IgG anti-TNP-response without interfering with the response to epitopes on the carrier molecule. To examine the status of hapten-specific memory B cells from suppressed mice, highly enriched populations of TNP-specific memory B cells were purified from the spleen of TNP-KLH (control) or KLH/TNP-KLH (suppressed) immunized mice and tested in vitro for their ability to respond to TD or TI (TNP-KLH, TNP-LPS) antigenic challenge in presence of a KLH-specific Th cell line. Similar numbers of TNP-specific B cells with the characteristics of memory B cells were obtained from control and suppressed mice. TNP-specific B cells from suppressed mice could be triggered to IgG production by TNP-LPS but had an impaired ability to differentiate into IgG-secreting cells in response to TNP-KLH. This impaired IgG response to TNP-KLH was not due to an active suppression by a subset of TNP-specific B cells, or to an impedence of memory cells to a class switching but to an intrinsic memory B cell defect. TNP-specific B cells from suppressed mice were as efficient as memory B cells from control mice to present TNP-KLH to KLH-specific Th cells and to proliferate in response to T cell help. Our data support the view that the effector mechanism of epitope specific regulation does not interfere with the development of hapten-specific memory B cells but that these cells have an intrinsic defect that prevents their differentiation into active IgG antibody secreting cells in response to a T-dependent antigenic challenge. .A Galelli A; Charlot B. .I 275677 .U 91010707 .S J Immunol 9101; 145(8):2406-14 .M Animal; Antigens, CD4/AN; Antigens, Differentiation, T-Lymphocyte/AN; Antigens, Surface/*AN/GE; Blotting, Northern; Cell Differentiation; Flow Cytometry; Gene Expression; Lymphocyte Transformation; Lymphoid Tissue/CY; Lymphokines/BI; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Peyer's Patches/*CY/IM; Receptors, Antigen, T-Cell/AN; T-Lymphocyte Subsets/*CY/IM; T4 Lymphocytes/*CY/IM. .T T lymphocytes that express CD4 and the alpha beta-T cell receptor but lack Thy-1. Preferential localization in Peyer's patches. .P JOURNAL ARTICLE. .W Thy-1- T cells expressing CD4 and the alpha beta-TCR have been identified in murine lymphoid tissues. These cells are particularly prevalent in Peyer's patches (PP), representing 17 +/- 3% of PP CD4 T cells, whereas they are much less prevalent in spleen, lymph nodes, lamina propria, or peritoneum. Phenotypic studies of fresh-isolated PP T cells demonstrate that all PP CD4 T cells (both Thy-1- and Thy-1+) express CD3, alpha beta-TCR, and CD5 (Lyt-1), whereas none coexpress CD8 (Lyt-2). Thy-1- and Thy-1+ CD4 T cell lines generated from PP also coexpress CD3 and alpha beta-TCR, but are heterogeneous in expression of CD5 and again do not coexpress CD8. Further studies revealed that Thy-1- CD4+ T cells were not present in nude mice. Short term stimulation of Thy-1+ CD4+ PP T cells with anti-CD3 resulted in loss of Thy-1 in a substantial fraction of these cells. Functional studies of Thy-1- and Thy-1+ CD4+ PP T cells indicate that fresh-isolated Thy-1- CD4+ cells do not proliferate in response to insoluble anti-CD3 but do proliferate when stimulated with soluble anti-CD3 in the presence of feeder cells. In contrast, Thy-1+ CD4+ cells proliferate well to both stimuli. However, Thy-1- CD4+ PP T cells adapted to in vitro culture exhibit vigorous proliferative responses when stimulated with either form of anti-CD3. Evaluation of lymphokine secretion by fresh-isolated Thy-1- and Thy-1+ CD4+ PP T cells revealed that both make substantial amounts of IL-2; however, Thy-1- T cells made less IL-4 than their Thy-1+ counterparts. Neither population made IL-5 or IFN-gamma. Similarly, Thy-1- and Thy-1+ CD4 T cell lines made similar amounts of IL-2; again Thy-1- T cells made less IL-4; and in this case Thy-1- T cells made IL-5 albeit significantly less than the Thy-1+ cells. Finally, immunohistochemical studies suggested that many of the CD4+ T cells in PP germinal centers were Thy-1-, indicating that Thy-1- and Thy-1+ CD4 T cells differ in their distribution within the PP. These studies thus define a phenotypically and functionally distinct T cell population which is most prevalent in murine Peyer's patches. .A Harriman GR; Lycke NY; Elwood LJ; Strober W. .I 275678 .U 91010710 .S J Immunol 9101; 145(8):2427-33 .M Animal; Antibody Formation/DE; B-Lymphocytes/*IM; Cell Differentiation/DE; Dextran Sulfate/*PD; Female; In Vitro; Lipopolysaccharides/PD; Lymphocyte Transformation/*DE; Lymphokines/PD; Rats; Rats, Inbred Lew; Salmonella typhimurium/IM; Support, U.S. Gov't, Non-P.H.S.; Time Factors. .T Polyclonal activation of rat B cells. II. Dextran sulfate as a cofactor in mitogen-induced and antigen-induced differentiation of rat B lymphocytes. .P JOURNAL ARTICLE. .W Salmonella typhimurium mitogen (STM) is a polyclonal activator of rat B lymphocytes, triggering them to proliferate, but not differentiate, to antibody-secreting cells. When lymphokines in the form of a supernatant from Con A-stimulated splenocytes (CAS) are added to B cell cultures activated by STM, only a small number of cells are driven to differentiate. Only with the addition of a third signal provided by the polyanionic polysaccharide dextran sulfate (DXS) is significant rat B cell differentiation observed. In this study, we have shown that this requirement for DXS is not unique to the STM mitogen. LPS, Staphylococcus aureus Cowan I-fixed cells, and anti-Ig antibody all induced rat B cell proliferation with little differentiation, even in the presence of CAS. DXS was necessary to induce differentiation in all cultures costimulated with mitogen and CAS. The requirement for DXS for optimal B cell differentiation is also observed with other lymphokine preparations such as the supernatants from PMA-stimulated EL-4 cells and PHA-stimulated human T cells. Furthermore, this augmentative effect of DXS in rat B cell differentiation was not confined to polyclonal activation systems. Ag-specific IgG secretion was also increased when DXS was added to Ag and CAS costimulated cultures of B cells harvested from the draining lymph nodes of rats immunized with DNP-keyhole limpet hemocyanin. Within the polyclonal activation system, a method of staged additions of STM, DXS, and CAS to B cell cultures was used to investigate the role of DXS during B cell differentiation. Optimal differentiation occurred only when DXS was present in the B cell cultures in conjunction with CAS. The augmentation in differentiation seen with DXS did not appear to be due to the recruitment of an additional CAS-responsive B cell subset, because cycling, low density B cell blasts showed large increases in IgM secretion with subsequent exposure to DXS and CAS. These studies suggest tha DXS acts as a cofactor to various differentiation factors, augmenting polyclonal and Ag-specific rat B cell differentiation. The relevance of DXS to in vivo immune responses is discussed. .A Minchin SA; Leitenberg D; Stunz LL; Feldbush TL. .I 275679 .U 91010712 .S J Immunol 9101; 145(8):2440-7 .M Animal; B-Lymphocyte Subsets/IM; B-Lymphocytes/*IM; Interleukin-1/PD; Interleukin-4/PD; Interleukin-5/*PD; Lipopolysaccharides/PD; Lymph Nodes/*CY/IM; Lymphocyte Transformation/DE; Mice; Mice, Inbred Strains; Peritoneal Cavity/CY; Receptors, Mitogen/AN; Spleen/CY; Support, U.S. Gov't, P.H.S.. .T Germinal center cells are a major IL-5-responsive B cell population in peripheral lymph nodes engaged in the immune response. .P JOURNAL ARTICLE. .W Germinal center formation and the development of B cell memory in lymphoid tissue is a T cell-dependent process. The specific B cell-T cell interactions, and/or cytokines, resulting in germinal center cell growth have not yet been identified. Germinal center B cells were separated from other lymph node (LN) B cells by panning on peanut agglutinin (PNA)-coated dishes. Resulting fractions enriched for PNA+ (germinal center) B cells, and the PNA- (other) LN B cells from immune SJL mice were assayed for proliferation in the presence of cytokines. PNA+ and PNA- B cells responded equally to IL-4 in the anti-mu co-stimulator assay. In contrast, PNA+ B cells responded to murine (r)IL-5 or human B cell growth factor in the dextran sulfate (DxS) co-stimulator assay, to a much greater degree than did PNA- B cells. The same results were obtained with PNA+ and PNA- cells from LAF1 mice. Unfractionated LN B cells from nonimmunized SJL or BALB/c mice did not respond to IL-5 with or without DxS. B cell populations from BALB/c mice such as from spleen and peritoneal cavity, which are known to be high in Ly-1+B cells, responded to IL-5 alone, and more dramatically, to IL-5 as a co-stimulator with DxS. Such populations of cells from SJL mice, which are known to contain low numbers of Ly-1+B cells, responded markedly less. These results are consistent with those of others which show that in nonimmunized mice, Ly-1+B cells are a major IL-5 responsive subpopulation. IL-1 enhanced the proliferation of PNA+ cells in response to rIL-5 and had no effect on PNA- cells. IL-4 and IL-5 did not enhance each other's effects as co-stimulators of proliferation. In contrast to PNA+ B cells from immune LN, B cells activated by Escherichia coli endotoxin exhibited no responses to rIL-5. The present results indicate that in immune LN, PNA+, germinal center B cells constitute a prominent IL-5-responsive population. .A Rabinowitz JL; Tsiagbe VK; Nicknam MH; Thorbecke GJ. .I 275680 .U 91010715 .S J Immunol 9101; 145(8):2459-64 .M Acquired Immunodeficiency Syndrome/*IM; Calcitriol/*PD; Cells, Cultured; Chemotaxis, Leukocyte/*DE; Dose-Response Relationship, Drug; Human; In Vitro; Monocytes/*DE/ME; N-Formylmethionine Leucyl-Phenylalanine/PD; Receptors, Immunologic/ME; Support, Non-U.S. Gov't. .T Augmentation of monocyte chemotaxis by 1 alpha,25-dihydroxyvitamin D3. Stimulation of defective migration of AIDS patients. .P JOURNAL ARTICLE. .W Preincubation for 20 h with 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) markedly augmented the chemotactic responsiveness of human blood monocytes to the classical chemoattractant, FMLP. A modest enhancement of monocyte spontaneous locomotion in the absence of chemoattractants was also observed. Maximal increase of monocyte migration was observed after pretreatment with 10(-9) M 1,25(OH)2D3 and was detectable at FMLP concentrations ranging from 10(-10) to 10(-7) M. Pretreatment with 1,25(OH)2D3 augmented the number of monocyte high affinity FMLP receptors (1500 +/- 220 and 3800 +/- 300 sites per cell for untreated and 1,25(OH)2D3-pretreated cells, respectively) with no significant changes in Kd values (2 +/- 0.5 nM and 4 +/- 1 nM, for untreated and 1,25(OH)2D3-pretreated monocytes). Enhanced chemotaxis was not restricted to FMLP, because 1,25(OH)2D3-treated monocytes showed enhanced migration also in response to activated C components and chemotactic cytokines. In agreement with previous observations, monocytes from AIDS patients showed defective migration capacity. In vitro exposure to 1,25(OH)2D3 stimulated monocyte migration in all 10 patients examined with considerable quantitative differences among individuals. Regulating the responsiveness of mature monocytes to chemo-attractants, 1,25(OH)2D3, produced systemically or in situ by immunocompetent cells, could play a role in the regulation of the recruitment of monocytes at sites of inflammation, cell-mediated immunity, or bone resorption. The potential of 1,25(OH)2D3 as a restorative agent under conditions of defective phagocyte recruitment deserves further exploration. .A Girasole G; Wang JM; Pedrazzoni M; Pioli G; Balotta C; Passeri M; Lazzarin A; Ridolfo A; Mantovani A. .I 275681 .U 91010716 .S J Immunol 9101; 145(8):2465-73 .M Animal; Animals, Newborn/*IM; Antibodies, Antinuclear/IM; Antibodies, Monoclonal/AD; Antigen-Antibody Complex/ME; Autoimmune Diseases/*IM; B-Lymphocytes/IM; Cytotoxicity, Immunologic; Dose-Response Relationship, Immunologic; DNA, Single-Stranded/IM; H-2 Antigens/AN; Histocompatibility Antigens Class II/AN; Immune Tolerance/*; Immunoglobulin Isotypes/BI; Interleukin-4/*PH; Mice; Mice, Inbred Strains; Platelet Count; Spleen/IM; Support, Non-U.S. Gov't; T-Lymphocytes, Cytotoxic/IM; Thymus Gland/IM. .T In vivo effects of anti-IL-4 monoclonal antibody on neonatal induction of tolerance and on an associated autoimmune syndrome. .P JOURNAL ARTICLE. .W The role of IL-4 in the cellular interactions leading to the induction of CTL tolerance to H-2b alloantigens and to the development of a lupus-like autoimmune disease in BALB/c mice after neonatal injection with (C57BL/6 x BALB/c)F1 cells was investigated in vivo by using an anti-IL-4 mAb. Treatment of F1 cell-injected BALB/c mice with 15 mg of anti-IL-4 mAb was shown to interfere with tolerance induction, as assessed by the high percentages of H-2b target cell lysis and the very low or undetectable levels of B cell chimerism markers observed in these mice. Treatment with 4.5 mg of anti-IL-4 mAb interfered with tolerance induction only in one-third of F1 cell-injected BALB/c mice, but that dose induces specific modulations of the autoimmune manifestations in all mice, leading to the nearly complete prevention of the disease. In particular, the production of anti-ssDNA IgG1 and of total IgG1 and IgE antibodies was seriously affected by the treatment, as well as the proliferation and membrane Ia and K expression of F1 donor splenic cells and thymic APC. Treatment of F1 cell-injected BALB/c mice between 24 and 48 h of life with 0.5 mg of anti-IL-4 mAb did not interfere with tolerance induction, but had similar effects on the autoimmune syndrome as treatment with 4.5 mg. These results suggest that, after F1 cell injection of newborn mice, IL-4 plays an important role in the cellular interactions leading to the induction of tolerance to the corresponding alloantigens and to the development of the associated autoimmune syndrome. .A Schurmans S; Heusser CH; Qin HY; Merino J; Brighouse G; Lambert PH. .I 275682 .U 91010717 .S J Immunol 9101; 145(8):2474-81 .M Animal; Antigen-Presenting Cells/IM; Brain/*BS/IM; Cell Line; Encephalitogenic Basic Proteins/IM; Encephalomyelitis, Allergic/*IM; Endothelium, Vascular/*IM; In Vitro; Lymphocyte Transformation; Ovalbumin/IM; Rats; Rats, Inbred Lew; Support, Non-U.S. Gov't; Tumor Necrosis Factor/AN; T4 Lymphocytes/*IM. .T Antigen-specific damage to brain vascular endothelial cells mediated by encephalitogenic and nonencephalitogenic CD4+ T cell lines in vitro. .P JOURNAL ARTICLE. .W Experimentally induced and naturally occurring inflammatory diseases of the central nervous system (CNS) are often associated with a breakdown of the blood-brain barrier and edema within the CNS itself. CD4+ T cells are now clearly implicated in the pathogenesis of the induced CNS disease, experimental autoimmune encephalomyelitis, and previous in vivo experiments had indicated that these cells may be capable of directly damaging the CNS vasculature. To assess the capacity of CD4+ T cells to damage brain vascular endothelial cells (EC) in vitro, two lines with specificity for myelin basic protein and OVA were prepared and added to cultures of EC. We show here that both lines, when added in a resting state, severely disrupt the EC monolayers in an Ag-specific manner. The interaction is dependent on the recognition of Ag in the context of MHC class II and is blocked in the presence of mAb specific for CD4. Addition of T cell lines preactivated on irradiated thymocyte APC caused a high level of Ag nonspecific damage to the EC, which was not blocked by the addition of anti-CD4 mAb. Supernatants derived from these latter cells did not alone damage the EC monolayers despite the presence of TNF activity suggesting that T cell-EC contact may be required for these cell lines to mediate their effector function. Both resting and preactivated lines adhered strongly to the EC in the absence of Ag. The capacity of CD4+ T cells to strongly adhere to, and disrupt the integrity of, brain vascular EC may be important in the early stages of CNS disease mediated by this cell type. .A Sedgwick JD; Hughes CC; Male DK; MacPhee IA; ter Meulen V. .I 275683 .U 91010718 .S J Immunol 9101; 145(8):2482-8 .M Animal; Antigens, Surface/*AN; Epidermis/*IM/PA; Female; Graft vs Host Disease/*IM/PA; Immunity, Cellular; Langerhans Cells/IM; Lymphocyte Subsets/IM; Mice; Mice, Inbred C57BL; Mice, Nude/IM; Support, Non-U.S. Gov't; Thymus Gland/*IM. .T Loss of epidermal integrity by T cell-mediated attack induces long term local resistance to subsequent attack. II. Thymus dependency in the induction of the resistance. .P JOURNAL ARTICLE. .W Our previous study showed that in cutaneous graft-vs-host disease (GVHD) induced by intradermal injection of autoreactive T cells the epidermal structures spontaneously recovered from the destruction became resistant to the subsequent attempts to induce the cutaneous GVHD and that the resistance correlated well with a 30-fold increase in the number of Thy-1+ epidermal cells (Thy-1+EC). We show that the resistance to the cutaneous GVHD was never induced in athymic nude mice and adult thymectomy lethal radiation and bone marrow reconstitution (ATXBM) mice under the same conditions, indicating that the induction of the resistance is dependent on the presence of thymus. A great increase in the number of Thy-1+EC was similarly observed in the epidermis of the athymic nude and ATXBM mice that spontaneously recovered from the cutaneous GVHD and that remained susceptible to the induction of the cutaneous GVHD. However, the results with B10Thy-1.1----B6 radiation chimeras clearly demonstrate that the vast majority of the increased Thy-1+EC found in the "susceptible" epidermis of the ATXBM mice were of donor bone marrow origin and there was no increase in the number of host-derived Thy-1+EC, whereas in the "resistant" epidermis of the XBM mice both Thy-1+EC populations were equally increased. The overall results indicate that the expansion of Thy-1+EC that mature in the thymus is crucial to the induction of the resistance, although the migration of bone marrow-derived Thy-1+EC precursors to the epidermis occurs quite independently of the presence of thymus. .A Shiohara T; Moriya N; Gotoh C; Hayakawa J; Ishikawa H; Saizawa K; Nagashima M. .I 275684 .U 91010721 .S J Immunol 9101; 145(8):2500-6 .M Animal; Antigens, Differentiation, B-Lymphocyte/PH; Bone Marrow/CY; Cytokines/PD; Dose-Response Relationship, Drug; IgE/IM; IgG/IM; Interleukin-3/BI/*PD; Interleukin-4/*BI; Lymphocytes, Null/*IM; Mice; Mice, Inbred BALB C; Receptor Aggregation; Receptors, Fc/*PH; Spleen/CY. .T IL-3 promotes production of IL-4 by splenic non-B, non-T cells in response to Fc receptor cross-linkage. .P JOURNAL ARTICLE. .W A spleen cell population that lacks CD3, CD4, CD8, Thy-1, B220, and class II major histocompatibility complex cell-surface markers (non-B, non-T cells) produces IL-4 when cultured in wells coated with IgE. Their production of IL-4 in response to plate-bound (PB)-IgE is strikingly enhanced by IL-3, and in the presence of IL-3, these cells also produce IL-4 in response to PB-IgG2a. The effect of IL-3 is not mimicked by IL-1, IL-2, IL-5, IL-6, IL-7, granulocyte-macrophage CSF (GM-CSF) or IFN-gamma. Non-B, non-T cells cultured with IL-3 for 12 h acquire the capacity to produce enhanced amounts of IL-4 in response to subsequent culture with PB-Ig even if IL-3 is omitted from the second culture. Irradiated cells also respond to IL-3 with enhanced capacity to produce IL-4 to PB-Ig, indicating that cell proliferation is not required for the effect of IL-3. The IL-3 effect can be obtained in vivo; treatment of mice with a total dose 90,000 U of synthetic IL-3 over a 3-day period results in the presence of splenic and peritoneal cavity non-B, non-T cells that produce enhanced amounts of IL-4 in response to PB-Ig. The FcR that mediates the response to PB-IgE appears to be Fc epsilon RI because cells can be sensitized with IgE anti-DNP mAb, washed, cultured for 15 h at 37 degrees C, washed again, and stimulated to produce IL-4 with 0.1 to 1 ng/ml of TNP10-OVA. IL-3 does not appear to mediate its function by increasing the number of Fc epsilon RI because it can exert its effect when cultured with non-B, non-T cells after they have been sensitized with IgE anti-DNP. However, IL-3 pretreatment does affect the signaling process in that non-B, non-T cells sensitized with IgE anti-DNP show strikingly reduced production of IL-4 to concentrations of TNP10-OVA of 100 ng/ml or more whereas cells pretreated with IL-3 show little or no diminution in IL-4 production at concentrations of TNP10-OVA up to 1 microgram/ml. .A Le Gros G; Ben-Sasson SZ; Conrad DH; Clark-Lewis I; Finkelman FD; Plaut M; Paul WE. .I 275685 .U 91010722 .S J Immunol 9101; 145(8):2507-13 .M Antibodies, Monoclonal; Blotting, Northern; C-Reactive Protein/*BI/GE; Hepatoma; Human; Interleukin-1/PD; Interleukin-6/PD; Molecular Weight; Recombinant Proteins; RNA, Messenger/GE; Support, U.S. Gov't, P.H.S.; Transforming Growth Factor beta/*PD; Tumor Cells, Cultured. .T Regulation of cytokine-induced human C-reactive protein production by transforming growth factor-beta. .P JOURNAL ARTICLE. .W Transforming growth factor-beta (TGF-beta) modified production of the major human acute phase reactant, C-reactive protein (CRP), induced by the inflammatory cytokines, IL-1 beta or IL-6. CRP mRNA accumulation in the hepatoma PLC/PRF/5 cell line was slightly more rapid, but of smaller magnitude in response to IL-1 beta (fourfold increase) than to IL-6 (10-fold increase); however, the amount of CRP protein accumulating in the culture medium was similar for both cytokines. TGF-beta at concentrations greater than or equal to 0.1 pg/ml inhibited the induced IL-1 or IL-6 CRP production; whereas concentrations less than 0.1 pg/ml slightly enhanced CRP synthesis. Addition of TGF-beta to the cultures up to 16 h after the PLC/PRF/5 cells were already exposed to IL-1 or IL-6 resulted in the cessation of CRP production. CRP mRNA accumulated in hepatoma cells treated with both TGF-beta and IL-6, although CRP protein synthesis was inhibited. A similar pattern of inhibition of CRP production by TGF-beta occurred when Hep 3B.2 cells were treated with a mixture of IL-1 and IL-6. Enhanced production of CRP was observed only when TGF-beta was added to the cells before the cytokine. This enhanced CRP response was sensitive to cycloheximide. TGF-beta added along with IL-6 inhibited the metabolic labeling of CRP with [35S]methionine; however, enhanced incorporation of [35S]methionine into CRP was observed when the cells were exposed to TGF-beta before IL-6 addition. Therefore, TGF-beta is potentially a potent regulator of CRP synthesis by hepatocytes at the post-transcriptional level. .A Taylor AW; Ku NO; Mortensen RF. .I 275686 .U 91010723 .S J Immunol 9101; 145(8):2514-9 .M Arthritis, Rheumatoid/*IM/PA; Cell Division; Fibroblasts/CY; Human; In Vitro; Interleukin-1/*PD; Leukocytes, Mononuclear/ME; Lymphocyte Transformation; Macrophages/PH; RNA, Messenger/GE; Synovial Membrane/ME/PA; Transforming Growth Factor beta/GE/ME/*PD. .T Antagonistic and agonistic effects of transforming growth factor-beta and IL-1 in rheumatoid synovium. .P JOURNAL ARTICLE. .W We investigated potential mechanisms by which lymphocytes infiltrating rheumatoid synovium become immunosuppressed. In 20 of 22 synovial fluids and 12 of 13 synovial tissue culture supernatants, no IL-1 bioactivity could be detected in the thymocyte proliferation assay. These same preparations could, however, support proliferation of fibroblast monolayers, consistent with the presence of IL-1 and/or other fibroblast growth factors. Addition of either rheumatoid synovial fluids or synovial culture supernatants to exogenous IL-1 in the IL-1 bioassay caused marked inhibition of the assay indicative of an IL-1 inhibitor. This inhibition of IL-1 could be reversed by treating the effusions or supernatants with a neutralizing antibody to transforming growth factor-beta (TGF-beta). Furthermore, monocyte-macrophages isolated from rheumatoid synovial fluid constitutively released both latent and active TGF-beta in culture at levels sufficient to completely block the biologic activity of 100 U/ml IL-1. The production of substantial levels of TGF-beta by synovial macrophages, as well as the apparent ability of these inflammatory macrophages to activate latent TGF-beta, implicates TGF-beta not only as an important inhibitor of IL-1-induced lymphocyte proliferation, but also as a key cytokine in promoting synovial fibroblast hyperplasia and pathology. .A Wahl SM; Allen JB; Wong HL; Dougherty SF; Ellingsworth LR. .I 275687 .U 91010724 .S J Immunol 9101; 145(8):2520-6 .M Amino Acid Sequence; Cell Adhesion/*; Complement 1q/*PH; Cycloheximide/PD; Fibroblasts/*CY; Human; In Vitro; Molecular Sequence Data; Oligopeptides/ME; Receptors, Complement/*PH; Receptors, Immunologic/ME; Support, U.S. Gov't, P.H.S.. .T Participation of C1q and its receptor in adherence of human diploid fibroblast. .P JOURNAL ARTICLE. .W C1q binds through its collagen-like domain to specific surface receptors of fibroblasts and to adhesive elements of extracellular matrix including fibronectin, collagens, proteoglycans, and laminin. To determine whether C1q participates in fibroblast adhesion, cells in serum-free medium were plated on surfaces coated with purified C1q at physiologic ionic strength and pH. Surfaces coated with fibronectin or collagen type I served as positive controls, and those coated with BSA were negative controls. Substratum-adsorbed C1q promoted fibroblast adhesion to a maximum of 73% of available cells within 90 min at 37 degrees C. Adhesion was C1q concentration dependent, saturable, specific, and dependent on the collagen-like domain of the molecule. De novo protein synthesis plays a role in adhesion: pretreatment of fibroblasts with cycloheximide reduced adherence about 50% of controls. Addition of exogenous fibronectin, collagen type I, or C1q as soluble mediators did not affect adhesion of the cycloheximide-treated cells to C1q substrate. Adhesion could be accounted for primarily, although not completely, by the C1q receptors. Antibodies raised against the Raji cell C1q receptors (alpha C1qR Ab) specifically inhibited fibroblast adhesion to C1q substrates about 60% of controls. The binding of fibroblasts to C1q substrates could be inhibited about 24% of controls with the GRGDTP cell recognition peptide. GRGDTP and alpha C1q Ab had an additive effect on adhesion that was inhibited 77 to 80% of controls. We conclude from these data that aggregated rather than monomeric C1q may be the natural ligand of the fibroblast C1q receptor, and the biologic function of the receptor in cells of the connective tissue may be cell adhesion. .A Bordin S; Ghebrehiwet B; Page RC. .I 275688 .U 91010726 .S J Immunol 9101; 145(8):2533-8 .M Animal; Antibodies, Anti-Idiotypic/*IM; Antibodies, Monoclonal; Immunoglobulin Fragments/IM; Immunoglobulin Idiotypes/IM; Immunoglobulin Variable Region/ME; Immunoglobulins, Fab/ME; In Vitro; Macromolecular Systems; Mice; Polyethylene Glycols; Protein Binding; Solubility; Structure-Activity Relationship; Support, U.S. Gov't, P.H.S.. .T Self-binding antibodies (autobodies) form specific complexes in solution. .P JOURNAL ARTICLE. .W In this report we have shown that members of the murine self-binding antibody family, S107, form soluble complexes and precipitate under conditions in which non-self-binding antibodies remain in solution. Two approaches were used to demonstrate the self-association of autobodies: size-exclusion column chromatography and polyethylene glycol (PEG)-mediated precipitation assay. The anti-phosphorylcholine antibody T15 and two somatic variants, U4, which binds DNA, and U10, which has no identified specificity, produced larger precipitates in 10% PEG than other non-self-binding antibodies. The selectivity of PEG-mediated precipitation of self-binding antibodies is demonstrated by reduction of precipitation with specific haptens known to inhibit self-binding in solid-phase assays. Phosphorylcholine and nucleotides reduced precipitation of T15 and U4, respectively, but not U10. To rule out Fc-Fc mediated self-association in solution, we have also demonstrated self-complexing of F(ab')2 fragments of T15 using PEG. The self-binding locus was further dissected using peptides derived from V regions. A 24-residue peptide derived from the second hypervariable region of the VH of S107 specifically enhanced precipitation of T15, U4, and U10, but not other antibodies. These results provide evidence of a dormant potential of self-binding antibodies to precipitate under conditions that reduce the solubility of proteins. The implication of this potential is discussed with respect to pathological complex formation. .A Kaveri SV; Halpern R; Kang CY; Kohler H. .I 275689 .U 91010727 .S J Immunol 9101; 145(8):2539-44 .M Amino Acid Sequence; Antibodies, Monoclonal/*IM; Antigenic Determinants; Antigens, Bacterial/*IM; Bacterial Proteins/*IM; Blotting, Western; Cell Line; Cross Reactions; Human; HLA-B27 Antigen/*IM; In Vitro; Molecular Sequence Data; Peptides/CS/IM; Shigella flexneri/IM. .T Monoclonal antibodies against an HLA-B27-derived peptide react with an epitope present on bacterial proteins. .P JOURNAL ARTICLE. .W The role of molecular mimicry in the spondyloarthropathies was investigated with respect to the epitopes involved. mAb were produced against a synthetic peptide whose sequence was derived from a polymorphic region of the HLA-B27 molecule (amino acids 63-83). Two antibodies (J7F2 and H2B6) were selected for study on the basis of their ability to react with bacterial envelope proteins (ELISA) and B27-positive cells (immunofluorescence). J7F2 reacted preferentially with B27-positive cells and neither antibody reacted with MHC class I negative cells. Based on SDS-PAGE blot analysis of bacterial envelope proteins, the pattern of reactivity for both antibodies (against 36- and 19-kDa proteins) was the same as that for a third monoclonal produced against bacterial envelope and reactive with B27-positive cells. This apparent epitope similarity was investigated by using synthetic peptides to inhibit binding of the monoclonals. The B27 synthetic peptide and a smaller peptide derived from it were efficient inhibitors of antipeptide and antibacterial antibody binding to bacterial Ag and B27-positive cells. These studies provide insight into the molecular basis of cross-reactivity between bacterial proteins and MHC class I molecules. .A Raybourne RB; Williams KM. .I 275690 .U 91010730 .S J Immunol 9101; 145(8):2561-5 .M Azepines/PD; Chemotaxis, Leukocyte/*DE; Dose-Response Relationship, Drug; Endothelium, Vascular/PH; Human; In Vitro; Neutrophils/*PH; Platelet Activating Factor/CH/*PD; Receptors, Endogenous Substances/DE; Structure-Activity Relationship; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Time Factors; Triazoles/PD. .T Degree of platelet activating factor-induced neutrophil migration is dependent upon the molecular species. .P JOURNAL ARTICLE. .W Multiple molecular species of platelet activating factor (PAF) are produced as a result of inflammatory processes. PAF-induced neutrophil migration across endothelium is intrinsic to inflammatory responses. We therefore compared the ability of three naturally occurring PAF species (C16:0, C18:0, and C18:1), which only varied at carbon 1, to induce 51Cr-labeled human neutrophil migration across a naked 3-microns pore filter and human umbilical vein endothelial (HUVE) monolayers cultured on these filters. Time-course experiments indicated that all species of PAF tested induced significant neutrophil migration between 15 and 45 min. PAF-induced neutrophil migration through both filters alone and HUVE monolayers occurred at lower doses with C16:0 PAF. The rank order of chemotactic potency for the PAF species was C16:0 greater than C18:0 greater than C18:1 with both filters and endothelium coated filters as barriers. Intrinsic differences in the potency of these PAF molecular species to induce neutrophil chemotaxis were greater when HUVE cells were the barriers vs when filters alone were the barriers. Regardless of the molecular species used, at optimal PAF doses the degree of neutrophil migration through HUVE cells was often greater than that through filters alone. The specific PAF antagonist WEB 2086 inhibited neutrophil migration induced by all three PAF species equally. WEB 2086 pretreatment of the neutrophil or WEB 2086 coincubation with PAF, but not WEB 2086 pretreatment of the HUVE cell monolayers, significantly inhibited (65 to 80%) neutrophil migration. We conclude that the degree of PAF-induced neutrophil migration is dependent upon the molecular species of PAF. Moreover, the barrier through which the neutrophil must migrate appears to be important in influencing the overall chemotactic response to the various PAF species. .A Carolan EJ; Casale TB. .I 275691 .U 91010731 .S J Immunol 9101; 145(8):2566-70 .M Amino Acid Sequence; Animal; Comparative Study; Dose-Response Relationship, Drug; Gene Products, gag/*PD; Kinetics; Molecular Sequence Data; Peptides/CH/*PD; Phosphorylation; Protein Kinase C/*AI; Rats; Serum Albumin, Bovine; Structure-Activity Relationship; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Inhibition of protein kinase C by a peptide conjugate homologous to a domain of the retroviral protein p15E. .P JOURNAL ARTICLE. .W Retroviral infection is associated with immunosuppression, which has been shown to be due, in part, to the action of the envelope protein p15E. We studied a synthetic peptide (CKS-17) homologous to a highly conserved domain of the retroviral envelope protein p15E, which, when conjugated to BSA (CKS-17-BSA), can inhibit IL-1- and phorbol ester-mediated responses in cultured murine thymoma cells, and Ca2(+)- and phosphatidylserine-dependent protein kinase C (PKC) activity of cell homogenates. We characterized the mechanism of inhibition of PKC by the peptide. Using PKC purified from rat brain we found that CKS-17-BSA inhibited PKC-catalyzed Ca2(+)- and phosphatidylserine-dependent histone phosphorylation with an estimated ID50 of 4 microM. CKS-17-BSA did not inhibit the catalytic subunit of cAMP-dependent protein kinase. CKS-17-BSA also inhibited the Ca2(+)- and PS-independent activity of a catalytic fragment of PKC that was generated by limited trypsin treatment. However, CKS-17-BSA did not act as a competitive inhibitor of PKC with respect to ATP or phosphoacceptor substrate, despite the similarity between the CKS-17 sequence and substrates and pseudosubstrates of PKC. We conclude that this peptide homologue of a retroviral envelope protein has a novel mechanism of inhibition of PKC. .A Gottlieb RA; Kleinerman ES; O'Brian CA; Tsujimoto S; Cianciolo GJ; Lennarz WJ. .I 275692 .U 91010732 .S J Immunol 9101; 145(8):2571-80 .M Animal; Calcimycin/PD; Concanavalin A/PD; Diglycerides/PD; Electrophoresis, Gel, Two-Dimensional; Enzyme Activation; Forskolin/PD; Isoelectric Point; Lymphocyte Transformation/*; Mice; Mice, Inbred BALB C; Molecular Weight; Phosphoproteins/*ME; Protein Kinase C/*PH; Support, Non-U.S. Gov't; T-Lymphocytes/EN/PH; Tetradecanoylphorbol Acetate/PD. .T Analysis of the primary signals required for activation of the mitogenic pathway in murine thymocytes from protein phosphorylation patterns. .P JOURNAL ARTICLE. .W It has been proposed that phorbol esters and the Ca2+ ionophore A23187 are effective comitogens for some species of lymphocytes because together they mimic the normal secondary signals for cell activation by mitogens that cause phosphatidylinositol 4,5-bisphosphate (PtdInsP2) breakdown (e.g., anti-TCR and anti-Thy-1 antibodies and Con A). To test whether activation of protein kinase C and an increase in [Ca2+]i account for the activation of the mitogenic pathway in murine thymocytes by the mitogens that cause PtdInsP2 breakdown, the two-dimensional phosphorylation patterns generated by the three classes of mitogens (protein kinase C activator, Ca2+ ionophore, and activator of PtdInsP2 breakdown) and by activators of cAMP-dependent kinases have been compared. From the phosphorylation patterns, by which each mitogen could be distinguished reproducibly, it was concluded that: 1) The phosphorylation patterns generated by the mitogens that activate PtdInsP2 breakdown are only slightly affected by the removal of extracellular Ca2+ under conditions that abolish the normal rise in [Ca2+]i and do not therefore depend on the activation of Ca2(+)-dependent protein kinases. In contrast, the phosphorylation pattern generated by A23187 is totally dependent on extracellular Ca2+. 2) Neither A23187 nor the mitogens that activate PtdInsP2 breakdown nor activators of cAMP-dependent kinases caused significant activation of protein kinase C assayed by phosphorylation of the diagnostic proteins 80b and 78a. Consistent with this conclusion, only the phorbol esters or oleoyl acyl glycerol caused translocation of protein kinase C activity from the cytosolic to the membrane fraction. 3) Neither A23187 nor the mitogens that cause PtdInsP2 breakdown activated cAMP-dependent kinases. Taken together the data imply that the mitogens that cause PtdInsP2 breakdown must generate an additional, independent primary mitogenic signal. It is suggested that this signal may be the activation of tyrosine kinases (e.g., p56lck) via the TCR and working hypotheses for effective combinations of primary mitogenic signals that will activate DNA synthesis are developed. .A Hesketh R; Moore TA; Pennington SR; Smith GA; Metcalfe JC. .I 275693 .U 91010733 .S J Immunol 9101; 145(8):2581-7 .M Animal; Calcium/ME; Cytoplasm/ME; Eosinophils/EN/*PH; Guinea Pigs; Kinetics; Lactate Dehydrogenase/ME; Melitten/*PD; N-Formylmethionine Leucyl-Phenylalanine/*PD; Peritoneal Cavity/CY; Peroxidases/ME; Substance K/PD; Substance P/*PD; Superoxide/ME; Support, Non-U.S. Gov't; Thromboxane A2/ME. .T Characterization of eosinophil cell activation by peptides. Differential effects of substance P, melittin, and FMET-Leu-Phe. .P JOURNAL ARTICLE. .W The ability of three different peptides, substance P (SP), FMLP and melittin, to activate eosinophils purified from the peritoneal cavity of human serum-treated guinea pigs was investigated. Degranulation (eosinophil peroxidase, EPO), oxidative burst (O2-), [Ca2+]i mobilization, and arachidonic acid metabolism (thromboxane B2, TXB2) were used as indices of eosinophil activation. SP (100 nM to 100 microM), FMLP (1 to 100 microM) and melittin (10 nM to 100 microM) induced EPO release but only FMLP (1 to 100 microM) led to an elevation of [Ca2+]i. The melittin- and SP-induced EPO secretion occurred at both cytotoxic and noncytotoxic concentrations as assessed by lactate dehydrogenase release. In addition, the effect of SP was not inhibited by the SP analogue (D-Pro4, D-Trp7,9,10)SP(4-11) and SP failed to promote the generation and subsequent release of TXA2. In contrast, FMLP (10 to 100 microM) stimulated the release of TXB2 from guinea pig eosinophils that was selectively inhibited by pretreatment of the cells with BOC-FMLP. On an equimolar basis (1 microM), melittin was approximately fivefold more active at promoting TXB2 release than FMLP. The results indicate that eosinophils respond to the three peptides, SP, melittin, and FMLP in differential fashion. We conclude that activation of guinea pig eosinophils by FMLP is likely to be receptor-mediated whereas the actions of SP and melittin may act through nonspecific peptide-membrane phospholipid interactions. .A Kroegel C; Giembycz MA; Barnes PJ. .I 275694 .U 91010734 .S J Immunol 9101; 145(8):2588-94 .M Antigen p150,95/PH; Cell Adhesion/*/DE; Cell Adhesion Molecules/*PH; Cells, Cultured; Endothelium, Vascular/*CY; Granulocytes/*CY; Human; In Vitro; Lymphocyte Function-Associated Antigen-1/PH; Macrophage-1 Antigen/PH; Monocytes/*CY; Support, Non-U.S. Gov't; Tetradecanoylphorbol Acetate/PD. .T Distinct adhesive properties of granulocytes and monocytes to endothelial cells under static and stirred conditions. .P JOURNAL ARTICLE. .W Adherence of neutrophils and monocytes to endothelium is an important event in the sequence of leukocyte responses to inflammatory disease. Double-color flow microfluorimetry analysis was used to determine neutrophil and monocyte adherence to suspended endothelial cells under stirred conditions. The static adherence to endothelial cell monolayers was simultaneously determined. In both assays, neutrophils behaved in a similar way. Basal adherence of neutrophils was very low. Activation by PMA or by the chemoattractants platelet-activating factor and FMLP induced rapid binding, primarily mediated by CR3. Nonactivated neutrophils showed CD18-dependent (lymphocyte function-associated Ag-1 and CR3) and CD18-independent adherence to endothelial cells when the endothelial cells were prestimulated with rIL-1 beta. In contrast to neutrophils, nonactivated monocytes adhered avidly to resting endothelial cells. This adherence was partly CD18 dependent and partly CD18 independent. Whereas monocyte adherence under stirred conditions strongly increased upon activation by PMA, a significant decrease in adherence was found under static conditions, which was prevented by cytochalasin B. This decrease was limited to a distinct CD18-independent binding mechanism, and absent under stirred conditions. We conclude that monocytes adhere with (at least) three binding mechanisms to endothelial cells, a CD18-dependent and two CD18-independent mechanisms. .A Kuijpers TW; Hakkert BC; van Mourik JA; Roos D. .I 275695 .U 91010736 .S J Immunol 9101; 145(8):2602-7 .M Antibody Formation/*DE; B-Lymphocytes/CY/*IM/ME; Cell Division/DE; Cell Line; Cell Survival/DE; Dose-Response Relationship, Drug; Drug Administration Schedule; Human; In Vitro; Platelet Activating Factor/AI/ME/*PD; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Platelet-activating factor enhances Ig production in B lymphoblastoid cell lines. .P JOURNAL ARTICLE. .W Platelet-activating factor (PAF) is a highly potent phospholipid mediator known to be active in many biologic systems. To date, little is known of the effect of PAF on B lymphocytes. Using two Ig-secreting B lymphoblastoid cell lines, we have demonstrated that PAF can enhance Ig production by these cells in a dose-dependent fashion. PAF also causes significant alteration of the kinetics of Ig secretion in these lymphoblastoid cell lines. The effect of PAF is rapid, with detection of 6- to 12-fold increases in Ig production in the first 24 h of cell culture, followed by a plateau during the next 24 to 48 h. The specificity of the PAF effect on Ig secretion is emphasized by lyso-PAF having no Ig-enhancing properties and by the inhibition of Ig enhancement in the presence of the structural analogue PAF antagonist CV3988 and the soluble nonstructural analogue PAF receptor antagonist Web 2086. PAF does not cause an increase in the kinetics of cell proliferation or an increase in cell numbers at any time during a 72-h culture period. In an attempt to explain the increase in Ig secretion in the absence of changes in growth parameters, an ELISA spot assay for enumeration of Ig-secreting cells was developed. This assay demonstrated that the increase in Ig production is likely due to enhancement of single cell Ig secretion rather than an increase in cell number. These data indicate that PAF may have an important immunomodulatory role in the production of Ig by B lymphocytes. .A Mazer B; Clay KL; Renz H; Gelfand EW. .I 275696 .U 91010737 .S J Immunol 9101; 145(8):2608-15 .M Alkaloids/PD; Antibodies, Monoclonal; Antigens, CD/*PH; Cell Aggregation/DE; Cell Degranulation/DE; Diglycerides/PD; Dose-Response Relationship, Drug; Enzyme Activation; Human; In Vitro; Macrophage-1 Antigen/ME/*PH; N-Formylmethionine Leucyl-Phenylalanine/PD; Neutrophils/*CY; Phosphorylation; Protein Kinase C/AI/*PH; Receptors, Leukocyte-Adhesion/ME; Support, U.S. Gov't, P.H.S.; Tetradecanoylphorbol Acetate/PD. .T Two pathways of CD11b/CD18-mediated neutrophil aggregation with different involvement of protein kinase C-dependent phosphorylation. .P JOURNAL ARTICLE. .W The characteristics of homotypic neutrophil aggregation, mediated by the adhesion molecule CD11b/CD18, differ according to whether activation takes place via intracellular protein kinase C(PKC) inducers or chemoattractants. In response to diacylglycerol (DAG) analogues such as PMA and 1,2-dioctanoyl-sn-glycerol, a prolonged cellular aggregation occurs that is associated with intense phosphorylation of the CD18 beta-chain. In response to the chemoattractant FMLP, a more transient aggregation event results that is associated with minimal beta-chain phosphorylation. By using the PKC inhibitor staurosporine, we now show that these differences are likely to reflect two different pathways of activation. Both aggregation and phosphorylation induced by DAG analogues are completely abolished by staurosporine in a parallel dose-dependent manner. Conversely, FMLP-induced aggregation is enhanced and prolonged by staurosporine whereas the associated minimal phosphorylation event is further diminished by staurosporine. Accordingly, activation of neutrophil aggregation by DAG analogues is associated with and presumably due to phosphorylation of the CD18 beta-chain. This intense phosphorylation occurs via a staurosporine-sensitive kinase such as PKC. FMLP, on the other hand, appears to activate CD11b/CD18 by a distinct mechanism. This latter mechanism does not seem to be dependent on what may be a minor PKC-induced phosphorylation of the beta-chain, and indeed is enhanced by inhibition of PKC. Of note, staurosporine was also found to cause selective release of specific granules with concomitant increase in surface display of CD11b/CD18. These data further support previous observations that up-regulation of this adhesive molecule is not the primary event in the induction of cellular adhesiveness. .A Merrill JT; Slade SG; Weissmann G; Winchester R; Buyon JP. .I 275697 .U 91010738 .S J Immunol 9101; 145(8):2616-25 .M Adenosine Cyclic Monophosphate/PH; Antigens, CD/PH; Antigens, Differentiation, T-Lymphocyte/PH; Blotting, Northern; Cholera Toxin/PD; Dideoxyadenosine/PD; Dinoprostone/*PD; Forskolin/PD; Gene Expression/DE; Human; In Vitro; Interleukin-2/BI/*GE; Lymphocyte Transformation/*DE; Phytohemagglutinins/PD; Receptors, Antigen, T-Cell/PH; RNA, Messenger/GE; Support, U.S. Gov't, P.H.S.; T-Lymphocytes/*PH; Tetradecanoylphorbol Acetate/PD; Transcription, Genetic/DE; T4 Lymphocytes/PH. .T Delineation of the mechanism of inhibition of human T cell activation by PGE2. .P JOURNAL ARTICLE. .W The capacity of PGE2 to inhibit human T cell responses was examined by investigating its effect on mitogen-induced IL-2 production and proliferation of highly purified CD4+ T cells. PGE2 inhibited both PHA and anti-CD3 induced proliferation and IL-2 production by an action directly on the responding T cell. Inhibition of IL-2 production reflected decreased accumulation of mRNA for IL-2. A variety of other cAMP elevating agents exerted similar inhibitory effects. Inhibition of proliferation could be overcome by supplemental IL-2, PMA, or the anti-CD28 mAb 9.3. Although PMA and 9.3 markedly increased the amount of IL-2 produced by mitogen-stimulated T cells, the percentage inhibition of IL-2 secretion caused by PGE2 and other cAMP elevating agents remained comparable in these costimulated cultures. Rescue of T cell DNA synthesis by these agents appeared to reflect the finding that, although PGE2 markedly inhibited IL-2 production, the absolute amount of IL-2 produced was increased sufficiently to sustain mitogen-induced proliferation. As anticipated, PGE2, forskolin, and cholera toxin increased T cell cAMP levels. The quantity of cellular cAMP generated in response to PGE2, cholera toxin, and forskolin could be inhibited by PMA or 2',5'-dideoxyadenosine. Using these reagents, the inhibitory effects of PGE2 were found to reflect intracellular cAMP levels, but only within a very narrow range. The results indicate that by elevating cAMP levels, PGE2 inhibits human T cell IL-2 production at a point that is common to both the CD3 and CD28 signaling pathways. .A Minakuchi R; Wacholtz MC; Davis LS; Lipsky PE. .I 275698 .U 91010739 .S J Immunol 9101; 145(8):2626-32 .M Blood Proteins/*PH; Cell Degranulation; Cells, Cultured; Cytochalasin B/PD; Eosinophils/*PH; Flow Cytometry; Glucuronidase/ME; Human; In Vitro; Lactate Dehydrogenase/ME; Luminescence; Lysosomes/*EN; N-Formylmethionine Leucyl-Phenylalanine/PD; Neutrophils/*PH; Platelet Activating Factor/PD; Superoxide/*ME; Support, U.S. Gov't, P.H.S.. .T Noncytotoxic activation of neutrophils by eosinophil granule major basic protein. Effect on superoxide anion generation and lysosomal enzyme release. .P JOURNAL ARTICLE. .W Eosinophil granule major basic protein (MBP) and neutrophils have each been implicated in the inflammatory late phase events of allergic disease. Based on this association and flow cytometric evidence presented in this report for MBP binding to neutrophils, we examined the ability of MBP to activate human neutrophils. Incubation of neutrophils with 0.5 to 3.0 microM MBP at room temperature produced a concentration-dependent chemiluminescence (CL) response that peaked after 50 to 70 min. Reduced-and-alkylated MBP, eosinophil cationic protein, and eosinophil-derived neurotoxin did not induce CL. MBP-induced CL was abrogated in the absence of Ca2+ and was absent in neutrophils isolated from two individuals with chronic granulomatous disease. MBP also stimulated release of superoxide anion (O2-) and lysozyme but not beta-glucuronidase or lactate dehydrogenase. Additionally, 1.5 microM MBP in combination with FMLP or platelet-activating factor stimulated a synergistic increase in O2- release from cytochalasin B-treated neutrophils. The degree of synergism with FMLP or platelet-activating factor was inversely related (p less than 0.005) to the level of MBP-induced O2- release. These results indicate that MBP activates neutrophils in a noncytolytic fashion and provide evidence that eosinophil-neutrophil collaboration may contribute to the pathogenesis observed in allergic late phase reactions. .A Moy JN; Gleich GJ; Thomas LL. .I 275699 .U 91010740 .S J Immunol 9101; 145(8):2633-8 .M Animal; Cell Adhesion/DE; Cell Aggregation/DE; Cell Degranulation/DE; Complement 5a/PD; Inflammation/PP; Interleukin-1/PD; Interleukin-8/PD; Leukotrienes B/PD; N-Formylmethionine Leucyl-Phenylalanine/PD; Neutrophils/*PH; Pertussis Toxins/*PD; Rabbits; Receptors, Leukocyte-Adhesion/AN; Recombinant Proteins; Skin/CY; Support, Non-U.S. Gov't; Tetradecanoylphorbol Acetate/PD; Zymosan/PD. .T Evidence that a receptor-operated event on the neutrophil mediates neutrophil accumulation in vivo. Pretreatment of 111In-neutrophils with pertussis toxin in vitro inhibits their accumulation in vivo. .P JOURNAL ARTICLE. .W The role of neutrophil chemoattractant receptors in neutrophil stimulation in vitro is well established, however, the precise mechanisms underlying local neutrophil accumulation at inflammatory sites in vivo have not been defined. A fundamental question that remains open is whether chemoattractants act on the endothelial cell or the neutrophil to initiate the process of neutrophil migration in vivo. To address this question we have investigated whether neutrophil accumulation in vivo can occur if chemoattractant receptor occupancy is uncoupled from neutrophil stimulation. For this purpose we have used pertussis toxin (PT) as the pharmacologic tool. We have investigated the effect of in vitro pretreatment of rabbit neutrophils with PT on their responses in vitro and on their accumulation in vivo. Pretreatment of rabbit neutrophils with PT inhibited FMLP- and C5a-, but not PMA- induced increases in CD18 expression, neutrophil adherence, and degranulation in vitro. This pretreatment procedure with PT inhibited the accumulation of radiolabeled neutrophils in vivo in response to intradermally injected FMLP, C5a, C5a des Arg, leukotriene B4, IL-8, and zymosan in rabbit skin. Further, in contrast to the in vitro results, PT inhibited the PMA-induced 111In-neutrophil accumulation in vivo. Interestingly, pretreatment of neutrophils with PT also inhibited accumulation in response to intradermally injected IL-1, despite the reports that IL-1 lacks neutrophil chemoattractant activity in vitro. Although the experimental techniques used cannot distinguish the different stages of neutrophil migration involved, these results suggest that the accumulation of neutrophils induced by local extravascular chemoattractants in vivo depends on a pertussis toxin-sensitive receptor operated event on the neutrophil itself. Further, PMA and IL-1 may release secondary chemoattractants in vivo. .A Nourshargh S; Williams TJ. .I 275700 .U 91010741 .S J Immunol 9101; 145(8):2639-43 .M Animal; Chemotaxis, Leukocyte/*DE; Dose-Response Relationship, Drug; Human; In Vitro; Inflammation/PP; Mice; Mice, Inbred BALB C; Myeloperoxidase/ME; Neutrophils/*PH; Rabbits; Recombinant Proteins; Sepharose; Skin/CY; Time Factors; Tumor Necrosis Factor/*PD. .T Inhibition of neutrophil migration by tumor necrosis factor. Ex vivo and in vivo studies in comparison with in vitro effect. .P JOURNAL ARTICLE. .W Coincubation of neutrophils with TNF inhibited the chemoattractant-directed migration of neutrophils under agarose and enhanced their migration in the multiwell chemotaxis chamber. To assess the physiological significance of these differing in vitro TNF effects, ex vivo and in vivo investigations were performed using animal models. Neutrophils from the peripheral blood of rabbits preadministered systemic TNF showed impaired ability to migrate toward chemoattractants in vitro. In addition, systemic TNF administration suppressed zymosan-activated plasma-induced local accumulation of leukocytes in mouse skin. The results indicate that circulating TNF may act as a suppressor for local inflammatory reaction. .A Otsuka Y; Nagano K; Nagano K; Hori K; Oh-ishi J; Hayashi H; Watanabe N; Niitsu Y. .I 275701 .U 91010742 .S J Immunol 9101; 145(8):2644-51 .M Adenosine Cyclic Monophosphate/PH; Alprostadil/PD; Animal; B-Lymphocytes/*ME; Cholera Toxin/PD; Dinoprost/PD; Dinoprostone/*PD; IgE/*BI; IgG/*BI; IgM/BI; Immunoglobulin Isotypes/BI; Interleukin-4/*PD; Lymphocyte Transformation/DE; Male; Mice; Spleen/CY; Support, U.S. Gov't, P.H.S.. .T Prostaglandin E2 promotes IL-4-induced IgE and IgG1 synthesis. .P JOURNAL ARTICLE. .W PG of the E series are generally known to suppress immune responses, however, we have found that PGE synergizes with IL-4 to induce IgE and IgG1 production in LPS-stimulated murine B lymphocytes. PGE2 and PGE1 (10(-6) to 10(-8) M) significantly increase IgE and IgG1 production (up to 26-fold) at all concentrations of IL-4 tested. In addition to its effects on IgE and IgG1, PGE also causes a significant decrease in IgM and IgG3 synthesis, suggesting that PGE may promote IL-4-induced class switching. The specificity of the E series PG effect is demonstrated by the fact that PGF2 alpha (10(-6) M) does not alter production of any of these isotypes. Because PGE can mediate its effects through cAMP in some cases, we investigated the importance of cAMP levels in regulation of isotype expression. Other agents that increase intracellular cAMP levels (cholera toxin and dibutyryl cAMP) were assessed for their ability to regulate isotype differentiation. Cholera toxin (100 pg/ml) and dibutyryl cAMP (100 microM) significantly enhanced IgE and IgG1 production and diminished IgM and IgG3 synthesis. We also show that PGE and cholera toxin elevate intracellular cAMP in B lymphocytes in a dose-dependent manner. In contrast, PGF2 alpha (10(-6) M) and the B subunit of cholera toxin (100 pg/ml) did not increase cAMP and did not regulate the isotype of Ig produced, reiterating the importance of cAMP in enhancing isotype differentiation. Although PGE is known to inhibit a number of immune responses, our data show that it is not always inhibitory. PGE may play a role in atopy in vivo where PGE-secreting cells such as macrophages, follicular dendritic cells, and fibroblasts can promote IgE synthesis. This research emphasizes the importance of PGE in regulation of the humoral immune response and adds a new stimulatory action to the repertoire of known PGE effects. .A Roper RL; Conrad DH; Brown DM; Warner GL; Phipps RP. .I 275702 .U 91010743 .S J Immunol 9101; 145(8):2652-61 .M Amino Acid Sequence; Cathepsins/CH/IM/*ME; Electrophoresis, Polyacrylamide Gel; Human; Immunochemistry; Mast Cells/*EN; Molecular Sequence Data; Pancreatopeptidase/ME; Peptide Hydrolases/ME; Serine Proteinases/CH/ME; Support, U.S. Gov't, P.H.S.. .T Identification of a cathepsin G-like proteinase in the MCTC type of human mast cell. .P JOURNAL ARTICLE. .W Human mast cells can be divided into two subsets based on serine proteinase composition: a subset that contains the serine proteinases tryptase and chymase (MCTC), and a subset that contains only tryptase (MCT). In this study we examined both types of mast cells for two additional proteinases, cathepsin G and elastase, which are the major serine proteinases of neutrophils. Because human mast cell chymase and cathepsin G are both chymotrypsin-like proteinases, the properties of these enzymes were further defined to confirm their distinctiveness. Comparison of their N-terminal sequences showed 30% nonidentity over the first 35 amino acids, and comparison of their amino acid compositions demonstrated a marked difference in their Arg/Lys ratios, which was approximately 1 for chymase and 10 for cathepsin G. Endoglycosidase F treatment increased the electrophoretic mobility of chymase on SDS gels, indicating significant N-linked carbohydrate on chymase; no effect was observed on cathepsin G. Immunoprecipitation and immunoblotting with specific antisera to each proteinase revealed little, if any, detectable cross-reactivity. Immunocytochemical studies showed selective labelling of MCTC type mast cells by cathepsin G antiserum in sections of human skin, lung, and bowel. No labeling of mast cells by elastase antiserum was detected in the same tissues, or in dispersed mast cells from lung and skin. A protein cross-reactive with cathepsin G was identified in extracts of human skin mast cells by immunoblot analysis. This protein had a slightly higher Mr (30,000) than the predominant form of neutrophil cathepsin G (Mr 28,000), and could not be separated from chymase (Mr 30,000) by SDS gel electrophoresis because of the size similarity. Using casein, a protein substrate hydrolyzed at comparable rates by chymase and cathepsin G, it was shown that about 30% of the caseinolytic activity in mast cell extracts was sensitive to inhibitors of cathepsin G that had no effect on chymase. Hydrolytic activity characteristic of elastase was not detected in these extracts. These studies indicate that human MCTC mast cells may contain two different chymotrypsin-like proteinases: chymase and a proteinase more closely related to cathepsin G, both of which are undetectable in MCT mast cells. Neutrophil elastase, on the other hand, was not detected in human mast cells by our procedures. .A Schechter NM; Irani AM; Sprows JL; Abernethy J; Wintroub B; Schwartz LB. .I 275703 .U 91010745 .S J Immunol 9101; 145(8):2669-76 .M Cytopathogenic Effect, Viral; DNA, Viral/AN; Human; HIV/*GD; In Vitro; Interferon Type I/*PD; Macrophages/MI; Monocytes/*MI; Polymerase Chain Reaction; RNA, Messenger/ME; RNA, Viral/ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Time Factors; T4 Lymphocytes/MI; Virus Replication/*DE. .T Regulation of HIV replication in infected monocytes by IFN-alpha. Mechanisms for viral restriction. .P JOURNAL ARTICLE. .W In a survey of 15 different virus isolates, no IFN-alpha or IFN-beta activity was detected in culture fluids of HIV-infected T cells or monocytes. Exogenous rIFN-alpha added to T lymphoblast or monocyte cultures induced restriction in replication of the amphotropic HIV that infect both cell types. With IFN-treated HIV-infected T cells, levels of reverse transcriptase (RT) activity in culture fluids were half those in control cultures, but the frequency of infected cells or the levels of p24 Ag released in culture fluids were unchanged. In contrast to the modest effect of IFN on HIV-infected T cells, IFN-induced antiviral activity in monocytes was quite dramatic. Monocytes treated with IFN at the time of virus challenge showed no evidence of HIV infection: no p24 Ag or RT activity, no viral mRNA, and no proviral DNA. In this system, IFN interrupts one or more early event(s) in the virus replication cycle before formation of proviral DNA. Monocyte cultures infected with HIV 7 days before IFN treatment showed a gradual decrease in levels of p24 Ag and RT activity to baseline by 3 wk. HIV-induced cytopathic changes were markedly reduced, and the frequency of productively infected cells was less than or equal to 1% of total cells. Virus particles released 24 h after IFN treatment were 100- to 1000-fold less infectious than equal numbers of control virions. But, monocytes treated with IFN 7 days after HIV infection were not free of the retroviral pathogen: levels of proviral DNA in the IFN-treated and control HIV-infected cells were indistinguishable. The presence of large quantities of proviral DNA in cells with little or no evidence for active transcription documents a situation approaching true microbiological latency. .A Gendelman HE; Baca LM; Turpin J; Kalter DC; Hansen B; Orenstein JM; Dieffenbach CW; Friedman RM; Meltzer MS. .I 275704 .U 91010746 .S J Immunol 9101; 145(8):2677-85 .M Adjuvants, Immunologic; Amino Acid Sequence; Animal; Antigenic Determinants; B-Lymphocytes/IM; HIV Antibodies/*BI; HIV Antigens/CH/*IM; HIV Envelope Protein gp120/CH/*IM; Leukocyte Count; Lymphocyte Subsets/IM; Lymphocyte Transformation; Macaca mulatta; Molecular Sequence Data; Neutralization Tests; Peptides/CH/*IM; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; T-Lymphocytes/IM; Vaccines, Synthetic/IM. .T Synthetic peptides containing T and B cell epitopes from human immunodeficiency virus envelope gp120 induce anti-HIV proliferative responses and high titers of neutralizing antibodies in rhesus monkeys. .P JOURNAL ARTICLE. .W We have previously described a synthetic peptide (T1-SP10) derived from two noncontiguous regions of HTLVIIIB envelope gp120 (T1, amino acids 428-443; SP10, amino acids 303-321) that induced type-specific anti-HIV neutralizing antibodies and T cell proliferative responses against native HIV gp120 when used as a carrier-free immunogen in goats. In this study, HTLVIIIB T1-SP10 synthetic peptides were used to immunize rhesus monkeys to determine if the peptides were capable of eliciting HIV-specific neutralizing antibody and proliferative responses in primates. Four compounds (alum, polyA:polyU, threonyl-muramyldipeptide (MDP) and IFA) were also compared for efficacy as adjuvants in this system. Rhesus monkeys immunized with T1-SP10 peptides generated high titers of antibodies against the immunogens and also against HTLVIIIB gp120. Sera from all four animals given T1-SP10 in IFA or threonyl-MDP neutralized infection by HTLVIIIB and blocked virus-dependent cell fusion events. A peak neutralization titer of 1:940 was seen in one animal given IFA (19600) and a titer of 1:900 was seen in one of the monkeys (17371) given threonyl-MDP. Proliferative responses of immune rhesus PBMC to T1-SP10 appeared after the first injection. After eight immunizations, two of eight monkeys (one injected with peptides in threonyl-MDP and one given peptides in IFA) had PBMC proliferative responses to native HTLVIIIB gp120. These data demonstrate that the carrier-free T1-SP10 synthetic peptide construct can induce high titers of neutralizing anti-HIV antibody responses and PBMC proliferative responses to HIV in primates. .A Hart MK; Palker TJ; Matthews TJ; Langlois AJ; Lerche NW; Martin ME; Scearce RM; McDanal C; Bolognesi DP; Haynes BF. .I 275705 .U 91010748 .S J Immunol 9101; 145(8):2691-6 .M Amino Acid Sequence; Animal; Antibodies, Protozoan/*IM; Antigens, Protozoan/*IM; Antigens, Surface/IM; Mice; Mice, Inbred Strains; Molecular Sequence Data; Peptides/CH/IM; Plasmodium falciparum/*IM; Protozoan Proteins/CH/*IM; Support, Non-U.S. Gov't. .T Synthetic peptide immunogens eliciting antibodies to Plasmodium falciparum sporozoite and merozoite surface antigens in H-2b and H-2k mice. .P JOURNAL ARTICLE. .W Peptides representing conserved (MSA2/1A and MSA2/1B) and variant (MSA2/2, MSA2/6 and MSA2/7) regions of the merozoite surface Ag 2 (MSA2) of Plasmodium falciparum (FCQ-27/PNG isolate) were coupled to either peptide NP(NANP)5NA or peptide C(NANP)6 both of which contained the core sequence (NANP)n. The coupling was done via the N-terminus of one peptide and a cysteine residue on either terminus of the other. BL/10 (H-2b) and B10.BR (H-2k) mice were immunized with these MSA2-(NANP)n conjugates. The mice were also immunized with the unconjugated MSA2 peptides and with NP(NANP)5NA and C(NANP)6. Antibody responses were evaluated by 1) ELISA, in which the MSA2 peptides and C(NANP)6 were used as Ag; 2) immunofluorescence assays (IFAT) against intact sporozoites and merozoites; and 3) immunoblotting experiments against solubilized P. falciparum blood stage proteins. High titer antibodies to (NANP)n were elicited in both BL/10 and B10.BR mice after immunization with all the conjugates except MSA2/7-(NANP)n which gave only a very limited response in B10.BR mice. These antibodies recognized unfixed sporozoites. The conjugates also elicited antibodies to MSA2 as shown by ELISA, IFAT, and immunoblotting except for mice immunized with MSA2/1B-(NANP)n where an anti-MSA2 response was only detectable by immunoblotting. Immunization with unconjugated MSA2 peptides showed that MSA2/2 was immunogenic in both BL/10 and BR.10 mice, with MSA2/6 and MSA2/7 being immunogenic only in BL/10 mice. The antibodies elicited recognized both merozoites and the MSA2 protein. However, the antibody titers were lower overall than those seen when these peptides were used in the conjugated form. No anti-MSA2 antibodies were detected after immunization with MSA2/1A and MSA2/1B. Immunization of mice with the peptide NP(NANP)5NA produced antibodies in BL/10 (H-2b) mice only, and the immunogenicity of this preparation was poor. In contrast, C(NANP)6 produced a strong antibody response in both mouse strains. The antibodies elicited by NP(NANP)5NA and C(NANP)6 recognised sporozoites in IFAT. The MSA2 peptides studied (or their derivatives) were previously shown to be recognized by human T cells. Their immunogenic potential shows promise in that complex anti-P. falciparum responses can be elicited with simple synthetic immunogens based on these peptides. .A Rzepczyk CM; Csurhes PA; Lord R; Matile H. .I 275706 .U 91010755 .S J Immunol 9101; 145(8):2730-6 .M Amino Acid Sequence; B-Lymphocytes/*IM/ME; Base Sequence; Blotting, Northern; Cell Compartmentation; Cell Line; Cloning, Molecular; DNA/GE; Electrophoresis, Gel, Two-Dimensional; Gene Expression; Human; HLA-DR Antigens/*ME; In Vitro; Molecular Sequence Data; Monensin/PD; Mutation; Support, U.S. Gov't, P.H.S.. .T Rapid nonlysosomal degradation of assembled HLA class II glycoproteins incorporating a mutant DR alpha-chain. .P JOURNAL ARTICLE. .W Gamma irradiation followed by antibody and complement selection was used to isolate a human B-lymphoblastoid cell line that no longer expresses HLA-DR molecules on its cell surface. Cell surface expression in the mutant (HMy2.DRN) was restored by transfecting a wildtype DRA but not a DRB cDNA, suggesting that a structural mutation in the DRA mRNA or protein was responsible for the lack of cell surface expression. Nucleotide sequence analysis of the DRA mRNA from HMy2.DRN revealed a 75 nucleotide deletion corresponding to the start of the alpha 2 domain and involving one of two cysteines that are involved in the formation of an intrachain disulfide bond. At the biochemical level, only minute quantities of HLA-DR could be precipitated from this cell line after a 4-h continuous label with 35S-methionine. HLA-DR beta and the class II-associated invariant chain could be seen coprecipitating with the mutant DR alpha-chain, suggesting a limited accumulation of normally assembled molecules. However, by carrying out the labeling at 16 degrees C instead of 37 degrees C, equivalent amounts of HLA-DR could be precipitated from parent and mutant alike. The mutant DR alpha chain was found in association with the beta-chain, but with reduced association with the invariant chain under these conditions. Pulse chase analysis in the parent and mutant cell lines indicated that this mutant DR alpha beta I complex undergoes a process of degradation at 37 degrees C. Inhibitors of intracellular transport such as monensin were ineffective in blocking this process of degradation. This work is consistent with published reports implicating the involvement of a pre-Golgi or an early Golgi compartment in the proteolysis of aberrantly folded or assembled multisubunit proteins. .A Koppelman B; Cresswell P. .I 275707 .U 91010756 .S J Immunol 9101; 145(8):2737-44 .M Amino Acid Sequence; Base Sequence; Chemotactic Factors/*GE; Chromosomes, Human, Pair 17/*; Cloning, Molecular; Comparative Study; Cytokines/*GE; Genes, Reiterated; Genes, Structural/*; Human; Molecular Sequence Data; Regulatory Sequences, Nucleic Acid; Support, U.S. Gov't, Non-P.H.S.; Transcription, Genetic. .T Sequence and chromosomal location of the I-309 gene. Relationship to genes encoding a family of inflammatory cytokines. .P JOURNAL ARTICLE. .W We previously reported the isolation and characterization of a cDNA clone, I-309, that encodes a small secreted protein produced by activated human T lymphocytes. This protein is structurally related to a large number of recently identified proteins that are secreted upon cellular activation. In this report we describe the isolation and characterization of the gene encoding I-309. The genomic organization is essentially identical to that found in the genes encoding the structurally similar proteins TCA-3, hJE/MCP-1, and mJE, strengthening the hypothesis that these genes are evolutionarily related. The region of the I-309 gene 5' of the mRNA cap site exhibits extensive nucleotide sequence homology with the same region of the murine gene TCA-3, providing additional evidence that I-309 and TCA-3 are likely to be homologs. Finally, panels of rodent-human somatic cell hybrids were used to map the I-309 gene to human chromosome 17. In conjunction with recent mapping data from other laboratories, this result suggests the presence of a cluster of related genes on this chromosome. .A Miller MD; Wilson SD; Dorf ME; Seuanez HN; O'Brien SJ; Krangel MS. .I 275708 .U 91010757 .S J Immunol 9101; 145(8):2745-50 .M Animal; Cells, Cultured; Chemotactic Factors/*GE; Cloning, Molecular; Cytokines/*GE; Gene Expression; Glycoproteins/*GE; Glycosylation; In Vitro; Inflammation/PP; Mice; Molecular Weight; Protein Processing, Post-Translational; Recombinant Proteins; Transfection. .T Expression and characterization of TCA3: a murine inflammatory protein. .P JOURNAL ARTICLE. .W TCA3 is a cDNA originally isolated from activated T cells. Transcription of this gene has been shown to correlate with Ag-induced cellular activation of both T cells and mast cells. Based on the predicted amino acid sequence encoded by the cDNA, we previously proposed that TCA3 represents a cytokine. In this report we have used rDNA technology to express TCA3 in two mammalian cell lines. In both cases, TCA3 was expressed as a secreted molecule with an apparent molecular mass of 16 kDa. Digestion of the (rTCA3) with the enzyme N-glycanase revealed that approximately 8 kDa is caused by N-linked glycosylation. Intradermal injection of rTCA3 into mouse footpads resulted in a rapid swelling response. The sites of injection were characterized histologically by a local accumulation of neutrophils. These findings are discussed with particular attention to a family of related proteins, some of whose members also have inflammatory properties. .A Wilson SD; Kuchroo VK; Israel DI; Dorf ME. .I 275709 .U 91010759 .S J Immunol 9101; 145(8):2758-65 .M Adenocarcinoma/IM; Animal; Antibodies, Anti-Idiotypic/*IM; Antibodies, Monoclonal/*IM; Antibodies, Neoplasm/*IM; Antibody Specificity; Antigenic Determinants; Binding, Competitive; Blotting, Western; Carcinoembryonic Antigen/*IM; Colonic Neoplasms/IM; Human; Immunoenzyme Techniques; Immunoglobulin Idiotypes/IM; In Vitro; Mice; Support, U.S. Gov't, P.H.S.. .T Murine monoclonal anti-idiotype antibody as a potential network antigen for human carcinoembryonic antigen. .P JOURNAL ARTICLE. .W Carcinomas of the gastrointestinal tract are not curable by standard therapies. Thus, new therapeutic approaches for this disease are needed. This study proposes the use of anti-Id mAb as Ag substitutes to induce anti-tumor immunity in gastrointestinal cancer patients. Recently, we have generated and characterized one monoclonal anti-Id antibody, designated 3H1 (Ab2), which mimics biologically and antigenically a distinct and specific epitope of the 180,000 m.w. carcinoembryonic antigen (CEA) primarily expressed in high density by human pancreatic and colonic tumor cells. This epitope is unique to CEA and not present on other CEA-related lower m.w. members of the Ag family also found on normal tissues. The antigenic determinant as defined by the mAb 8019 (Ab1) against which the Ab2, 3H1 was raised, is absent on normal adult tissues by immunoperoxidase staining and haematopoietic cells including granulocytes by flow cytometry analysis. Anti-Id (Ab2) 3H1 induced CEA-specific antibodies in mice and rabbits. The immune sera from both mice and rabbits competed with Ab1 for binding to the colon carcinoma cell line LS174T and inhibited the binding of radioiodinated Ab1 to Ab2. This indicates that anti-anti-Id (Ab3) in mice and rabbits share idiotopes with Ab1 (8019). Furthermore, monoclonal Ab3 that bind to CEA have been generated from mice immunized with 3H1. The Ab3 (both polyclonal as well as monoclonal) immunoprecipitated the same 180,000 m.w. CEA as Ab1 (8019) by Western blotting analysis and showed almost identical immuno-staining patterns as Ab1 on colonic adenocarcinoma tissue sections from several patients. Collectively these data suggest that Ab2 3H1 could potentially be used clinically as a network Ag for immunotherapy of patients with CEA positive tumors. .A Bhattacharya-Chatterjee M; Mukerjee S; Biddle W; Foon KA; Kohler H. .I 275710 .U 91010760 .S J Immunol 9101; 145(8):2766-71 .M Animal; Antineoplastic Agents/*; Ascites; Exotoxins/*AD; Injections, Intraperitoneal; Interleukin-2/*AD; Mice; Mice, Inbred C57BL; Mice, Nude; Neoplasm Transplantation; Neoplasms, Experimental/*TH; Receptors, Interleukin-2/*ME; Recombinant Proteins; Survival Analysis. .T IL-2-PE40 prevents the development of tumors in mice injected with IL-2 receptor expressing EL4 transfectant tumor cells. .P JOURNAL ARTICLE. .W A number of different immunotherapeutic reagents are currently being developed to target IL-2R for the treatment of leukemia, graft rejection, and certain autoimmune diseases. Previously, we have shown that IL-2-PE40, a chimeric protein composed of human IL-2 linked to the N-terminus of a truncated form of Pseudomonas exotoxin (PE), could effectively kill a variety of cell lines in vitro expressing either low, intermediate, or high affinity IL-2R. Here, we demonstrate that IL-2-PE40 can successfully retard or prevent the growth of a lethal ascites tumor or a solid tumor composed of EL4J murine thymoma cells transfected with the p55 murine IL-2R. The transfected line, EL4J-3.4, expresses 1,000 to 3,000 high affinity IL-2R. Survival extension in the ascites model was achieved by initiating treatment either after 4 to 6 h or within 5 days post-tumor injection in both athymic nude and C57BL/6 mice. Similarly, the growth of an aggressive s.c. solid tumor could also be inhibited. Extension of survival was not achieved either by using the truncated toxin alone not attached to IL-2 or by using an IL-2-PE40Asp553 mutant lacking a functional toxin. Survival extension was not caused by IL-2 activated NK or other host effector mechanisms as IL-2-PE40 was unable to prevent the receptor-negative EL4J parental line from forming a lethal ascites or a solid tumor. Thus, IL-2-PE40 is a potent, specific cytolytic reagent that may prove useful in the arsenal of anti-IL-2R immunotherapeutics. .A Kozak RW; Lorberboum-Galski H; Jones L; Puri RK; Willingham MC; Malek T; Fitzgerald DJ; Waldmann TA; Pastan I. .I 275711 .U 91010761 .S J Immunol 9101; 145(8):2772-3 .M Animal; B-Lymphocytes/*IM; Haemophilus influenzae/*IM; Lymphocyte Transformation/*; Mice; Mice, Inbred Strains; Polysaccharides, Bacterial/*PD. .T Capsular polysaccharide of Haemophilus influenzae type b (Hib PS) is a mitogen for murine B cells [letter; comment] .P COMMENT; LETTER. .A Shin HS; Stein KE. .I 275712 .U 91010762 .S J Immunol 9101; 145(9):2779-90 .M Animal; B-Lymphocytes/*CY; Human; Immunologic Memory/*; Lectins/ME; Lymphocyte Transformation; Lymphoid Tissue/*CY; Mice; Research Support; Societies, Scientific; Stem Cells; Support, U.S. Gov't, P.H.S.; T-Lymphocytes/PH; United States. .T Focusing: the dilemma of interpreting sharp images on a blurred background. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .A Thorbecke GJ. .I 275713 .U 91010763 .S J Immunol 9101; 145(9):2791-6 .M Administration, Topical; Animal; Epidermis/*IM; Flow Cytometry; Haptens/*AD; Histocompatibility Antigens Class II/*ME; Langerhans Cells/*IM; Lymphocyte Transformation; Mice; Mice, Inbred Strains; Picryl Chloride/IM; T-Lymphocytes/IM; Time Factors. .T Phenotypic and functional characteristics of in vivo-activated Langerhans cells. .P JOURNAL ARTICLE. .W After short term culture (2 to 3 days), Langerhans cells (LC) exhibit increased class II MHC Ag and become more potent APC than freshly obtained LC in primary allogeneic and syngeneic T cell activation. To determine whether in vivo LC undergo changes similar to cultured LC, we examined the phenotypic and functional characteristics of LC harvested from ear skin of naive mice painted with various haptens and primary irritants. At 24 h after application of 3% trinitrochlorobenzene, LC appear larger and exhibit more intense staining in epidermal sheets using anti-I-A antibodies, and there was a two- to threefold increase in I-A and I-E expression by LC using flow microfluorimetry analysis. CD45 Ag expression was not altered. Flow microfluorimetry profiles showed the presence of two different LC populations based on fluorescence intensity, i.e., one with the same Ia density as nontreated LC and the other (representing 22 to 50% of all LC) with a markedly enhanced Ia density, (i.e., a 10-fold increase in I-A and I-E). This phenotypic change was observed only with haptens, such as trinitrochlorobenzene, dinitrofluorobenzene, oxazolone, and cinnamic aldehyde. In contrast, application of 10 to 30% sodium lauryl sulfate or vehicle controls did not induce this change. Functionally, LC obtained from hapten-painted mice induced a two- to fivefold increase in 3[H]-TdR incorporation by syngeneic or allogeneic T cells, compared to equal numbers of LC from nontreated or vehicle-treated or sodium lauryl sulfate-treated mice. These phenotypic and functional changes that occur in vivo are therefore analogous to those seen when LC are cultured for short periods of time. Thus, activated LC appear in vivo in response to the epicutaneous application of haptens and may represent an essential step in hapten-specific sensitization. .A Aiba S; Katz SI. .I 275714 .U 91010765 .S J Immunol 9101; 145(9):2803-8 .M Animal; Antigen-Presenting Cells/*IM; Antigens, Differentiation/AN; B-Lymphocytes/IM; Clone Cells; Helper Cells/*IM; Interleukin-1/PH; Interleukin-2/*BI; Interleukin-4/*BI; Lymphocyte Transformation; Mice; Mice, Inbred Strains; Receptors, Immunologic/PH; Support, U.S. Gov't, P.H.S.; T-Lymphocyte Subsets/IM; T4 Lymphocytes/*IM. .T Heterogeneity of helper/inducer T lymphocytes. III. Responses of IL-2- and IL-4-producing (Th1 and Th2) clones to antigens presented by different accessory cells. .P JOURNAL ARTICLE. .W Murine CD4+ T cell clones have been classified into at least two subsets, Th1 and Th2, on the basis of their distinct lymphokine secretion profiles and functions. In the present study, we compared the functional responses of Th1 and Th2 clones to Ag presentation by splenic B cells and peritoneal macrophages. Th2 clones secreted IL-4 in response to Ag presented by resting B cells, but their optimal proliferation required the addition of IL-1 or a source of IL-1. The degree of IL-1 dependence varied among the four Th2 clones examined. In contrast, Th1 clones secreted IL-2 and proliferated in response to Ag presented by both B cells and macrophages, without any requirement for exogenous IL-1. Furthermore, the proliferation of Th2 clones in response to Ag presented by splenocytes or macrophages was inhibited by an IL-1R antagonist. These results indicate that IL-1 is an important costimulator for the expansion of the Th2 subset of CD4+ T cells. The different requirements for the proliferation of Th1 and Th2 cells may be responsible for the preferential expansion of one or the other subset under different conditions of immunization. .A Chang TL; Shea CM; Urioste S; Thompson RC; Boom WH; Abbas AK. .I 275715 .U 91010767 .S J Immunol 9101; 145(9):2820-6 .M Animal; Antigen-Presenting Cells/CY/IM; Antigens, Surface/AN; Cell Compartmentation; Cells, Cultured; Comparative Study; Dendritic Cells/*CY/IM; Endocytosis; Epidermis/*CY/IM; Flow Cytometry; Histocompatibility Antigens Class II/ME; Hydrogen-Ion Concentration; Langerhans Cells/*CY/IM; Mice; Mice, Inbred Strains; Spleen/*CY/IM; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Freshly isolated spleen dendritic cells and epidermal Langerhans cells undergo similar phenotypic and functional changes during short-term culture. .P JOURNAL ARTICLE. .W Spleen dendritic cells (DC) and epidermal Langerhans cells (LC) belong to the same family of dendritic leukocytes and are considered to be prototypes of lymphoid DC and nonlymphoid DC, respectively. These cells are active APC in vitro and play a key role in the induction of primary T cell dependent immune responses in vivo. Two functional states of LC have been characterized in vitro, freshly isolated LC and cultured LC (cLC). That cLC closely resemble spleen DC in phenotype and function, has led to the hypothesis that LC undergo maturation toward DC while in culture, an event that has been correlated with the emigration of LC from skin into lymphoid organs. To date, however, DC have been studied only after overnight culture. To better understand the relationship between LC and DC, we examined DC shortly after their isolation from spleen, and after 24 h of culture. Freshly isolated DC (fDC) express high levels of MHC molecules and low levels of Fc gamma RII and C3biR; fDC also uniformly express the Ag recognized by the mAb 33D1, NLDC-145, and J11d. After culture, DC display a marked increase in the expression of MHC molecules, and they are induced to express the low affinity receptor for IL-2. By contrast, the expression of Fc gamma RII and F4/80 decreases with culture. With respect to function, fDC can efficiently present keyhole limpet hemocyanin to Ag-specific T cells, whereas cultured DC exhibit a marked reduction in this capacity. Finally, both fDC and cultured DC are capable of endocytosing surface Ia molecules, but only fDC are able to deliver them into acidic compartments. Our data indicate that fDC from spleen resemble freshly isolated LC from epidermis and that both cells undergo parallel changes during culture. These results suggest that LC and DC possess analogous attributes in vivo and respond similarly to external influences. .A Girolomoni G; Simon JC; Bergstresser PR; Cruz PD Jr. .I 275716 .U 91010769 .S J Immunol 9101; 145(9):2833-8 .M Animal; Antigen-Presenting Cells/*IM/PH; Cell Movement; Cell Separation; Dermatitis, Contact/*IM; Flow Cytometry; Langerhans Cells/IM/UL; Lymph Nodes/*CY/IM; Major Histocompatibility Complex; Mice; Mice, Inbred Strains; Microscopy, Electron; Skin/*IM; Support, U.S. Gov't, P.H.S.. .T Evidence that cutaneous antigen-presenting cells migrate to regional lymph nodes during contact sensitization. .P JOURNAL ARTICLE. .W These studies address the hypothesis that Ag-bearing epidermal Langerhans cells migrate to the regional lymph node during contact sensitization and function as APC. Skin from C3H mice was grafted onto BALB/c nude mice, and 7 or 14 days later, the recipients were sensitized with FITC through the grafts. APC from lymph nodes draining the site of sensitization were capable of sensitizing C3H recipients to FITC. Because sensitization is MHC restricted, only cells reaching the lymph node from the grafted skin could have induced contact hypersensitivity in C3H mice. Examination of the FITC+ draining lymph node cells by immunofluorescence and immunoelectron microscopy demonstrated that all were Ia+, most were F4/80+, and some contained Birbeck granules. These studies demonstrate that Ia+, FITC+ cells from the skin, at least some of which are Langerhans cells, leave the skin after epicutaneous sensitization with FITC and participate in the initiation of the contact hypersensitivity response within the regional lymph node. .A Kripke ML; Munn CG; Jeevan A; Tang JM; Bucana C. .I 275717 .U 91010770 .S J Immunol 9101; 145(9):2839-45 .M Antibodies, Monoclonal/ME; Antigenic Determinants; Antigens, CD/*IM; Antigens, CD4/*IM/ME/UL; Binding, Competitive; Human; HIV Envelope Protein gp120/ME; HLA-D Antigens/*IM; In Vitro; Lymphocyte Transformation/*; Major Histocompatibility Complex; Support, Non-U.S. Gov't; T4 Lymphocytes/*IM. .T Functional epitope analysis of the human CD4 molecule. The MHC class II-dependent activation of resting T cells is inhibited by monoclonal antibodies to CD4 regardless whether or not they recognize epitopes involved in the binding of MHC class II or HIV gp120. .P JOURNAL ARTICLE. .W This study was designed to define regions on the human CD4 molecule important for the class II-dependent activation of resting, polyclonal CD4 T cells. With the use of mAb to known epitopes on CD4, we assayed the degree of CD4 saturation and functional effects on T cell activation over a range of antibody concentrations in parallel titration experiments. This approach allows a quantitative comparison of different reagents, regardless of parameters such as affinity for CD4. In sharp contrast to results reported for preactivated T cells and CD4 transfected T cell hybridomas, all 22 CD4 mAb tested did inhibit proliferative responses of freshly isolated CD4 T cells to MHC class II Ag. At the lowest saturating concentration of each antibody, T cell proliferation was reduced by 45 to 82%. Inhibition did not depend on antibody-induced modulation of CD4 expression. Strikingly, no correlation was found between the functional effects and the specificity of the mAb for different epitopes on CD4, such as the putative binding sites for MHC class II or HIV glycoprotein gp120. .A Merkenschlager M; Buck D; Beverley PC; Sattentau QJ. .I 275718 .U 91010772 .S J Immunol 9101; 145(9):2854-61 .M Antibody Formation; Antigen-Presenting Cells/IM; Antigens, Differentiation/AN; Cell Separation; Epidermis/*IM/RE; Histocompatibility Antigens/AN; Human; Immune Tolerance/*; In Vitro; Langerhans Cells/IM; Lymphocyte Transformation; Major Histocompatibility Complex; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Suppressor Cells/*IM; T-Lymphocyte Subsets/IM; T4 Lymphocytes/*IM; Ultraviolet Rays. .T In vivo ultraviolet-exposed human epidermal cells activate T suppressor cell pathways that involve CD4+CD45RA+ suppressor-inducer T cells. .P JOURNAL ARTICLE. .W In vivo UV exposure of human epidermis abrogates the function of CD1+DR+ Langerhans cells and induces the appearance of CD1-DR+ Ag-presenting macrophages. Epidermal cells from UV-exposed skin, in contrast to epidermal cells from normal skin, potently activate autologous CD4+ T cells, and, in particular, the CD45RA+ (2H4+) (suppressor-inducer) subset. We therefore determined whether UV-exposure in humans leads to a T cell response in which suppression dominates. Autologous blood T cells were incubated with epidermal cell suspensions from in vivo UV-irradiated skin. After activation, repurified T cells were transferred in graded numbers to autologous mononuclear cells (MNC) stimulated with PWM and the resultant IgG production analyzed by ELISA. Relative to T cells activated by unirradiated control epidermal cells, T cells activated by UV-exposed epidermal cells demonstrated enhanced capacity to suppress IgG production (n = 6; p less than or equal to 0.03). Within the T cell population, CD8+ cells stimulated by UV-exposed epidermal cells could be directly activated to suppress PWM-stimulated MNC Ig production if IL-2 was provided in the reaction mixture. The suppressive activity was also transferable with purified CD4+ T cells stimulated by UV-exposed epidermal cells (n = 10; p less than or equal to 0.01), and was radiosensitive. Suppression was decreased when PWM-stimulated MNC were depleted of CD8+ T cells before mixing with CD4+ T cells activated by UV-exposed epidermal cells, suggesting indirect induction of CD8+ Ts cells contained within the responding MNC populations. Indeed, physical depletion of CD45RA+ cells resulted in total abrogation of the suppressor function contained in the CD4+ T cells. Activation of suppressor function was critically dependent on DR+ APC contained in UV-exposed epidermis. The data suggest that UV-exposure modulates cutaneous APC activity in humans, as in mice, such that the dominant immune response is tilted toward suppression. These mechanisms in normal individuals may function to dampen responses to UV-induced endogenous Ag that are pathogenic in autoimmune disorders. However, these mechanisms might also facilitate the growth of UV-induced skin cancers. .A Baadsgaard O; Salvo B; Mannie A; Dass B; Fox DA; Cooper KD. .I 275719 .U 91010773 .S J Immunol 9101; 145(9):2862-72 .M Animal; Antibodies, Monoclonal; Antigens, Differentiation, T-Lymphocyte/*PH; Autoimmune Diseases/GE/*IM; Calcium/*PH; Concanavalin A/PD; Inositol Phosphates/*PH; Interleukin-2/PD; Lymphocyte Transformation; Mice; Mice, Mutant Strains; Phospholipase C/ME; Receptors, Antigen, T-Cell/*PH; Signal Transduction; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; T-Lymphocyte Subsets/*PH; Tetradecanoylphorbol Acetate/PD; Time Factors; T4 Lymphocytes/PH. .T Intact antigen receptor-mediated generation of inositol phosphates and increased intracellular calcium in CD4 CD8 T lymphocytes from MRL lpr mice. .P JOURNAL ARTICLE. .W The predominant T lymphocytes that accumulate in the peripheral lymphoid tissues of mice homozygous for the lpr gene bear the phenotype CD3+CD4-CD8-. By certain functional criteria these cells would appear to have impaired CD3-mediated signal transduction, in that they do not respond to alloantigen and produce little if any detectable IL-2 or other lymphokines. However, the signal pathway appears adequate for achieving other T cell functions, including induction of high affinity IL-2R, and thymic deletion. To clarify the basis of this seeming discrepancy, we examined transmembrane signal transduction in T cell subsets of lpr/lpr (lpr) and +/+ mice, as defined by increased [Ca2+]i and the generation of inositol phosphates (InsPs). Stimulation of lpr CD4-CD8- cells with anti-CD3 antibody produced prompt and sustained increases in the concentration of [C2+]i and in InsPs. Similar responses occurred in mature T cells from lpr and +/+ mice, except for the somewhat slower kinetics of their increased [Ca2+]i. In marked distinction to the anti-CD2-mediated response, Con A, even in high doses, could not stimulate any increase of [Ca2+]i in lpr CD4-CD8- cells, and only modest increases in InsPs. Mature T cells, whether of lpr or +/+ origin, yielded normal increased [Ca2+]i with Con A. The reason for the differences in signal transduction between anti-CD3 and Con A stimulation of lpr CD4-CD8- cells may relate to the absence of surface structures on these immature T cells that are required for activation by Con A but not by anti-CD3. The data demonstrate that the CD3 complex in lpr CD4-CD8- T cells can couple to phospholipase C to hydrolyze phosphoinositides. These activation properties of lpr CD4-CD8- T cells have interesting functional parallels to thymocytes at the time of thymic selection, as well as tolerance induction of mature T lymphocytes. .A Budd RC; Winslow G; Inokuchi S; Imboden JB. .I 275720 .U 91010774 .S J Immunol 9101; 145(9):2873-9 .M Antigens, CD/*AN; Antigens, Surface/AN; B-Lymphocytes/*IM; Cell Differentiation; Flow Cytometry; Human; HLA-DR Antigens/*AN; Immunoglobulins, Surface/*AN; Immunologic Deficiency Syndromes/*IM; Infant; Infant, Newborn; Interleukin-2/PD; Interleukin-6/PD; Lymphocyte Transformation; Receptors, Transferrin/ME; Support, Non-U.S. Gov't. .T Human severe combined immunodeficiency disease: phenotypic and functional characteristics of peripheral B lymphocytes. .P JOURNAL ARTICLE. .W Human severe combined immunodeficiency disease (SCID) includes an X-chromosome-linked type characterized by a complete absence of mature T cells, hypogammaglobulinemia but normal or elevated number of B cells, suggesting that the disease results from a block in early T cell differentiation. It has been shown that B cells from obligate carrier women of this disorder exhibit the preferential use of the nonmutant X chromosome as the active X (as shown for T cells), suggesting that the SCID gene product has a direct effect on B cells as well as on T cells. To examine this question, we analyzed the phenotypic and functional characteristics of peripheral B cells from nine infants with SCID. We found a constant absence of spontaneously expressed activation Ag on B cell membrane from all SCID patients tested which contrasts with the phenotypic pattern exhibited by age-matched infants whom all cells bearing surface Ig express the 4F2 Ag and to a lesser extent the transferrin receptor. Concurrently, B cells from SCID patients have a profound impairment in their responses to stimuli that induce in vitro B cell proliferation and differentiation. Although rIL-2 and low-Mr B cell growth factor are potent inducers of proliferation on age-matched infants' B cells, they are poorly efficient in inducing proliferation of anti-mu-activated SCID B cells. This impairment is not related to the resting B cell phenotype of SCID B cells as shown by comparison with normal resting B cells. Furthermore, we observed an apparent block in B cell differentiation inasmuch as neither rIL-2 nor rIL-6 could support SAC-activated SCID B cell differentiation, both lymphokines being very efficient in inducing SAC-activated age-matched infants' B cell or purified resting B cell differentiation. These results suggest that the SCID gene defect has a direct effect on B cells and is required during B cell maturation. .A Gougeon ML; Drean G; Le Deist F; Dousseau M; Fevrier M; Diu A; Theze J; Griscelli C; Fischer A. .I 275721 .U 91010775 .S J Immunol 9101; 145(9):2880-5 .M Animal; Antigenic Determinants; Autoantigens/IM; Cell Adhesion Molecules/ME; Cell Line; Cytotoxicity, Immunologic/*; Encephalitogenic Basic Proteins/*IM; Haplotypes; Human; HLA-DR2 Antigen/*IM; In Vitro; L Cells; Lymphocyte Transformation; Mice; T-Lymphocytes, Cytotoxic/*IM; Transfection. .T HLA-DR2a is the dominant restriction molecule for the cytotoxic T cell response to myelin basic protein in DR2Dw2 individuals. .P JOURNAL ARTICLE. .W The HLA-DR2 restriction of the T cell response to myelin basic protein (MBP) was studied using murine L cells transfected with DRalpha and either DR2a or DR2b beta-chain cDNA. DR2a and DR2b represent the two isotypic DRbeta chains expressed in DR2Dw2 haplotypes. Eleven MBP-specific cytolytic T cell lines derived from patients with multiple sclerosis were isolated. Two of these cell lines recognized MBP-pulsed DR2-expressing L cell transfectants and four of them could only recognize the L cells if the adhesion molecule ICAM-1 was expressed in addition to HLA-DR2. Five of the six lines were restricted by HLA-DR2a; one line recognized Ag in conjunction with DR2b, but only if ICAM-1 was coexpressed. The remaining five lines did not lyse MBP-pulsed L cells. The ability of the DR2b molecules on transfected cells to stimulate T cells was confirmed with DR2b-allospecific T cell clones. Although five MBP-specific lines were restricted by DR2a, they recognized different parts of the MBP molecule, as demonstrated by the presentation of shorter peptides. Thus, our results suggest that DR2a is a dominant restriction molecule in MBP-specific responses by DR2+ MS patients. The results also indicate that the reported heterogeneity in MBP epitopes recognized by DR2-restricted T cells, may not be due to the use of different restriction elements but rather to the binding of different MBP peptides to DR2a molecules. .A Jaraquemada D; Martin R; Rosen-Bronson S; Flerlage M; McFarland HF; Long EO. .I 275722 .U 91010777 .S J Immunol 9101; 145(9):2896-901 .M Adult; B-Lymphocytes/IM; Blotting, Western; Human; HIV Antibodies/*IM; HIV Antigens/IM; HIV Infections/IM/*MI; HIV Seropositivity/IM; HIV-1/*GD/IM; In Vitro; Leukocytes, Mononuclear/*MI; Middle Age; Neutralization Tests; Reverse Transcriptase/ME; Support, Non-U.S. Gov't. .T Resistance to infection by HIV-1 of peripheral blood mononuclear cells from HIV-1-infected patients is probably mediated by neutralizing antibodies. .P JOURNAL ARTICLE. .W We have investigated whether PBMC of HIV-1-seropositive subjects are as susceptible to in vitro infection by HIV-1 as are PBMC from seronegative controls. Accordingly, stimulated PBMC from 19 HIV-1-infected subjects were inoculated with four different variants of HIV-1. None of these cultures produced either detectable quantities of viral reverse transcriptase activity or p24 Ag following inoculation with HIV-1. In contrast, in five of six cases in which these PBMC were depleted of B cells by antibody plus complement prior to viral inoculation, the presence of viral reverse transcriptase and p24 Ag was detected. The presence of normal levels of CD4-Ag at the surface of the CD4+ cells in these populations was established by flow cytometry. Analysis by an immunoblot assay revealed that anti-HIV antibodies were present in the sera obtained from these infected donors; in addition, 7 of 10 culture fluids derived from the nondepleted PBMC were shown to contain virus-neutralizing antibodies. Cultures which were depleted of B cells did not contain detectable levels of antiviral antibodies. Confirmation that the virus produced by the PBMC which had been depleted of B cells was of the strain used to infect the cultures, rather than that which initially caused patient infection, was provided on the basis of differential susceptibility to antibody neutralization. These results suggest that antibodies produced by B cells in cultures of PBMC from seropositive donors may restrict infection by HIV-1 of such cultures under laboratory conditions. .A Tremblay M; Numazaki K; Li XG; Gornitsky M; Hiscott J; Wainberg MA. .I 275723 .U 91010779 .S J Immunol 9101; 145(9):2908-13 .M Camptothecin/PD; Cell Line; Cell Survival/*DE; Coumarins/PD; Drug Synergism; DNA Gyrase/*AI; DNA Untwisting Proteins/*AI; In Vitro; L Cells; Novobiocin/PD; Support, U.S. Gov't, P.H.S.; Teniposide/PD; Tumor Necrosis Factor/*TO. .T Synergistic interactions between tumor necrosis factor and inhibitors of DNA topoisomerase I and II. .P JOURNAL ARTICLE. .W TNF is a pleiotropic cytokine that mediates diverse cellular responses, including cytotoxicity, cytostasis, proliferation, differentiation, and the expression of specific genes. Many of these processes require the activity of DNA topoisomerases I and II. We have investigated the interactions of TNF with inhibitors of both topoisomerases in 16-h assays using the murine L929 and human ME-180 cell lines, which undergo a cytotoxic TNF response. Camptothecin, a specific inhibitor of topoisomerase I, enhanced TNF cytotoxicity 150-fold against both cell lines. The topoisomerase II inhibitors VM-26 and VP-16, which stabilize covalent DNA-topoisomerase intermediates, greatly enhance TNF cytotoxicity against both cell lines. The most effective, VM-26, can lower the TNF LD50 to femtomolar levels. In contrast, the topoisomerase II inhibitors novobiocin and coumermycin, which bind to the enzyme ATPase site, protect L929 cells from TNF cytotoxicity but enhance TNF cytotoxicity in ME-180 cells. The large changes in TNF sensitivity induced by drug concentrations that by themselves show no effect, and the opposing synergistic effects of inhibitors with different inhibitory mechanisms (in L929 cells), suggest the active involvement of topoisomerases in TNF-mediated cytotoxicity. The correlation of cytotoxic synergy with the stabilization of DNA strand breaks indicates that DNA damage may play a significant role in TNF-mediated cytotoxicity. .A Baloch Z; Cohen S; Coffman FD. .I 275724 .U 91010782 .S J Immunol 9101; 145(9):2925-31 .M Animal; Anisomycin/PD; Arsenic/PD; Cell Survival/*DE; Cells, Cultured; Cytochalasins/PD; Heat/*; Heat-Shock Proteins/*PH; In Vitro; Mice; Receptors, Endogenous Substances/ME; Support, U.S. Gov't, P.H.S.; Tumor Necrosis Factor/ME/*TO. .T Induction of the heat shock response protects cells from lysis by tumor necrosis factor. .P JOURNAL ARTICLE. .W A minority of transformed cell lines are directly susceptible to lysis by TNF, whereas many cells can be made sensitive to TNF by treatment with inhibitors of protein synthesis. Other groups have shown that exposure to TNF induces in many cells a transcription/translation dependent response that protects the cell from TNF lysis. Heat shock proteins are involved in protecting cells from the lethal affects of heat and other metabolic poisons. In this report, we test the possibility that heat shock proteins are also involved in protecting cells from lysis by TNF. We find that after induction of the cellular heat shock response by either heat or arsenite treatment, both spontaneously TNF-sensitive cells and those cells made sensitive by inhibition of protein synthesis are nearly completely protected from TNF cytolysis. The heat-treated cells retained most of their capacity to bind TNF, suggesting that heat shock functions at a postreceptor binding phase of the lytic process. Mouse C3HA fibroblasts are also made sensitive to TNF lysis by treatment with cytochalasin E. We have previously found that elicitation of the cell's TNF-protective response by exposure to TNF suppresses killing of C3HA by subsequent treatment with TNF plus cytochalasin E. In contrast, we report here that induction of the heat shock response did not provide significant protection to C3HA from killing by TNF in the presence of cytochalasin E. Thus, although induction of heat shock proteins does protect cells from TNF, they appear to act by a mechanism distinct from that elicited by TNF itself. .A Kusher DI; Ware CF; Gooding LR. .I 275725 .U 91010783 .S J Immunol 9101; 145(9):2932-7 .M Blotting, Northern; Cells, Cultured; Gene Expression; Human; In Vitro; Inflammation/PP; Interleukin-1/*GE/PD; Neutrophils/*PH; RNA, Messenger/GE; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tumor Necrosis Factor/PD. .T Cytokine regulation of IL-1 beta gene expression in the human polymorphonuclear leukocyte. .P JOURNAL ARTICLE. .W Although recently polymorphonuclear leukocytes (PMN) have been identified as producers of IL-1 beta in response to LPS and granulocyte/monocyte colony stimulating factor, little is known regarding the ability of other cytokines to induce the production of IL-1 beta in the PMN. Inasmuch as IL-1 and TNF have been shown to be important priming agents, as well as agents that induce migration of PMN, we investigated their effect on IL-1 beta gene expression in human peripheral blood PMN. In the present study, we demonstrate that human peripheral blood PMN produce IL-1 beta in response to IL-1 alpha, IL-1 beta, and TNF-alpha. Control (unstimulated) human PMN had virtually undetectable levels of IL-1 beta mRNA. Either IL-1 beta or TNF, induced PMN to transiently express IL-1 beta mRNA with peak expression at 1 h, returning to untreated levels by 2 h. A dose response indicated that as little as 0.05 ng/ml of IL-1 beta or TNF resulted in IL-1 beta induction, with maximal effects at 1 ng/ml of IL-1 beta and 5 ng/ml of TNF. IL-1 alpha or IL-1 beta exhibited similar dose responses in IL-1 beta mRNA induction. Inasmuch as cytokines have been shown to have synergistic effects in cell function studies, we induced PMN with a combination of maximally effective doses of TNF plus IL-1 beta. They demonstrated a cooperative effect on IL-1 beta gene expression, in that mRNA levels were sustained for three hours. IL-1 beta Ag expression, as measured by ELISA, paralleled IL-1 beta mRNA expression with cell associated peak levels at 2 to 4 h. IL-1 beta Ag levels in PMN lysates and supernatants correlated with IL-1 beta mRNA levels, i.e., TNF + IL-1 greater than TNF greater than IL-1. Thus, these studies represent the first demonstration of IL-1 and TNF induction of IL-1 beta gene expression in the PMN. Furthermore, the time course of induction is unique to the PMN, with peak induction of mRNA at 1 h, which is consistent with the short lived nature of these cells in inflammatory lesions. .A Marucha PT; Zeff RA; Kreutzer DL. .I 275726 .U 91010785 .S J Immunol 9101; 145(9):2946-9 .M Blotting, Northern; Cell Membrane/ME; Cells, Cultured; Human; In Vitro; Lymphocytes/*ME; Macromolecular Systems; Receptors, Interleukin-2/GE/*ME; RNA, Messenger/GE; Support, Non-U.S. Gov't; Time Factors. .T Expression of the human IL-2 receptor on lymphocytes involves rapid turnover of its p55 alpha-subunit (Tac). .P JOURNAL ARTICLE. .W Upon mitogenic stimulation, both mRNA encoding the p55 alpha-subunit (Tac) of the human IL-2R alpha and IL-2R alpha protein are induced and expressed in tonsil lymphocyte populations over several days. Using a quantitative dot-blot immunoassay for the IL-2R alpha subunit, a rapid disappearance of this polypeptide from cells is demonstrated in the presence of the translation inhibitor, cycloheximide. The half-life of IL-2R alpha subunit protein is 2 to 3 h. This decline in cell-associated IL-2R alpha subunit is matched by a rapid decline in IL-2R alpha on the cell surface and is not accompanied by any increase in soluble IL-2R alpha protein. Long term expression of the IL-2R on the cell surface is thus the result of continual synthesis and rapid breakdown of IL-2R alpha chains in the cell. Steady state expression of the IL-2R after an immune stimulus hence depends upon continuous expression of the IL-2R alpha subunit gene. Rapid turnover of the unstable alpha-subunit on the cell surface provides a novel mechanism for sensitive control of functional IL-2R expression. .A Sayar D; Ketzinel M; Gerez L; Silberberg C; Reshef A; Kaempfer R. .I 275727 .U 91010786 .S J Immunol 9101; 145(9):2950-8 .M Antibody-Dependent Cell Cytotoxicity; Antigens, Differentiation/ME/PH; Cell Survival/DE; Cytokines/*PD; Cytotoxicity, Immunologic/*/DE; Dose-Response Relationship, Drug; Eosinophils/*DE; Human; Interferon Alfa, Recombinant/PD; Interferon Type I/PD; Interferons/*PD; Neutrophils/DE; Receptors, Fc/ME/PH; Time Factors. .T Effects of IFN on human eosinophils in comparison with other cytokines. A novel class of eosinophil activators with delayed onset of action. .P JOURNAL ARTICLE. .W Extracellular killing is regarded as one of the main functions of eosinophils. Therefore, a cytotoxicity assay against antibody-coated Daudi-lymphoma cells was established to measure cytokine effects on peripheral blood eosinophils from healthy volunteers. Optimal time of exposure to cytokines and half optimal concentrations (EC50) were determined and the capability of various cytokines to enhance cytotoxicity of eosinophils was compared. Thus, after 24 h with cytokine, the highest activation of eosinophils was observed with recombinant human rhIFN-gamma (EC50 = 0.2 U/ml), followed by the known activators of eosinophils recombinant human granulocyte/macrophage CSF (rhGM-CSF), rhIL-3, and murine IL-5 (mIL-5). rhIFN-alpha and natural human IFN-beta (nhIFN-beta) enhanced cytotoxicity as well. On the other hand, in short term assays, eosinophils were not stimulated by IFN and the strongest stimulator was rhGM-CSF (EC50 = 0.2 U/ml), followed by rhIL-3, mIL-5, rhTNF, and rhIL-4. With rhTNF-alpha enhancement was more pronounced on freshly isolated eosinophils (EC50 = 0.6 U/ml) and declined with time. No significant stimulation was detected with rhG-CSF, rhIL-1 beta, rhIL-2, rhIL-6, and rhIL-8. On neutrophils, rhIL-8 enhanced cytotoxicity, but the stimulation was weak in relation to other neutrophil activators. Studies on the mechanism of cytotoxic activity revealed that cytotoxicity required opsonization of targets with specific antibody. FMF analysis was performed demonstrating that freshly isolated eosinophils express Fc-gamma RII (CD32), small amounts of Fc-gamma RIII (CD16), but not Fc-gamma RI (CD64). In experiments with blocking antibodies to Fc-gamma R cytotoxicity was restricted to Fc-gamma RII. Expression of Fc-gamma RII was not enhanced by rhGM-CSF, rhTNF-alpha, and mIL-5, but a significant increase in the number of positive cells was observed after incubation with rhIFN-gamma for 24 h (p less than 0.05). In addition, enhanced viability of eosinophils was observed when cultured in the presence of rhIFN-gamma, rhIFN-alpha, rhGM-CSF, and rhTNF-alpha, but not of rhG-CSF and rhIL-2. Thus, IFN appear to be another class of activators of eosinophils, characterized by their delayed type of action. .A Valerius T; Repp R; Kalden JR; Platzer E. .I 275728 .U 91010787 .S J Immunol 9101; 145(9):2959-66 .M Animal; Antibodies, Monoclonal/IM; Antigens, Differentiation/CH/GE/*IM; Antigens, Surface/AN; Base Sequence; Exons; Flow Cytometry; Histocompatibility Antigens/CH/GE/*IM; Intestinal Mucosa/CY/*IM; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Molecular Weight; Peptide Mapping; Polymerase Chain Reaction; Precipitin Tests; Protein Processing, Post-Translational; T-Lymphocyte Subsets/*IM. .T Characterization of the CD45 molecule on murine intestinal intraepithelial lymphocytes. .P JOURNAL ARTICLE. .W The CD45 molecule was analyzed from murine intestinal intraepithelial lymphocytes (IEL). Immunofluorescent staining of CD8+ IEL revealed varying degrees of reactivity with mAb specific for CD45-restricted determinants, some which are typically expressed only by B cells. Immunoprecipitation of CD45 molecules from IEL yielded an array of proteins with apparent (m.w.) ranging from 180,000 to 260,000. The m.w. 260,000 form was restricted to IEL, was distinct from the B220 molecule, and was the only CD45 isoform that expressed the CD45-associated carbohydrate differentiation Ag CT1. Moreover, the CT1 determinant was present on cells of the Thy-1- but not the Thy-1+ IEL subset. Sequential immunoprecipitation studies indicated that expression of the m.w. 260,000 protein was not restricted to CT1+ cells. The protein composition of the m.w. 260,000 CD45 isoform was examined by using the polymerase chain reaction for analysis of CD45 variable exon usage. In contrast to B cells in which the major CD45 mRNA contained all three variable exons (exons 4, 5, and 6), IEL CD45 mRNA contained significant amounts of two-exon, single exon, and zero variable exon forms. Restriction enzyme analysis identified the single exon form as exon 5 and the two-exon form as a mixture of exons 4 and 5 and exons 5 and 6. Metabolic labeling of CD45 in pulse-chase experiments suggested that the generation of this high m.w. protein was caused by post-translational modifications, perhaps glycosylation. Overall, the results indicated that the high m.w. form of CD45 and the addition of the CT1 determinant were generated via IEL-specific post-translational modifications and not by novel alternate exon usage. .A Goodman TG; Chang HL; Esselman WJ; LeCorre R; Lefrancois L. .I 275729 .U 91010788 .S J Immunol 9101; 145(9):2967-73 .M Animal; B-Lymphocytes/*ME/UL; Calcium/PH; Calcium-Binding Proteins/*ME; Cell Compartmentation; Cell Line; Cell Membrane/ME; Cytoplasm/ME; Cytoskeleton/*ME; Fluorescent Antibody Technique; IgM/*ME; Immunologic Capping/*; Mice; Molecular Weight; Osmolar Concentration; Signal Transduction; Solubility; Support, Non-U.S. Gov't. .T The lymphocyte-specific protein LSP1 is associated with the cytoskeleton and co-caps with membrane IgM. .P JOURNAL ARTICLE. .W LSP1 is a lymphocyte-specific intracellular Ca2(+)-binding protein. We found previously that a fraction of the total cellular pool of LSP1 protein accumulates at or near the cytoplasmic face of the plasma membrane. LSP1 protein was also shown to be present in the cytoplasm. Here we report that approximately 10% of the total intracellular LSP1 protein is associated with the Nonidet P-40 insoluble cytoskeleton of the mIgM+, mIgD+ B lymphoma cell line BAL17. Variation in conditions of extraction did not alter this value. To rule out the possibility that LSP1 associates with the nucleus that is also present in the detergent insoluble pellet, we prepared a separate nuclear fraction essentially free of cytoskeletal material and found only trace amounts of LSP1 protein. After accounting for yield losses during subcellular fractionation by measuring the recovery of 125I-labeled membrane IgM, or of the cytoplasmic marker enzyme lactate dehydrogenase activity, the LSP1 in membrane fractions was calculated to represent approximately 30% of the total cellular LSP1 and cytoplasmic LSP1 accounted for approximately 55% of the total. Approximately 75% of the plasma membrane LSP1 protein was soluble in 1% Nonidet P-40 containing buffer, indicating that the majority of the LSP1 in the plasma membrane fraction was distinct from the cytoskeletal LSP1 protein. The preparation of membrane fractions in the presence of 1 M NaCl, or washing of membranes in 3 M KCl did not diminish the levels of membrane LSP1. These results show the existence of three discrete intracellular LSP1 pools. Double label immunofluorescence studies showed that the peripheral ring-like distribution of LSP1 in BAL17 cells became a distinct cap upon cross-linking the mIgM. These intracellular LSP1 caps were always found to be located directly underneath the mIgM caps. .A Klein DP; Galea S; Jongstra J. .I 275730 .U 91010789 .S J Immunol 9101; 145(9):2974-83 .M Amino Acid Sequence; Animal; Antigens, Differentiation, B-Lymphocyte/CH/GE/IM; Base Sequence; Blotting, Northern; Cloning, Molecular; Comparative Study; DNA/GE; Genes, Structural; Mice; Molecular Sequence Data; Peptide Mapping; Precipitin Tests; Receptors, Complement/CH/*GE/IM; Recombinant Fusion Proteins/GE/IM/IP; Restriction Mapping; Support, Non-U.S. Gov't. .T A molecular and immunochemical characterization of mouse CR2. Evidence for a single gene model of mouse complement receptors 1 and 2. .P JOURNAL ARTICLE. .W The relationships between functional, biochemical, and genetic homologues of human and mouse C receptors 1 (CR1) and 2 (CR2) are incompletely understood. We have isolated and characterized a partial mouse CR2 cDNA clone and determined the exon-intron organization of the gene encoding it. Together they predict a form of mouse CR2 highly identical to the 15 short consensus repeat form of human CR2. Strong similarities in genomic organization and exon-intron junctions indicate that this mouse gene and human CR2 are evolutionary homologues. A polyclonal rabbit anti-mouse CR2 fusion protein, BRN-1, was prepared. BRN-1 immunoprecipitates bands of 155 to 160 kDa under nonreducing conditions in mouse CR2 expressing B cell lines. In mouse spleen a doublet of 155 kDa and 190 kDa under nonreducing and 165 and 205 kDa under reducing conditions is recognized by immunoprecipitation and Western blot analysis. Staphylococcus aureus V8 protease maps of these two proteins show many shared bands. Crossed immunoprecipitation using BRN-1 and 7E9, a previously described mAb reported to identify the 190-kDa mouse CR1 and a smaller 150-kDa protein, indicates that both antibodies react with the same proteins. Therefore, by using BRN-1 we have now linked the genetic mouse CR2 to its functional, biochemically characterized gene product. The observation that BRN-1 also recognizes a second 190-kDa mouse protein defined functionally as a homologue of human CR1, and that these proteins have very similar peptide maps, provides strong evidence that these two proteins are expressed by a single mouse CR2/CR1 transcription unit. .A Molina H; Kinoshita T; Inoue K; Carel JC; Holers VM. .I 275731 .U 91010790 .S J Immunol 9101; 145(9):2984-8 .M Antibodies, Monoclonal; Blood Platelets/*ME; Collagen/*ME; Complement 1q/*ME; Human; In Vitro; Molecular Weight; Platelet Adhesiveness; Platelet Membrane Glycoproteins/ME; Receptors, Complement/*ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Platelet C1q receptor interactions with collagen- and C1q-coated surfaces. .P JOURNAL ARTICLE. .W We recently described specific binding sites for C1q on human blood platelets. Structural similarities between the amino-terminal of C1q and collagen have suggested that receptors for both molecules on platelets might be the same. The present study thus compared the interaction of purified C1q receptors (C1qR) and whole platelets with collagen- and C1q-coated polystyrene surfaces. Surfaces coated with BSA or gelatin served as controls. Purified 125I-labeled C1qR recognized both C1q- and collagen-coated surfaces in a divalent, cation-independent manner. This adhesion was inhibited by polyclonal or monoclonal (II1/D1) anti-C1qR antibodies. Although C1qR adhered preferentially to C1q-coated surfaces, adhesion to bovine and human type I collagen, as well as to human type III and V collagen, was also noted. In parallel studies, 51Cr-labeled platelets bound equally well to collagen- or C1q-coated surfaces, albeit in a magnesium-dependent manner. Partial inhibition of platelet adhesion was observed in the presence of RGDS, despite the inability of RGDS to modify C1qR interaction with C1q or collagen. Moreover, anti C1qR antibodies selectively inhibited platelet adhesion to C1q-coated surfaces, whereas antibodies specific for the GPIa/IIa collagen receptor (6F1) preferentially inhibited platelet collagen interactions. These data support the presence of distinct platelet membrane C1qR, which may cross-react with collagen, and suggest that C1qR are necessary but not sufficient for platelet adhesion to C1q-coated surfaces. Additional divalent cation and/or RGD-sensitive binding sites may participate. .A Peerschke EI; Ghebrehiwet B. .I 275732 .U 91010792 .S J Immunol 9101; 145(9):2994-3001 .M Animal; Antibodies, Anti-Idiotypic/*IM; Antibodies, Monoclonal/*IM; Antibody Specificity; Bacterial Vaccines/IM; Binding Sites, Antibody; Chickens; Cross Reactions; Immunization, Passive; Immunoglobulin Idiotypes/*IM; Lipid A/*IM; Lipopolysaccharides/*IM; Mice; Mice, Inbred Strains; Rabbits; Salmonella typhimurium/IM; Salmonella Infections, Animal/PC; Shock, Septic/*PC; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Analysis of the immune response to lipopolysaccharide. Existence of an interspecies cross-reactive idiotype associated with anti-lipid A antibodies. .P JOURNAL ARTICLE. .W LPS is the major surface glycolipid on gram-negative bacteria. In this work, we have idiotypically characterized the antibody response against LPS in different species. To do this, we have produced mAb against LPS. Binding of many of these antibodies to LPS could be inhibited by LPS and lipid A, indicating that the monoclonals are specific for lipid A, the toxic moiety of the LPS molecule. One anti-lipid A antibody, IC9, proved protective against gram-negative bacteremia and endotoxic shock in murine protection models. We generated anti-idiotypic antibodies against IC9. The binding of several of these anti-Id to IC9 was specifically inhibited by lipid A. We used these anti-Id to characterize the anti-LPS response, and the results revealed that the IC9 Id is conserved in different species. The importance of an interspecies cross-reactive Id in the response to endotoxin and its relevance in vaccine development for septic shock are discussed. .A Su SD; Ward MM; Apicella MA; Ward RE. .I 275733 .U 91010795 .S J Immunol 9101; 145(9):3017-25 .M Alkaline Phosphatase/ME; Human; In Vitro; Lipopolysaccharides/ME/*PD; Monocytes/PH; N-Formylmethionine Leucyl-Phenylalanine/PD; Neutrophils/DE/*PH; Plasma/*PH; Polymyxin B/PD; Superoxide/*ME; Support, U.S. Gov't, P.H.S.; Time Factors; Tumor Necrosis Factor/*PD. .T Priming of neutrophils by lipopolysaccharide for enhanced release of superoxide. Requirement for plasma but not for tumor necrosis factor-alpha. .P JOURNAL ARTICLE. .W When human neutrophils are incubated with LPS, they become primed for enhanced release of O2- in response to stimulation by FMLP. We investigated two aspects of LPS priming: 1) whether priming depends on secretion of TNF-alpha by monocytes present in neutrophil preparations, and 2) whether plasma is required for priming. Using plasma-Percoll gradients, we isolated neutrophils that contained only 0.1% monocytes. At 37 degrees C, these neutrophils were significantly primed by LPS (100 ng/ml) within 30 min. In contrast, LPS-treated monocytes required 60 min to secrete significant neutrophil-priming activity, the major component of which was TNF-alpha. Further, antibody against TNF-alpha failed to inhibit priming of neutrophils by LPS at 15, 30, and 45 min, and inhibited only 15% at 60 min. The results suggested that TNF-alpha or other factors from monocytes were not essential for priming of neutrophils by LPS. Neutrophils that had been washed free of plasma by centrifugation through 50% Percoll responded only weakly to LPS with respect to priming for enhanced O2- release and increased expression of alkaline phosphatase activity on the cell surface. Priming of washed neutrophils could be restored by adding back plasma (0.1 to 1.0%). This effect of plasma was not blocked by heating the plasma to 56 degrees C but was blocked at 100 degrees C. LPS priming could be blocked by polymyxin B, even in the presence of plasma. Thus, priming required both LPS and plasma. Neutrophils incubated with LPS in the absence of plasma were not primed by subsequent addition of plasma, but were primed by addition of plasma and LPS. Culture supernatants from neutrophils incubated with 20 ng/ml LPS in the absence of plasma failed to prime fresh neutrophils, but supernatants from neutrophils incubated with LPS in the presence of 1% plasma were able to prime fresh neutrophils. These results implied that neutrophils inactivated LPS and that plasma protected LPS from inactivation. Nevertheless, such inactivated LPS retained the ability to gel Limulus lysate at 10 pg/ml, and the ability to prime monocytes at 100 pg/ml. Thus, plasma prevented a neutrophil-specific inactivation of LPS. .A Aida Y; Pabst MJ. .I 275734 .U 91010796 .S J Immunol 9101; 145(9):3026-32 .M Alprostadil/PD; Antigen-Antibody Complex/CH/*PH; Antigens, Differentiation/CL/*PH; Cytochalasin B/PD; Enzyme Activation; Human; In Vitro; N-Formylmethionine Leucyl-Phenylalanine/PD; NADH, NADPH Oxidoreductases/*ME; Pertussis Toxins/PD; Receptor Aggregation; Receptors, Fc/CL/*PH; Signal Transduction; Solubility; Superoxide/ME; Support, U.S. Gov't, P.H.S.; Time Factors. .T Soluble and insoluble immune complexes activate human neutrophil NADPH oxidase by distinct Fc gamma receptor-specific mechanisms. .P JOURNAL ARTICLE. .W Signal transduction initiated by interaction of immune complexes (IC) with Fc gamma RII and Fc gamma RIII receptors on human neutrophils was studied by investigating the capacity of well-defined complexes to stimulate O2- generation in neutrophils. IC consisting of polyclonal rabbit antibody to human albumin were prepared at equivalence (insoluble complexes) and at five times Ag excess (soluble complexes). Stimulation of human neutrophils with soluble and insoluble IC caused a dose-dependent activation of the respiratory burst and O2- generation. Incubation of neutrophils with cytochalasin B significantly enhanced O2- generation in neutrophils stimulated with soluble IC. In contrast, cytochalasin B treatment had a minimal effect on O2- generation in neutrophils stimulated with insoluble IC. Treatment of neutrophils with PGE1 or pertussis toxin (PTx) significantly inhibited O2- generation by soluble IC-stimulated neutrophils. However, neither PGE1 nor PTx treatment significantly altered O2- generation in neutrophils stimulated with insoluble complexes. Although O2- generation induced by soluble IC was significantly inhibited by mAb against both Fc gamma RII and Fc gamma RIII receptor, insoluble IC stimulation of neutrophil O2- generation was significantly diminished only by mAb against Fc gamma RIII receptor. Cross-linking of either Fc gamma RII or Fc gamma RIII receptors on neutrophil surfaces induced O2- generation, and this activation was inhibited by both PGE1 and PTx treatment. These findings indicate that soluble and insoluble ICs induce O2- production in human neutrophils through distinct mechanisms. Soluble IC induce activation of neutrophils through a PTx- and PGE1-sensitive pathway that is dependent upon both Fc gamma RII and Fc gamma RIII receptors. Although insoluble IC induce O2- production through a PTx and PGE1 insensitive pathway mediated primarily through Fc gamma RIII receptor. .A Crockett-Torabi E; Fantone JC. .I 275735 .U 91010797 .S J Immunol 9101; 145(9):3033-40 .M Cell Adhesion; Cell Degranulation/DE; Cytochalasin B/PD; Endothelium, Vascular/CY/*ME; Human; In Vitro; Interleukin-1/PD; Interleukin-8/CH/GE/IP/*ME; Leukocytes/*PH; N-Formylmethionine Leucyl-Phenylalanine/PD; Neutrophils/CY/*PH; Pancreatopeptidase/ME; Receptors, Immunologic/PH; Recombinant Proteins; Structure-Activity Relationship; Thrombin/ME; Transfection. .T Endothelial and leukocyte forms of IL-8. Conversion by thrombin and interactions with neutrophils. .P JOURNAL ARTICLE. .W We have recently shown that endothelial cell-derived IL-8 inhibits neutrophil adhesion to IL1-beta-activated human umbilical vein endothelial cell monolayers. IL-8 secreted by T lymphocytes or monocytes has been characterized as a promoter of neutrophil degranulation and chemotaxis. The IL-8 isolated from each of these cell types is a mixture of two IL-8 polypeptides, one consisting of 72 amino acids (herein called [ser-IL-8]72) and the other 77 amino acids (an N-terminal extended form herein called [ala-IL-8]77). IL-8 derived from T lymphocytes and monocytes is predominantly [ser-IL-8]72, whereas endothelial-derived IL-8 is highly enriched (greater than 80%) in [ala-IL-8]77. We address the relationship and activities of these two forms of IL-8 using recombinant proteins expressed by both mammalian cells and Escherichia coli. Thrombin was found to efficiently convert [ala-IL-8]77 to [ser-IL-8]72. In contrast, urokinase and tissue-type plasminogen activator were unable to cleave [ala-IL-8]77, and trypsin generated multiple IL-8 cleavage fragments. In competitive binding assays using 125I[ala-IL-8]77 neutrophils exhibited a twofold preference for [ser-IL-8]72 over [ala-IL-8]77. Both forms of IL-8 inhibited neutrophil adhesion to IL-1-beta-activated HUVEC monolayers by up to 90%. However, [ser-IL-8]72 was approximately 10-fold more potent than [ala-IL-8]77 in these assays (ED50 approximately 0.3 nM for [ser-IL-8]72 vs approximately 3 nM for [ala-IL-8]77. Both forms of IL-8 promoted degranulation of cytochalasin B-treated neutrophils [[ser-IL-8]72 (ED50 greater than 10 nM) was two- to three-fold more potent than [ala-IL-8]77], although in this regard they were less active than FMLP. Our data suggest that [ala-IL-8]77 and [ser-IL-8]72 have qualitatively similar and potentially complex biological activities, and that full activation of IL-8 requires cleavage to the [ser-IL-8]72 form. In the case of inflamed endothelial cells this activation could be mediated by thrombin generated in the procoagulant environment associated with these cells. .A Hebert CA; Luscinskas FW; Kiely JM; Luis EA; Darbonne WC; Bennett GL; Liu CC; Obin MS; Gimbrone MA Jr; Baker JB. .I 275736 .U 91010798 .S J Immunol 9101; 145(9):3041-6 .M Animal; Bone Marrow/CY; Concanavalin A/PD; Cyclosporins/PD; Cytokines/AI/PH; Dexamethasone/*PD; Histamine Liberation/*DE; Histidine Decarboxylase/ME; Hydrocortisone/PD; Hypersensitivity/*PP; Inflammation/PP; Mast Cells/*PH; Rats; Support, Non-U.S. Gov't; Time Factors. .T Inhibition by dexamethasone of histamine production in allergic inflammation in rats. .P JOURNAL ARTICLE. .W In an allergic inflammation model of air pouch type in rats, histamine level in the pouch fluid and histidine decarboxylase activity of pouch wall tissues in the postanaphylaxis phase were increased. Although treatment with dexamethasone failed to inhibit histamine release from mast cells in the anaphylaxis phase, histamine production in the postanaphylaxis phase was inhibited dose dependently. Histamine production-increasing activity in the pouch fluid collected 8 h after the Ag challenge, which was estimated by an activity to stimulate histamine production by bone marrow cells, was decreased by the administration of dexamethasone at the time of the Ag challenge. The addition of steroidal antiinflammatory drugs, dexamethasone, prednisolone, or hydrocortisone, into the incubation medium inhibited the pouch fluid-induced histamine production by bone marrow cells. Hydrocortisone mesylate antagonized the inhibitory effect of dexamethasone on histamine production by bone marrow cells. However, hydrocortisone mesylate failed to recover the decrease in histamine production-increasing activity of the pouch fluid collected from dexamethasone-treated rats. In addition, the dialyzed sample of pouch fluid obtained from dexamethasone-treated nonsensitized rats did not reduce the stimulated histamine production by the pouch fluid sample obtained from the sensitized rats. However, increase in histamine production of bone marrow cells stimulated by the pouch fluid was not inhibited by cyclosporin A that inhibited histamine production induced by Con A. This observation indicates that the pouch fluid has no effect to induce production of the histamine production-increasing factor by bone marrow cells. Consequently, it is suggested that dexamethasone inhibits not only the production of histamine production-increasing factor but also the response of histamine-producing cells to this factor. .A Hirasawa N; Funaba Y; Hirano Y; Kawarasaki K; Omata M; Watanabe M; Mue S; Tsurufuji S; Ohuchi K. .I 275737 .U 91010801 .S J Immunol 9101; 145(9):3062-70 .M Calcimycin/PD; Cell Compartmentation; Cell Fractionation/MT; Cell Membrane/ME; Human; In Vitro; Intracellular Membranes/ME/UL; Microscopy, Electron; Neutrophils/*ME; Phagocytosis; Phagosomes/ME/UL; Platelet Activating Factor/*ME; Subcellular Fractions/CH; Support, U.S. Gov't, P.H.S.. .T The subcellular distribution of platelet-activating factor in stimulated human neutrophils. .P JOURNAL ARTICLE. .W Exposure of human peripheral blood neutrophils to a variety of phagocytic and soluble stimuli is known to induce the synthesis and secretion of platelet-activating factor (PAF), a unique ether-linked phospholipid. It has recently been observed in this laboratory, that whereas some PAF is secreted to the exterior of the cell, the majority of the newly synthesized PAF is retained intracellularly. This observation led us to investigate the subcellular distribution of intracellular PAF in stimulated human neutrophils, and to question the possible intracellular role of this molecule. Approximately 2 x 10(8) neutrophils were exposed to either the phagocytic stimulus, opsonized zymosan particles (25 particles/cell), the soluble stimulus, Ca2(+)-ionophore A23187 (5 micrograms/ml), or were left unstimulated for up to 30 min. After disruption, the cells were fractionated into nuclei, phagolysosomes, specific granules, azurophil granules, membranes, and cytosol. Fractions were analyzed for representative organellar markers, as well as for total protein, total phospholipid phosphorous, and PAF. In cells that had been exposed to opsonized zymosan particles, the majority of the PAF was localized to the phagolysosomal fraction, with lesser amounts being detected in the membranous and granular fractions of the cells. In neutrophils that had been exposed to A23187, the major portion of the PAF was detected in the membranous fractions with smaller amounts being seen in fractions corresponding to the specific granules. On the basis of these data, combined with the known physicochemical properties of PAF, it is speculated that the PAF detected at discrete intracellular locations in stimulated human neutrophils may play an important role in the endocytic and/or secretory functions of neutrophils. .A Riches DW; Young SK; Seccombe JF; Henson JE; Clay KL; Henson PM. .I 275738 .U 91010803 .S J Immunol 9101; 145(9):3080-6 .M Adenoviruses, Human/*IM; Animal; Cell Line; Cell Survival/*DE; Cycloheximide/PD; Cytochalasins/PD; In Vitro; Mice; Microfilaments/DE; Molecular Weight; Oncogene Proteins, Viral/*PD; Support, U.S. Gov't, P.H.S.; Tumor Necrosis Factor/*AI. .T The adenovirus E3-14.7K protein is a general inhibitor of tumor necrosis factor-mediated cytolysis. .P JOURNAL ARTICLE. .W We have previously described a 14,700 m.w. protein (14.7K) encoded by the E3 region of adenovirus that prevents TNF-mediated cytolysis of adenovirus-infected C3HA mouse fibroblasts. In the studies described here we have extended our analysis of TNF cytolysis of C3HA cells and the circumstances under which 14.7K protects these cells from cytolysis. C3HA cells were killed by TNF in the presence of inhibitors of protein synthesis, in the presence of cytochalasin E (which disrupts the microfilaments), and when adenovirus E1A was expressed. As described for other cell types, pretreatment of C3HA cells with TNF prevented cytolysis by TNF plus cycloheximide or TNF plus cytochalasin E, indicating that TNF induces a response that protects against these treatments. Remarkably, when 14.7K was expressed in virus-infected cells, it also prevented TNF-induced lysis whether sensitivity to TNF was induced by inhibition of protein synthesis, disruption of the cytoskeleton by cytochalasin E, or expression of adenovirus E1A. The 14.7K protein also prevented TNF lysis of cells that are spontaneously sensitive to TNF lysis. Thus, 14.7K appears to be a general inhibitor of TNF cytolysis, and as such should be an important tool in unraveling the mechanism of TNF cytolysis. There was one exception; NCTC-929 cells were spontaneously sensitive to TNF lysis and that lysis was not affected by 14.7K even though the protein was made in large quantities and was metabolically stable in these cells. This suggests that there is heterogeneity among TNF-sensitive cell lines. The 14.7K protein was found in both the nuclear and cytosol fractions of TNF resistant as well as all spontaneously sensitive cells suggesting that 14.7K may have more than one site of action within the cell. .A Gooding LR; Sofola IO; Tollefson AE; Duerksen-Hughes P; Wold WS. .I 275739 .U 91010804 .S J Immunol 9101; 145(9):3087-94 .M Amino Acid Sequence; Animal; Antigenic Determinants; Helper Cells/*IM; Hemagglutinins, Viral/*IM; Histocompatibility Antigens Class II/IM; Hybridomas/IM; Lymphocyte Transformation; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Oligopeptides/CS/IM; Orthomyxoviruses Type A/*IM; Structure-Activity Relationship; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T A large degree of functional diversity exists among helper T cells specific for the same antigenic site of influenza hemagglutinin. .P JOURNAL ARTICLE. .W The site-1 determinant of the hemagglutinin molecule of influenza virus (A/PR/8/34) is one of several immunodominant sites in the BALB/c Th cell response to Ha. A synthetic peptide comprising this T cell site (HA110-120), a panel of analogs containing single substitutions in this determinant, and homologs truncated at the amino- or carboxyl-terminal were used to examine the fine specificities of 15 T cells specific for site-1 in the context of I-Ed. The results indicate that every residue within the minimal determinant plays a role in the T cell recognition process, as single substitutions at any of these positions affected the ability of the peptide to stimulate at least some site 1-specific T cells. For the majority of the residues examined, substitutions had dissimilar effects on distinct T cells, indicating that the substituted residues were affecting recognition in a receptor-specific manner. Each of the 15 T cells examined had a distinct fine specificity pattern, suggesting that the BALB/c T cell repertoire for this site is likely to exceed 100 distinct clonotypes. .A Haberman AM; Moller C; McCreedy D; Gerhard WU. .I 275740 .U 91010807 .S J Immunol 9101; 145(9):3105-10 .M Amino Acid Sequence; Antibodies, Monoclonal/IM; Antibodies, Viral/*IM; Antigenic Determinants; B-Lymphocytes/*IM; Molecular Sequence Data; Oligopeptides/CS/IM; Oncogene Proteins, Viral/GE/*IM; Papillomaviruses/*IM; Precipitin Tests; Recombinant Fusion Proteins/GE/IM; Support, Non-U.S. Gov't; Viral Proteins/GE/*IM. .T Identification of B-epitopes in the human papillomavirus 18 E7 open reading frame protein. .P JOURNAL ARTICLE. .W A panel of murine mAb raised against a MS2 replicase/HPV 18 E7 fusion protein included 23 reactive by ELISA with HPV 18 E7 determinants. A total of 19 of the 23 recognized linear epitopes in the N-terminal region of the E7 molecule, while the other four were deduced by binding inhibition assays to recognize conformational determinants in this region. All tested antibodies precipitated a 14-kDa peptide doublet that corresponded with the predicted size of the E7 protein, from HeLa cells, but not from HPV 16 E7 containing CaSki cells. HPV 18 E7 protein was detected by immunolabeling with electron microscopy in both the nucleus and the cytoplasm of HeLa cells with the greater proportion occurring in the cytoplasm. No antibody reacted specifically by indirect immunofluorescence with HeLa cells. Weak cross-reactivity of some mAb with the E6 MS2-replicase fusion protein of HPV 16 was detected by ELISA, but no protein of the appropriate size was immunoprecipitated from CaSki cells. It is concluded that the B cell epitopes on the HPV 18 E7 transforming protein are located in the N-terminal region of the molecule and that some are weakly cross-reactive with HPV 16 E6 protein. E7 protein is either present in HeLa cells at a concentration too low to be detected by indirect immunofluorescence, or the N-terminal epitopes are masked by protein conformation or interaction with cellular or other viral components. .A Selvey LA; Tindle RW; Geysen HM; Haller CJ; Smith JA; Frazer IH. .I 275741 .U 91010808 .S J Immunol 9101; 145(9):3111-8 .M Animal; Blotting, Northern; Cell Line; Cloning, Molecular; DNA Probes; Gene Expression; Lymphocytes/*PH; Lymphoid Tissue/PH; Mice; Mice, Inbred Strains; Ribonucleases; RNA, Messenger/GE; Serine Proteinases/*GE; Support, Non-U.S. Gov't; T-Lymphocyte Subsets/PH; Tissue Distribution. .T Cell specificity of granzyme gene expression. .P JOURNAL ARTICLE. .W Granzymes are serine proteases present in secretory granules of cytolytic T lymphocyte lines. We have studied the expression of the granzyme family (granzyme A, B, C, D, E, F, and G) in different lymphoid cell populations and cell lines as well as in nonlymphoid cells and tissues. Our data show that with few exceptions expression of granzyme genes is restricted to T cells and their thymic precursors. In mature T cells granzymes are expressed only upon activation. The same is true for thymocytes, with the exception of grazyme A that is expressed also in non-stimulated cells. In T cells and thymocytes the distribution of mRNAs coding for different granzymes depends on the subpopulation tested and the activation protocol. Highly cytolytic PEL express granzymes A and B but none of the other granzymes. .A Garcia-Sanz JA; MacDonald HR; Jenne DE; Tschopp J; Nabholz M. .I 275742 .U 91010809 .S J Immunol 9101; 145(9):3119-25 .M Alleles; Amino Acid Sequence; Base Sequence; Evolution; Gene Conversion; Haplotypes; Human; HLA-DQ Antigens/*GE; HLA-DR Antigens/*GE; Molecular Sequence Data; Negroid Race/GE; Polymerase Chain Reaction; Recombination, Genetic; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.. .T Two divergent routes of evolution gave rise to the DRw13 haplotypes. .P JOURNAL ARTICLE. .W The HLA class II genes and haplotypes have evolved over a long period of evolutionary time by mechanisms such as gene conversion, reciprocal recombination and point mutation. The extent of the diversity generated is most clearly evident in an analysis of the HLA class II alleles present within DRw13 haplotypes. This study uses cDNA sequencing to examine the first domains of DRB1, DRB3, DQA1, and DQB1 alleles from several American black individuals expressing seven different DRw13 haplotypes, five with undefined HLA-D specificities (i.e., not Dw18 or Dw19). Two new DRw13 alleles described in this study are the first examples of convergent evolution of DR alleles in which gene conversion has apparently combined segments of DRB1 alleles encoding DRw11 and DRw8 to generate two new DRB1 alleles, DRB1*1303 and DRB1*1304, that encode molecules bearing serologic determinants of a third allele, DRw13. These new DRw13 alleles are found embedded in haplotypes of DRw11 origin distinct from haplotypes encoding previously identified DRw13 alleles, DRB1*1301 and DRB1*1302. These data suggest that two evolutionary pathways may have given rise to two subgroups of alleles encoding molecules that share DRw13 serologic determinants yet which possess different structural and, likely, functional motifs. Reciprocal gene recombination events resulting in different DR, DRw52 and DQ allele combinations also appear to have played a crucial role in augmenting the level of diversity found in DRw13 haplotypes. Recombination has resulted in the association of one of the new DRw13 alleles with a DQw2 allele normally found associated with DR7 and the association of the DRw52c-associated DRw13 allele (DRB1*1302) with three different DQw1 alleles. The seven DRw13 haplotypes that have resulted from the effect of recombination on haplotypes formed by the two pathways of DRw13 allelic diversification have resulted in different repertoires of class II molecules and, most likely, different immune response profiles in individuals with these haplotypes. .A Lee KW; Johnson AH; Hurley CK. .I 275743 .U 91010810 .S J Immunol 9101; 145(9):3126-35 .M Biological Transport; Blotting, Northern; Calcimycin/PD; Calcium/PH; Cell Compartmentation; Enzyme Activation; Gene Expression Regulation, Neoplastic; Glioma/*GE; Human; HLA-D Antigens/*GE; HLA-DP Antigens/GE; HLA-DR Antigens/GE; In Vitro; Inositol 1,4,5-Trisphosphate/ME; Promoter Regions (Genetics); Protein Kinase C/ME; RNA, Messenger/GE; RNA, Neoplasm/GE; Signal Transduction; Support, Non-U.S. Gov't; Tetradecanoylphorbol Acetate/PD; Transcription, Genetic/DE; Tumor Cells, Cultured. .T Regulation of HLA class II molecule expressions by IFN-gamma. The signal transduction mechanism in glioblastoma cell lines. .P JOURNAL ARTICLE. .W We examined the signal transduction mechanism responsible for the IFN-gamma-induced HLA class II molecule expressions on glioblastoma cell lines, T98G and A172. A series of experiments demonstrated that the activation of protein kinase C (PKC) is involved in the DR and DP molecule expressions on T98G cells. In addition to the activation of PKC, calcium influx appeared to be involved in the DR and DP molecule expressions on T98G. Northern blot analyses with actinomycin D or cycloheximide revealed that these second messengers induce the transcription of DRA and B and DPA and B genes without de novo protein synthesis. Furthermore, we examined the region of the DPB gene that is responsible for IFN-gamma-induced gene transcription by gene transfer of a series of 5' and 3' deletion mutants in which the upstream region of the DPB was linked to a reporter gene, chloramphenicol acetyltransferase. By using these deletion mutants, it appeared that the region between -152 and -126 bp contains a critical IFN-gamma-responsive element. Taken together, these results suggest that IFN-gamma activates PKC and stimulates calcium influx, resulting in the induction of transcription of DRA and B and DPA and B genes without de novo protein synthesis. In DPB gene, we speculate that preexiting protein(s) phosphorylated by PKC in the presence of Ca2+ might directly bind or indirectly interact with the region between -152 and -126 bp of the upstream sequence, leading to the induction of the transcription (possibly in concert with other nuclear protein(s) bound to the promoter sequences). .A Nezu N; Ryu K; Koide Y; Yoshida TO. .I 275744 .U 91010811 .S J Immunol 9101; 145(9):3136-43 .M Adenocarcinoma/IM; Adjuvants, Immunologic; Animal; Dose-Response Relationship, Drug; Immunity, Cellular; Immunization, Passive; Immunologic Memory; Immunosuppression; Interleukin-4/*AD; Lymph Nodes/IM/PA; Mice; Microscopy, Electron; Neoplasms, Experimental/PA/*TH; Recombinant Proteins; Sarcoma, Experimental/IM; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Survival Analysis; T-Lymphocytes/*IM. .T Low doses of IL-4 injected perilymphatically in tumor-bearing mice inhibit the growth of poorly and apparently nonimmunogenic tumors and induce a tumor-specific immune memory. .P JOURNAL ARTICLE. .W The ability of rIL-4 to trigger host reactivity against both a chemically induced fibrosarcoma (CE-2) and a spontaneous adenocarcinoma (TS/A) of BALB/c mice was studied. Daily local s.c. administration around tumor draining lymph nodes of 10 injections of progressive amounts (0.00001 to 1000 pg/day) of rIL-4 induced appreciable inhibition of the growth of both tumors after a dose-response survival curve peaking at 0.1 pg/day. Inasmuch as rIL-4 has no direct antitumor activity, as shown by in vitro tests, host immune reactivity plays a fundamental role in this lymphokine activated tumor inhibition (LATI). LATI, in fact, is abolished when recipient mice are sublethally irradiated or treated with cyclosporin A, or when the reactivity of CD4+ lymphocytes is suppressed, whereas it is not affected by anti-asialo GM1 antibody. The morphologic data show that rIL-4 LATI rests on the recruitment of several cell reaction mechanisms, among which those that are nonspecific seem to predominate. rIL-4 LATI also leads to a state of long lasting and specific immune memory: the growth of a second contralateral tumor challenge is significantly impaired after LATI. This immune memory takes place after LATI of both the poorly immunogenic CE-2 fibrosarcoma and the TS/A adenocarcinoma, previously classed as nonimmunogenic on the basis of immunization-protection tests. In the latter case, adoptive transfer experiments show that Thy-1+ lymphocytes and, in particular, the CD4 cell-depleted T lymphocyte subpopulation, are responsible for the immune memory. Finally, the ability of rIL-4 to trigger LATI is greater than that of the most effective doses of rIL-2, rIL-1 beta, and IFN-gamma, whereas its association with rIL-1 beta induces a more effective immune memory. .A Bosco M; Giovarelli M; Forni M; Modesti A; Scarpa S; Masuelli L; Forni G. .I 275745 .U 91010814 .S J Immunol 9101; 145(9):3150 .M Animal; Antigens, Differentiation, Myelomonocytic/*GE; Base Sequence; Mice; Molecular Sequence Data. .T Nucleotide sequence for the murine CD14 cDNA and gene [letter] .P LETTER. .A Matsuura K; Setoguchi M; Nasu N; Yoshida S; Higuchi Y; Akizuki S; Yamamoto S. .I 275746 .U 91010888 .S J Invest Dermatol 9101; 95(4):371-81 .M Antibodies, Viral/AN; Cytomegaloviruses/IM; Female; Herpesvirus hominis/IM; Human; HIV Seropositivity/*; IgG/AN; IgM/AN; Male; Retroviridae/*IP/UL; Sarcoma, Kaposi's/*MI/PA/UL; Skin/MI/PA/UL; Skin Neoplasms/*MI/PA/UL; Support, Non-U.S. Gov't; Varicella-Zoster Virus/IM. .T Endemic Kaposi's sarcoma in human immunodeficiency virus type 1-seronegative persons: demonstration of retrovirus-like particles in cutaneous lesions. .P JOURNAL ARTICLE. .W In 1984, Greek physicians reported on the clustering of cases of Kaposi's sarcoma (KS) on the Peloponnesus peninsula. To gain more insight into its pathogenesis, we studied the seroepidemiologic and clinicopathologic characteristics of 12 Greek KS patients (eight male/four female) five of whom were residents of an endemic area on the Peloponnesus. These patients were in good general health with ages ranging from 48 to 80 years, had no clinical signs of immunodeficiency, and combined the features of both classic and epidemic KS in that they displayed not only involvement of acral areas but also widespread mucocutaneous lesions. Routine laboratory data were within normal limits; no patient had HTLV-1 and HIV-1/2 antibodies, but all patients had antibodies to several herpesviruses. The histopathology was characteristic of KS with the peculiar feature of a dense infiltrate composed predominantly of CD4+ T lymphocytes. Immunoenzymatic/morphologic studies of the KS cells were consistent with their origin from lymphatic endothelium. Outstanding ultrastructural findings were tubuloreticular structures and cylindrical confronting cisternae, structures that are indicative of an ongoing viral infection. Indeed, extensive electronmicroscopic studies resulted in the detection of retrovirus-like particles in close association to KS cells in five of 12 patients. This in situ observation opens the possibility that this retro-virus contributes to KS development. .A Rappersberger K; Tschachler E; Zonzits E; Gillitzer R; Hatzakis A; Kaloterakis A; Mann DL; Popow-Kraupp T; Biggar RJ; Berger R; et al. .I 275747 .U 91010889 .S J Invest Dermatol 9101; 95(4):382-7 .M Animal; Cell Line; Cell Transformation, Neoplastic/*; DNA Insertion Elements; DNA Replication; Fibroblasts/CY; Human; Keratinocytes/*CY; Mice; Mice, Inbred BALB C; Moloney Leukemia Virus/*GE; Proviruses/GE; Restriction Mapping; Transcription, Genetic; Transfection/*; Transforming Growth Factor alpha/BI/*GE/PH. .T Retroviral expression of transforming growth factor-alpha does not transform fibroblasts or keratinocytes. .P JOURNAL ARTICLE. .W Transforming growth factor alpha (TGF alpha) is a peptide so named because it helps to impart anchorage-independent growth to normal rat kidney (NRK) cells in vitro and is secreted by many rodent and human tumor cells. To directly investigate the transforming properties of this factor, we constructed a replication-defective murine retrovirus that expresses the human sequence coding for TGF alpha. Infection of NIH/3T3 cells with the TGF alpha retrovirus led to the integration of a transcriptionally active provirus and overexpression of biologically active TGF alpha, but failed to induce morphologic transformation. Similarly, the TGF alpha retrovirus failed to induce morphologic transformation of five other types of rodent fibroblasts. We also investigated the effect of TGF alpha expression on the growth of BALB/MK mouse keratinocytes, which require epidermal growth factor (EGF) for proliferation. We show that exogenously added TGF alpha is an extremely potent mitogen for BALB/MK cells. However, retroviral expression of TGF alpha in BALB/MK cells failed to relieve dependence on exogenously added EGF (or TGF alpha) for cell growth. These results suggest that overexpression of TGF alpha does not, by itself, transform rodent fibroblasts or keratinocytes. .A Finzi E; Fleming T; Pierce JH. .I 275748 .U 91010890 .S J Invest Dermatol 9101; 95(4):388-92 .M Blotting, Western; Cells, Cultured; Epidermis/PA; Human; Immunohistochemistry; Keratin/*AN/IP; Keratosis/*PA; Male; Reference Values; Skin/CY/*PA; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Aberrant proliferation of lumen-forming cells in stratified epithelium of porokeratosis skin. .P JOURNAL ARTICLE. .W The present investigation was based on the postulate, first proposed by Reed and Leone in 1970, that porokeratosis lesions represent clonal growth of epidermal cells. Comparative studies using immunocytochemical staining, epidermal cell culture, and non-equilibrium pH gradient (NEpHG) gel electrophoresis analysis of the keratins extracted were carried out on five patients with various types of porokeratosis. Positive type IV collagen staining on the stratum corneum was found in lesional skin specimens of all patients, but not in normal controls. A search for connections between type IV collagen in the basement membrane of epidermis and the skin surface disclosed infrequent intra-epidermal streaking of type IV collagen and one positively stained trans-epidermal acrosyringium. Positive intra-epidermal laminin staining in porokeratosis lesions confirmed the trans-epidermal passage of basement-membrane materials. Epidermal cells cultured from lesional skin showed low plating efficiency, and all colonies exhibited intracytoplasmic vacuole formation and excessive top cell shedding. NEpHG gel electrophoresis of keratins extracted showed that lesional profiles not only contained keratins normally present in glabrous skin, but also possibly K9 and some additional proteins. K9 had been immunolocalized to periductal cells in previous studies. Our findings, taken together, strongly suggest that porokeratosis epidermis consists of epithelial cells with lumen-forming ability. .A Ma AS; Bell DJ; Dinneen AM. .I 275749 .U 91010891 .S J Invest Dermatol 9101; 95(4):393-6 .M Adolescence; Adult; Antibodies, Monoclonal/DU; Antigens, Surface/*AN; Epidermis/PA; Female; Hair/*PA; Human; Hyperhidrosis/*PA; Immunoenzyme Techniques; Keratinocytes/PA; Nuclear Proteins/*AN. .T The innermost cell layer of the outer root sheath is positive with Ki-67. .P JOURNAL ARTICLE. .W The expression of a cell proliferation-associated human nuclear antigen was immunohistochemically studied in human anagen hair and hair follicles using the monoclonal antibody Ki-67. The reaction of Ki-67 in mature anagen hair follicles was observed in the hair matrix cells and outer root sheath (ORS) cells. Nuclear staining was seen in a small number of matrix cells and in some ORS cells; this finding corresponded to the thymidine or bromodeoxyuridine labeling studies previously reported. In addition, there were two different patterns of cytoplasmic staining in the ORS: strong staining of the innermost cells (IMC) and weaker staining of the other ORS cells in the isthmus. Ki-67 reactivity of the IMC layer was observed at each stage of anagen and was regularly seen from the upper bulb to the isthmus. Ki-67 is a commercially available antibody that detects cycling cells. However, the IMCs in anagen hair follicles showed cytoplasmic labeling by Ki-67 from the matrix cells in the upper bulb to the distal portion of the isthmus. .A Miyauchi S; Hashimoto K; Miki Y. .I 275750 .U 91010892 .S J Invest Dermatol 9101; 95(4):397-402 .M Animal; Autoradiography; Cell Division/DE; DNA Replication/DE; Epidermal Growth Factor-Urogastrone/*PD; Epidermis/*CY/DE; Glycine/ME; Keratin/AN/BI; Kinetics; Organ Culture/MT; Rabbits; Skin/*CY/DE; Thymidine/ME; Time Factors; Tritium. .T Long-term organ culture of rabbit skin: effect of EGF on epidermal structure in vitro. .P JOURNAL ARTICLE. .W A method is described for maintaining the epidermal structure of normal rabbit ear skin explants in organ culture for up to 12 weeks. Split-thickness skin specimens were put in diffusion chambers made of either millipore filters or bovine collagen membranes, and then submitted to a roller tube culture at 15 rpm and 36 degrees C. The culture medium was Dulbecco's modified Eagle's medium (DMEM) supplemented with 20% fetal calf serum (FCS) + 0.4 micrograms/ml hydrocortisone. The gas used in the culture tube was air + 5% CO2. Autoradiography revealed the incorporation of [3H]-glycine into the 68-kD keratin band of explants for up to 12 weeks, indicating that normal keratinization was maintained throughout the entire culture period. The turnover time of the epidermis from basal layer to granular layer was around 7 d in both the early and late stages of culture. The addition of epidermal growth factor (EGF) to the culture caused the epidermis to become acanthotic with orthokeratosis, but with high concentrations of EGF (greater than or equal to 10 ng/ml) parakeratosis and increased proliferation of the epidermis occurred. Dexamethasone (DMS) strongly inhibited the EGF effect. .A Kondo S; Hozumi Y; Aso K. .I 275751 .U 91010893 .S J Invest Dermatol 9101; 95(4):403-8 .M Epidermis/CY/PH; Fourier Analysis; Human; Models, Biological; Skin/CY/*PH; Spectrophotometry, Infrared/MT; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Examination of stratum corneum barrier function in vivo by infrared spectroscopy. .P JOURNAL ARTICLE. .W It is generally accepted that the stratum corneum (SC) is the least permeable layer of the epidermis. Histologically, though, the SC is a non-uniform, inhomogeneous membrane, and the question "Is barrier function distributed uniformly across the SC thickness?" has been posed. To address this issue, human ventral forearm SC has been studied in vivo by attenuated-total-reflectance Fourier-transform infrared spectroscopy during the course of sequential tape-stripping. Because the intercellular lipids of the SC and the degree of hydration of the membrane have been shown to be crucial determinants of barrier function, attention has been focused on the spectral features, which report specifically on these parameters. The degree of disorder of the SC intercellular lipids has been found to decrease over the outer cell layers (up to three tape-strips) and then to remain essentially constant. The amount of lipids decreases similarly such that a 60% reduction (relative to the "no-strip" baseline) is observed after about four tape-strips. A plausible explanation for these measurements is that the lipids near the surface are a mixture of (a) "true" intercellular lipid (which is expected to be highly ordered), and (b) sebaceous lipid (which contains much greater amounts of low-melting components, such as fatty acids). The sequential infrared (IR) spectra provide at least circumstantial evidence to support this hypothesis. As expected, the IR spectra show that SC hydration increases from the surface towards the SC-stratum granulosum interface. Taken together, the results imply that the SC is indeed non-uniform. The properties of the outer layers (those removed by the first 3-4 tape-strips) change significantly with increasing depth.(ABSTRACT TRUNCATED AT 250 WORDS) .A Bommannan D; Potts RO; Guy RH. .I 275752 .U 91010894 .S J Invest Dermatol 9101; 95(4):409-14 .M Adult; Air; Antibodies, Monoclonal; Cell Differentiation/*; Cells, Cultured; Culture Media; Epidermis/*CY/UL; Fluorescent Antibody Technique; Human; Intermediate Filament Proteins/AN; Keratin/AN; Keratinocytes/*CY/UL; Microscopy, Electron; Protein Precursors/AN; Protein-Glutamine Gamma-Glutamyltransferase/AN. .T Terminal epidermal differentiation of human keratinocytes grown in chemically defined medium on inert filter substrates at the air-liquid interface. .P JOURNAL ARTICLE. .W A fully differentiated epithelium having the features of epidermis was obtained in vitro by culturing second-passage normal human keratinocytes (NHK) in the chemically defined medium MCDB 153 on inert filter substrates at the air-liquid interface for 14 d. Vertical sections stained for histology and indirect immunofluorescence studies show a correct stratification and expression of differentiation markers. The presence of desmosomes, keratohyalin granules, and lamellar granules, and the formation of a more than ten-layers stratum corneum was evidenced by electron microscopy. Moreover, lipids typical for differentiated epidermis were present in these cultures, including ceramides, which are thought to be responsible for the relative impermeability of the stratum corneum. Under our culture conditions, i.e., in defined medium and at the air-liquid interface, the use of de-epidermized dermis as a substrate did not stimulate keratinocyte differentiation more than acetate cellulose or polycarbonate filter membrane substrates. The obtaining of a well-differentiated epidermis grown in vitro on inert filters in a chemically defined medium should be useful as a standard system for studying epidermal differentiation, re-epidermization, cytotoxicity, epidermal permeation, and transepidermal drug delivery. .A Rosdy M; Clauss LC. .I 275753 .U 91010895 .S J Invest Dermatol 9101; 95(4):415-21 .M Animal; Antigens/AN; Biopsy; Cell Adhesion; Endothelium, Vascular/PA/*PP; Factor VII/AN/IM; Immunoenzyme Techniques; Kinetics; Leukocytes, Mononuclear/*PH; Lymphocytes/PH; Rats; Rats, Inbred Strains; Skin/*IN/PA/PP; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Swine; Time Factors; Wound Healing/*; Wounds and Injuries/PA/*PP. .T Recruitment of mononuclear cells by endothelial cell binding into wounded skin is a selective, time-dependent process with defined molecular interactions. .P JOURNAL ARTICLE. .W Wound healing involves a complex series of interactions between cells in the dermis and epidermis, and important relationships exist between keratinocytes and resident dermal cells. Monocytes and lymphocytes secrete cytokines that are capable of stimulating dermal repair and influencing keratinocyte and fibroblast migration and proliferation, although the mechanism by which mononuclear cells are recruited into the wound is unknown. We have tested the hypothesis that in wounded skin specialized endothelial cells are induced to mediate peripheral blood mononuclear cell (PBMC) emigration from the vasculature into the dermis. For this purpose, partial-thickness wounds made with a keratome on the backs of domestic pigs were excised 0 to 9, 12, 15, and 21 d after wounding. The biopsies were then tested for the capacity to adhere selectively to PBMC. The results indicated that PBMC overlaid onto sections of wounds from day 4 to 15 adhered selectively to dermal endothelium, with two distinct peaks of adherence observed on day 7 and day 12. In contrast, PBMC did not adhere to the tissue sections when overlaid onto frozen sections of normal skin or 0-, 1-, 2-, 3-, and 21-d-old wounded skin. Additional studies on the binding properties of PBMC subsets revealed that monocytes adhered maximally at day 7, whereas T cells adhered optimally at day 12 post-wounding. Furthermore, the adhesion process was energy and magnesium dependent but not calcium dependent and involved surface protein and carbohydrate moieties on PBMC surface. Pre-treatment of PBMC with monoclonal antibodies against the LFA-1 adhesive receptors inhibited the binding by greater than 80%, suggesting that LFA-1 adhesive receptors play an important role in the binding process. These studies provide evidence that the recruitment of monocytes and lymphocytes into wounds is an active, dynamic, and regulated process mediated at least in part by specific adhesive interactions between mononuclear leukocytes and dermal endothelial cells. .A Cai JP; Harris B; Falanga V; Eaglstein WH; Mertz PM; Chin YH. .I 275754 .U 91010896 .S J Invest Dermatol 9101; 95(4):422-7 .M Adult; Aged; Arterioles/PA/*UL; Epidermis/PA/UL; Female; Human; Male; Middle Age; Models, Structural; Reference Values; Skin/*BS/PA/UL; Support, U.S. Gov't, P.H.S.; Telangiectasia, Hereditary Hemorrhagic/*PA; Venules/PA/*UL. .T Ultrastructure and three-dimensional organization of the telangiectases of hereditary hemorrhagic telangiectasia. .P JOURNAL ARTICLE. .W We studied 10 cutaneous telangiectatic lesions of hereditary hemorrhagic telangiectasia (HHT), ranging in size from pinpoint to 2 mm, by light and electron microscopy. Four representative lesions were reconstructed by computer from serial 1- or 2-mm plastic embedded sections. The earliest clinically detectable lesion of HHT is a focal dilatation of postcapillary venules, which continue to enlarge and eventually connect with dilated arterioles through capillaries. As the vascular lesion increases in size, the capillary segments disappear and a direct arterio-venous communication is formed. This entire sequence of morphologic events is associated with a perivascular mononuclear cell infiltrate in which the majority of cells are lymphocytes and the minority are monocytes/macrophages by ultrastructure. Comparison of these findings with the telangiectatic mats of scleroderma and cherry angiomas revealed that the former, previously shown to be composed of dilated postcapillary venules, are also associated with perivascular infiltrates, but the latter, which are produced by capillary loop aneurysms, are not. .A Braverman IM; Keh A; Jacobson BS. .I 275755 .U 91010897 .S J Invest Dermatol 9101; 95(4):428-35 .M Adult; Biopsy; Diglycerides/*ME; Epidermis/CY/*EN/PA; Human; Kinetics; Phosphoinositides/*ME; Phospholipase C/*ME; Protease Inhibitors/PD; Psoriasis/*EN/PA; Reference Values; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tetradecanoylphorbol Acetate/PD. .T Increased phospholipase C-catalyzed hydrolysis of phosphatidylinositol-4,5-bisphosphate and 1,2-sn-diacylglycerol content in psoriatic involved compared to uninvolved and normal epidermis. .P JOURNAL ARTICLE. .W Evidence suggests that the phospholipase C/protein kinase C signal transduction system participates in the regulation of epidermal cell growth and differentiation. Psoriatic epidermis is characterized by hyperproliferation, defective differentiation, and inflammation. In this report, we have determined the activity of phospholipase C-catalyzed hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) and 1,2-diacylglycerol content in normal and psoriatic involved and uninvolved epidermis. 1,2-diacylglycerol is formed from phospholipase C-catalyzed hydrolysis of PIP2 and is the physiologic activator of protein kinase C. PIP2 hydrolysis was assayed in soluble and particulate fractions prepared from keratome biopsies of normal and psoriatic skin. Total lipids were extracted from normal and psoriatic epidermis and 1,2-diradylglycerol (a mixture of 1,2-diacylglycerol and 1-ether, 2-acyl-glycerol) quantitated by enzyme assay. Because 1,2-diacylglycerol is a more potent activator of protein kinase C, the relative proportions of 1,2-diacyl and 1-ether, 2-acylglycerol in uninvolved and involved psoriatic epidermis were determined. This was accomplished by separation of acetate derivatives of 1,2-diacylglycerol and 1-ether, 2-acyl-glycerol by thin layer chromatography. Soluble and membrane-associated phospholipase C-catalyzed PIP2 hydrolysis were increased 3.7 times (p less than 0.001) and 3 times (p less than 0.004), respectively, in psoriatic involved compared to uninvolved and normal epidermis. 1,2-diradylglycerol content was also significantly elevated (3 times, p less than 0.01) in psoriatic involved versus uninvolved and normal epidermis. Analysis of the acetate derivatives of 1,2-diradylglycerol in psoriatic uninvolved and involved epidermis revealed that 1,2-diacylglycerol was the major species (86% and 95%, respectively). There were no significant differences in either phospholipase C-catalyzed PIP2 hydrolysis or 1,2-diacylglycerol content between uninvolved and normal epidermis. 1,2-diacylglycerol purified from normal and involved psoriatic epidermis was capable of activating protein kinase C from normal epidermis in vitro. In epidermal slices, activation of protein kinase C by addition of 12-0-tetradecanoylphorbol-13-acetate and 1,2-diacylglycerol (1,2-dioctanoylglycerol) resulted in subsequently decreased protein kinase C activity, a process termed down-regulation. These data are consistent with the possibility that the elevation in lesional 1,2-diacylglycerol content may account, in part, for the previously reported reduction of protein kinase C activity in psoriasis (Horn, Marks, Fisher, et al: J Invest Dermatol 88:220-222, 1987). .A Fisher GJ; Talwar HS; Baldassare JJ; Henderson PA; Voorhees JJ. .I 275756 .U 91010899 .S J Invest Dermatol 9101; 95(4):441-5 .M Adult; Biopsy; Calcium/PD; Catalase/PD; Cell Division/DE; Cells, Cultured; Cholera Toxin/PD; Culture Media; Growth Substances/PD; Human; Melanocytes/*CY/DE/PA; Reference Values; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tetradecanoylphorbol Acetate/PD; Tissue Culture/MT; Vitiligo/*PA; 1-Methyl-3-Isobutylxanthine/PD. .T Successful culture of adult human melanocytes obtained from normal and vitiligo donors. .P JOURNAL ARTICLE. .W The development of growth conditions for human melanocytes from uninvolved skin from vitiligo patients and age-matched normal adults is a prerequisite to understanding the etiology of this pigmentary disorder. By using new growth conditions, pure melanocyte cultures were prepared from normal adults and the pigmented skin of vitiligo donors. Both cell types grew without a lag period and were maintained for more than six months (4-8 passages). The cultures could be expanded from several thousand melanocytes in the original cell suspension to several million cells (2-7 x 10(6] in pure culture. To obtain these results, the current standard conditions for the culture of fetal melanocytes were substantially modified. MEM-S medium was less satisfactory than MCDB-153. Adult normal and vitiligo cells also required the presence of exogenous catalase (20 micrograms/ml) during isolation and primary seeding. Thereafter, this enzyme was not necessary. Melanocytes grew best and gave the highest yields if the concentrations of both calcium (200 microM) and the phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA) were low (4-8 nM). Other growth factors included in the MCDB-153 media were bFGF, crude bovine pituitary extract, insulin, transferrin, hydrocortisone, 5% FCS, and the antioxidant alpha-tocopherol. Cholera toxin and isobutylmethylxanthine (IBMX) were omitted from the MCDB-153 growth medium because they slowed down growth even at very low concentrations. The results indicate adult and vitiligo melanocytes can be cultured. Preliminary studies of the normal and vitiligo cells indicate that vitiligo melanocytes retain some of the ultrastructural abnormalities observed in skin even when grown in culture. .A Medrano EE; Nordlund JJ. .I 275757 .U 91010900 .S J Invest Dermatol 9101; 95(4):446-9 .M Animal; Antigen-Presenting Cells/*IM; Cells, Cultured; Clone Cells; Female; Kinetics; Langerhans Cells/*IM; Mice; Mice, Inbred C3H; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; T-Lymphocytes/*IM; Time Factors. .T Delayed antigen presentation by epidermal Langerhans cells to cloned T h1 and T h2 cells [see comments] .P JOURNAL ARTICLE. .W Langerhans (LC) cells require incubation with protein antigen for several days before the cells effectively stimulate proliferation of cloned, H-2 restricted, antigen-specific T h cells. In contrast, splenic antigen-presenting cells are immediately effective. LC are immediately competent, however, if an immunogenic peptide rather than the intact protein is the immunogen, indicating that resident or unchallenged LC have the required class II MHC and can provide the signals necessary for T-cell proliferation but may lack the capacity to internalize or cleave protein antigens. We propose that delayed antigen presentation by LC may be intrinsic and advantageous for promoting early systemic immunity. LC stimulate cloned T h1 and T h2 cells equally well, suggesting that LC may not limit or bias the type of immunity that occurs with cutaneous antigenic challenge. .A Tiegs SL; Evavold BD; Yokoyama A; Stec S; Quintans J; Rowley D. .I 275758 .U 91010901 .S J Invest Dermatol 9101; 95(4):450-5 .M Antibodies, Monoclonal; Cells, Cultured; Electrophoresis, Gel, Two-Dimensional; Electrophoresis, Polyacrylamide Gel; Human; Immunoblotting; Keratin/*BI/IP; Keratinocytes/CY/DE/*ME; Tissue Culture/MT; Tretinoin/*PD. .T Effect of retinoids on hyperproliferation-associated keratins K6 and K16 in cultured human keratinocytes: a quantitative analysis. .P JOURNAL ARTICLE. .W The keratin patterns of human epidermal keratinocytes cultured on a 3T3-feeder layer in the presence of 10(-8) M non-aromatic (all-trans retinoic acid and 13-cis retinoic acid) and polyaromatic (arotinoid, arotinoid-sulfone, and free arotinoic-acid) retinoids were analyzed by high resolution one- and two-dimensional gel electrophoresis and immunoblotting. Laser densitometric evaluation of one-dimensional gels allowed to quantitate the changes within the keratin patterns and revealed an increase in the expression of keratins K13, K15, and K19 as induced by both non-aromatic and polyaromatic retinoids, except for the parent compound arotinoid. This would then indicate that such keratinocytes are pursuing a more embryonic type of differentiation. In evaluating the data for the hyperproliferation-associated keratins K6 and K16 we noticed an unexpected result: except for all-trans retinoic acid, these two keratins showed opposite responses. As compared to control cultures, the amount of K6 did generally increase, while K16 was reduced, with arotinoid acid being the most effective retinoid. The apparently uncoupled expression of K6 and K16 appeared also to be concentration dependent when 13-cis retinoic acid at concentrations of 10(-9), 10(-8), and 10(-7) M was analyzed. Considering the overall antiproliferative potency of retinoids, we therefore conclude that K16 alone, rather than the pair K6/K16, should be regarded as a proliferation-related keratin and as such may be used as a sensitive marker to evaluate keratinocyte proliferation. .A Korge B; Stadler R; Mischke D. .I 275759 .U 91010903 .S J Invest Dermatol 9101; 95(4):460-500 .M Human; Skin Diseases/*. .T Abstracts for the 20th annual meeting of the European Society for Dermatological Research. Turin, Italy, June 9-12, 1990. .P MEETING REPORT; OVERALL. .I 275760 .U 91011120 .S J Lab Clin Med 9101; 116(4):423-7 .M History of Medicine, 20th Cent.; Research; Societies, Medical/*HI; United States. .T A history of the Central Society for Clinical Research [editorial] .P EDITORIAL; HISTORICAL ARTICLE. .A Levin ML. .I 275761 .U 91011121 .S J Lab Clin Med 9101; 116(4):428 .M Antiviral Agents/*PD; Blood Proteins/ME; Blood Transfusion; Human; HIV-1/*DE; HTLV-I/*DE; Light; Pyrimidinones/*PD; Radiation-Sensitizing Agents/*PD. .T Photosensitization of viral particles [editorial; comment] .P COMMENT; EDITORIAL. .A Kessel D. .I 275762 .U 91011122 .S J Lab Clin Med 9101; 116(4):429-38 .M Animal; Endothelium, Vascular/DE/PH; Gene Expression Regulation; Human; Inflammation; Recombinant Proteins/PD; Shock, Septic/*PP; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tumor Necrosis Factor/GE/PD/*PH. .T Regulation of the pathophysiology of tumor necrosis factor. .P JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC. .A DeForge LE; Nguyen DT; Kunkel SL; Remick DG. .I 275763 .U 91011123 .S J Lab Clin Med 9101; 116(4):439-47 .M Adenosine Triphosphate/BL; Adenoviruses, Human/*DE; Animal; Antiviral Agents/*PD; Blood Transfusion/*; Cell Line; Cytomegaloviruses/*DE; Diphosphoglyceric Acids/BL; Erythrocytes/*PH/RE; Herpesvirus hominis/*DE; Human; HTLV-I/*DE; In Vitro; Kinetics; Light; Pyrimidinones/*PD; Radiation-Sensitizing Agents/*PD; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Evaluation of merocyanine 540-sensitized photoirradiation as a means to inactivate enveloped viruses in blood products [see comments] .P JOURNAL ARTICLE. .W Dry or wet heat, solvents, and detergents combined with ultraviolet irradiation provide effective means of sterilizing soluble blood products such as albumin or factor VIII. For obvious reasons, these procedures are not applicable to cellular blood components. We have recently shown that simultaneous exposure to the photosensitizer, merocyanine 540 (MC 540) and white light rapidly inactivates the Friend erythroleukemia virus complex and Friend virus-transformed cells, but causes relatively little damage to pluripotent hematopoietic stem cells. In this communication, we show that several lipid-enveloped human pathogenic viruses are also highly susceptible to MC 540-sensitized photoirradiation, and we report on an initial evaluation of the ability of MC 540-sensitized photoirradiation to sterilize blood products. .A O'Brien JM; Montgomery RR; Burns WH; Gaffney DK; Sieber F. .I 275764 .U 91011124 .S J Lab Clin Med 9101; 116(4):448-56 .M Anemia, Sickle Cell/BL; Cell Separation/MT; Erythrocyte Deformability/*; Erythrocytes/*CY; Hematocrit; Human; Reference Values; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Isolation and quantitation of human erythrocyte deformability classes. .P JOURNAL ARTICLE. .W A new technique is described that fractionates erythrocytes according to their deformability. The method is a modification of the method of Beutler et al. (J Lab Clin Med 1976;88:328-33), in which small cellulose columns are used to remove white cells from blood samples. We find that when the length-to-width ratio of the columns is increased, the mixed cellulose bed also fractionates the red cells. Measurement of mean cell volume, mean corpuscular hemoglobin concentration, hemoglobin level, deformability index, and cell density showed that deformability is the physical property of the erythrocyte that forms the basis for the fractionation. This is a separation modality that complements the numerous density gradient techniques for red cells. The following experimental results can be obtained by using the technique: (1) The number of cells with a defined degree of rigidity can be quantitated in an erythrocyte population. (2) Large numbers of cells that differ with respect to their deformability can be isolated. (3) Application of the method to sickle cells has quantitated the remarkable heterogeneity of these cells with regard to their deformability. .A Acquaye C; Johnson RM. .I 275765 .U 91011125 .S J Lab Clin Med 9101; 116(4):457-61 .M Biological Markers/*BL; Carcinoma, Non-Small Cell Lung/BL/*IM/PA; Carcinoma, Oat Cell/BL/*IM/PA; Comparative Study; Female; Human; Lactate Dehydrogenase/BL; Lung Neoplasms/BL/*IM/PA; Male; Neoplasm Staging; Prognosis; Receptors, Interleukin-2/*AN; Reference Values. .T Elevated serum levels of soluble interleukin-2 receptors in small cell lung carcinoma. .P JOURNAL ARTICLE. .W The presence of the soluble form of the interleukin-2 receptors (sIL-2R) was evaluated in the serum of 21 patients with small cell lung carcinoma (SCLC) and 37 patients with non-small cell lung carcinoma (non-SCLC) by means of an enzyme-linked immunosorbent assay. The sIL-2R level was measured serially in patients with SCLC both during and after therapy. The mean serum level of sIL-2R in patients with SCLC was 3.8 times higher than that of 47 healthy controls and was 1.9 times higher than in 37 patients with non-SCLC. Six patients with SCLC had very high levels of sIL-2R, ranging from five to 52 times the mean level observed in normal controls. Tumor cells in the pleural fluid of the patient with highest levels were positive with monoclonal antibodies to IL-2R (CD25), NKH-1, OKDR, and OKT9. A longitudinal study in this patient showed a good correlation between tumor activity and sIL-2R levels. Also, the sIL-2R levels decreased in patients responding to therapy. These results suggest that some SCLCs secrete sIL-2R and that the serial measurements of the serum sIL-2R levels can be used as a noninvasive tumor marker in this disease. .A Yamaguchi K; Nishimura Y; Kiyokawa T; Matsuzaki H; Ishii T; Kubota K; Kawahara M; Furuse K; Yoshinaga T; Kinuwaki E; et al. .I 275766 .U 91011126 .S J Lab Clin Med 9101; 116(4):462-8 .M Captopril/*PD; Comparative Study; Drug Interactions; Female; Glomerular Filtration Rate/DE; Human; Ibuprofen/*PD; IgG/UR; Male; Nephrosis/*UR; Proteinuria/*; Renal Circulation/DE. .T Acute effects of captopril and ibuprofen on proteinuria in patients with nephrosis. .P JOURNAL ARTICLE. .W Captopril decreases protein excretion in patients with nephrosis. To evaluate whether captopril has an acute antiproteinuric effect and to evaluate the role of changes in renal hemodynamics or glomerular permselectivity on this effect, renal clearance studies were performed in patients without diabetes but with nephrosis. Protein excretion and renal hemodynamics were measured at baseline and after the administration of captopril. To measure the contribution of renal prostaglandins, patients were restudied on a separate day, after the combined administration of captopril and the prostaglandin synthetase inhibitor ibuprofen. Both treatments significantly reduced mean protein excretion, but the change was greater with combined therapy than with captopril alone (40.6% vs 20.0%). Mean glomerular filtration rate (GFR) decreased by 4.8% (not significant) and 16.5% (p less than 0.001), and filtration fraction (FF) decreased by 13.6% (p less than 0.001) and 14.9% (p less than 0.001) after captopril alone and combined therapy, respectively. No significant correlation was found between changes in proteinuria and changes in GFR or FF after treatment with captopril alone. In contrast, the decrease in proteinuria correlated with the change in GFR after combined drug administration (r = 0.68, p = 0.06). The ratio of immunoglobulin G to albumin clearance, an index of glomerular permselectivity, was unaffected by captopril but decreased significantly (by 43%) after combined drug administration. The results suggest that the acute antiproteinuric effect of captopril is not due to changes in FF, GFR, or glomerular perselectivity. The addition of ibuprofen enhances the antiproteinuric effect of captopril by decreasing the GFR as well as by enhancing the permselectivity of the glomerular capillary membrane. .A Allon M; Pasque CB; Rodriguez M. .I 275767 .U 91011127 .S J Lab Clin Med 9101; 116(4):469-78 .M Albuminuria/*; Animal; Blood Glucose/ME; Diabetes Mellitus, Experimental/BL/PP/*UR; Dinoprostone/UR; Female; Glomerular Filtration Rate/DE; Imidazoles/*PD; Proteinuria; Rats; Rats, Inbred Strains; Reference Values; Serum Albumin/ME; Support, U.S. Gov't, P.H.S.; Thromboxane B2/*UR; Thromboxanes/*AI. .T Suppression of urinary albumin excretion in diabetic rats by 4'(imidazol-1-yl) acetophenone, a selective inhibitor of thromboxane synthesis. .P JOURNAL ARTICLE. .W Thromboxane contributes to the regulation of glomerular hemodynamics in experimental models of diabetes and has been implicated as mediator in some models of glomerular injury. In the present study we examined urinary albumin, protein, and thromboxane B2 (TXB2) excretion during the 170 days after induction of diabetes by injection of streptozotocin in insulin-treated moderately hyperglycemic (200 to 400 mg/dl glucose) rats (SDRs). The effects of a thromboxane synthesis inhibitor, 4'-(imidazol-1-yl)acetophenone (TXI) (100 mg/kg/day) on these parameters were also assessed. Urinary TXB2 and albumin excretion in SDRs was not different from that in normal rats between 7 and 90 days but were three times higher than normal in SDRs at 125 and 170 days after induction of diabetes. In SDRs, urinary protein excretion was higher than in controls at 170 days but not at earlier time points. Inulin clearance (CIn) of SDRs was significantly higher than control values at 7 and 90 days and was not influenced by TXI during this period. At 170 days CIn was not significantly different in SDRs and normal rats. By contrast, albumin clearance (CAIb) and fractional CAIb were elevated in SDRs when compared with those values in normal rats. Treatment of SDRs with TXI for 170 days completely prevented the rise in urinary TXB2, albumin, and protein excretion, as well as the rise in fractional CAIb, but did not alter prostaglandin E2 (PGE2) excretion. TXI also increased CIn in SDRs to levels that were significantly higher than normal at 170 days. TXI had no significant effect on urinary PGE2, TXB2, albumin, or protein excretion or on CIn in normal rats and did not influence blood pressure or blood glucose in normal rats or SDRs. The results suggest a role for thromboxane in the mediation of albuminuria in the SDR. .A Craven PA; DeRubertis FR. .I 275768 .U 91011128 .S J Lab Clin Med 9101; 116(4):479-86 .M Adult; Aged; Blood Platelets/*IM; Comparative Study; Enzyme-Linked Immunosorbent Assay; Flow Cytometry/MT; Human; HIV Seropositivity/*; IgG/*AN; IgM/*AN; Immunoglobulins, Surface/*AN; Middle Age; Platelet Count; Reference Values; Substance Abuse/BL/IM; Support, Non-U.S. Gov't. .T Assessment of platelet antibody by flow cytometric and ELISA techniques: a comparison study. .P JOURNAL ARTICLE. .W Two different methods for evaluating platelet antibody were used to study 12 normal subjects and 24 patients consisting primarily of intravenous drug users (IVDUs) who were positive for human immunodeficiency virus (HIV). Total platelet-associated immunoglobulin G (IgG) and immunoglobulin M (IgM) were measured by enzyme-lined immunosorbent assay on platelet lysate, and platelet surface-associated IgG and IgM were measured by semiquantitative flow cytometry. IgG and IgM values showed significant correlations between the two measurement methods. Mean platelet surface IgG and total IgG were 3.6 and 4.3 times greater, respectively, in IVDUs than in controls, and platelet IgM was also significantly higher in IVDUs than in controls as measured by both techniques. Although mean platelet immunoglobulin levels were higher in the IVDUs with thrombocytopenia than in IVDUs with normal platelet counts, these differences did not achieve significance. These data show that platelet IgG and IgM levels are increased in IVDU-associated HIV infection and suggest that these increases are not confined to patients manifesting thrombocytopenia. The herein described platelet surface antibody and total platelet antibody measurements appear to be equally useful in studying this patient population. Specific details for generating platelet-associated immunofluorescence units are discussed. .A Lin RY; Levin M; Nygren EN; Norman A; Lorenzana FG. .I 275769 .U 91011130 .S J Lab Clin Med 9101; 116(4):492-7 .M Autoantibodies/IM; Base Sequence; Chromosome Deletion/*; DNA/*GE; Exons; Factor IX/*GE/IM; Genes, Structural/*; Hemophilia/*GE; Human; Introns; Molecular Sequence Data; Mutation/*; Oligonucleotide Probes; Polymerase Chain Reaction; Support, Non-U.S. Gov't. .T DNA sequence analysis of three inhibitor-positive hemophilia B patients without gross gene deletion: identification of four novel mutations in factor IX gene. .P JOURNAL ARTICLE. .W Three hemophilia B patients with anti-factor IX antibodies who had no detectable gross deletion of the factor IX gene by Southern blotting analysis were investigated at the molecular level. All eight exons, accompanied by their splicing junction sites and presumptive promoter regions of the factor IX gene in these patients (total 5.5 kb in length) were amplified with the use of the polymerase chain reaction, followed by complete nucleotide sequence analysis. Three different types of novel single base substitutions and a 2 base-pair nucleotide deletion were identified. Patient HB-5 had two point mutations in his factor IX gene. One was located at the promoter region at nucleotide -793 and the other (C-to-T transition) was found in exon VI of the gene changing Gln-191 to a stop codon. Patient HB-6 had a point mutation (G-to-A) in the splice acceptor site, which interrupted the normal splicing of the last intron G. A small two-nucleotide deletion in exon III was detected in patient HB-7 and yielded frameshifted amino acids and terminated by a stop codon. These resuslts suggest that not only the gross gene deletion of factor IX gene but also the point mutations or small nucleotide deletion that may cause the interruption of coding informations for mature protein synthesis is predisposed to development of anti-factor IX inhibitors in patients with hemophilia B. .A Matsushita T; Tanimoto M; Yamamoto K; Sugiura I; Hamaguchi M; Takamatsu J; Kamiya T; Saito H. .I 275770 .U 91011131 .S J Lab Clin Med 9101; 116(4):498-507 .M Anemia/BL/CI/*IM; Animal; Dinoprostone/BL; Erythrocyte Count; Hematocrit; IgG/*AN; IgM/*AN; Immunization, Passive; Leukocyte Count; Lymphocyte Transformation/*; Male; Phenylhydrazines; Rats; Reference Values; Support, Non-U.S. Gov't. .T Immune activation is associated with phenylhydrazine-induced anemia in the rat. .P JOURNAL ARTICLE. .W Long-term phenylhydrazine (PHZ) treatment caused pronounced anemia and a concomitant increase in the numbers of circulating leukocytes in Long-Evans rats. The leukocytosis was caused mainly by an elevation in mononuclear cells, most notably in the lymphocyte population. PHZ has been reported to cause the direct lysis of erythrocytes by nonimmune mechanisms. However, recent reports indicate that PHZ can cross-link red cell band 3 protein (senescent antigen), resulting in the binding of autologous immunoglobulin G (IgG). Recognition of this complex by macrophage Fc receptor mechanisms triggers rapid erythrophagocytosis-in the spleen and possibly the liver as well. In our study, analysis of the blood, bone marrow, and spleen cells of long-term (1 to 6 weeks) PHZ-treated rats was performed by using flow cytometry. Total serum IgG levels were determined by radial immunodiffusion, and antibodies reactive with red cells that were sensitized to PHZ either in vivo or in vitro were titered by using the indirect Coombs' method. Serum prostaglandin E2 titers also were determined at different time intervals after PHZ administration. The results indicate that PHZ induces an increase in circulating antibody and prostaglandin E2 titers that correlates with the onset of anemia and that the serum of PHZ-treated rats can induce anemia in normal recipients after passive transfer. Cytofluorographic studies revealed a marked increase in the B-cell population of the peripheral blood and spleen and an altered ratio T-helper to T-suppressor cells at certain time intervals after PHZ injection. The results indicate that in addition to inducing senescence-like alterations in erythrocyte membrane proteins, PHZ stimulates the production of the autologous IgG that recognizes these sites and promotes lymphoid blastogenesis, most notably in the B-cell lineage. .A Naughton BA; Dornfest BS; Bush ME; Carlson CA; Lapin DM. .I 275771 .U 91011132 .S J Lab Clin Med 9101; 116(4):508-15 .M Basement Membrane/IM; Case Report; Collagen/AN; Female; Glomerulonephritis/*IM/PA; Human; HLA Antigens/AN; Kidney Glomerulus/*IM; Kidney Transplantation/*IM/PA; Male; Nephritis, Hereditary/*GE/IM/SU; Pedigree; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Posttransplant anti-glomerular basement membrane nephritis in related males with Alport syndrome. .P JOURNAL ARTICLE. .W This report describes the development of anti-glomerular basement membrane (GBM) glomerulonephritis after kidney transplantation in related males with Alport syndrome. Antibodies in sera from one of these patients stained normal GBM, Bowman's capsule, tubular basement membranes, and epidermal basement membranes but did not stain tissues from an unrelated Alport male. The target antigen was found to be a 26 kd peptide of the noncollagenous domain of basement membrane collagen. This study provides further evidence of the importance of abnormalities of basement membrane collagen in the pathogenesis of the Alport nephropathy. We speculate that certain mutations at the Alport locus, such as large intragenic deletions or frame-shift mutations, may be associated with failure to develop immune tolerance to epitopes on this 26kd peptide. In the setting of permissive immune response and regulation, transplantation of a normal kidney may result in the generation of anti-GBM antibodies. .A Kashtan CE; Butkowski RJ; Kleppel MM; First MR; Michael AF. .I 275772 .U 91011133 .S J Lab Clin Med 9101; 116(4):516-26 .M Amino Acid Sequence; Blood Coagulation Factors/*GE/IP/ME; Chromatography, Affinity; Comparative Study; Connective Tissue/*ME; Glucose/AN; Glycosylation; Human; In Vitro; Isoelectric Focusing; Kinetics; Molecular Sequence Data; Pancreatopeptidase/ME; Protein Conformation; Protein Processing, Post-Translational/*; Sequence Homology, Nucleic Acid; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Connective tissue activation. XXXIV: Effects of proteolytic processing on the biologic activities of CTAP-III. .P JOURNAL ARTICLE. .W Microheterogeneity of connective tissue activation peptide III (CTAP-III) was revealed by preparative and analytical isoelectric focusing. Proteolytic activities in human platelet preparations resulted in four cleavage products of platelet-derived CTAP-III. Three isoforms (CTAP-III des 1-13, des 1-14, and des 1-15/NAP-2) stimulate [14C]glycosaminoglycan synthesis; two isoforms also promote [3H]DNA synthesis in human fibroblast cultures. Elastase (from porcine pancreas) cleavage of human platelet-derived CTAP-III and rCTAP-III-Leu-21 to the des 1-15 isoforms was associated with either preservation of specific anabolic biologic activity or an actual increase in specific activity. Nonenzymatic glycosylation of lysyl residues and deamination of the NH2-terminal asparagine of platelet-derived CTAP-III were commonly present, but did not correlate with the biologic activities that were measured. Protein sequence homology shows CTAP-III and its isoforms to be members of a family of proteins (including NAP-1/II-8, MGSA, and platelet factor-4) known to be associated with growth, wound repair, inflammation, and neoplasia. The consequences of proteolytic processing reported here for CTAP-III may be characteristic of the other proteins in this group. .A Castor CW; Walz DA; Johnson PH; Hossler PA; Smith EM; Bignall MC; Aaron BP; Underhill P; Lazar JM; Hudson DH; et al. .I 275773 .U 91011134 .S J Lab Clin Med 9101; 116(4):527-34 .M Amino Acid Sequence; Antibodies; Antigenic Determinants/*AN; Erythrocytes/IM; Ficin; Glycophorin/*IM; Hemagglutination Inhibition Tests; Human; Molecular Sequence Data; MNSs Blood-Group System/*IM; Neuraminidase; Oligopeptides/CS; Support, U.S. Gov't, P.H.S.. .T Octapeptide segments from the amino terminus of glycophorin A contain the antigenic determinants of the M and N blood groups systems. .P JOURNAL ARTICLE. .W Human red blood cells with phenotype N/N and M/M were tested in an agglutination assay with anti-N and anti-M antibodies, respectively. After incubation of the synthesized octapeptide (Leu-Ser-Thr-Thr-Glu-Val-Ala-Met) from the N-amino terminus of glycophorin A, with anti-N antibody, there was significant inhibition of the agglutination of the N-positive cells. There was also inhibition of the agglutination of the M-positive cells with anti-M antibody by the synthesized octapeptide (Ser-Ser-Thr-Thr-Gly-Val-Ala-Met) from the M-amino terminus of glycophorin A. There was no inhibition, however, of the agglutination of M-positive cells with anti-M antibodies by the N-amino terminal octapeptide. Likewise, the M-amino terminal octapeptide did not inhibit agglutination of N-positive cells with anti-N. Because the synthesized octapeptides contained no carbohydrate, the anti-N and anti-M specificity appears to be determined principally by the peptides themselves. Further studies with the use of chimeric peptides indicate that the amino terminal amino acid leucine of N-glycophorin A is a primary determinant of the N antigen, whereas the amino terminal serine of M-glycophorin A is a primary determinant for the M antigen. .A Pedersen JT; Kaplan H; Wedeck L; Murphy RB; LoBue J; Pincus MR. .I 275774 .U 91011135 .S J Lab Clin Med 9101; 116(4):535-45 .M Erythrocyte Deformability/*; Erythrocyte Membrane/PH; Erythrocytes/DE/*PH; Hematocrit; Hemolysis; Human; Hydrogen Peroxide/PD; Osmolar Concentration; Peroxides/*PD; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Viscosity. .T Use of ektacytometry to determine red cell susceptibility to oxidative stress. .P JOURNAL ARTICLE. .W To define a more sensitive and reliable method to determine changes in the overall cellular characteristics of erythrocytes after oxidative damage, we used a viscodiffractometric method (ektacytometry) to measure the effect of oxidative stress. Erythrocytes were incubated in the presence of hydrogen peroxide, t-butyl hydroperoxide, or cumene hydroperoxide in phosphate buffer. This treatment resulted in decreased cellular deformability of the intact erythrocytes. In addition, deformability and fragility measurements of the erythrocyte ghost membranes indicated an increased membrane dynamic rigidity and altered-mechanical stability as a consequence of oxidant stress. These changes were observed before the onset of hemolysis. The observed decrease in deformability was accompanied by oxidation of hemoglobin, alterations of membrane proteins, and lipid peroxidation. To continuously measure the time course of the decrease in deformability in intact erythrocytes under oxidative stress, a new ektacytometric method was developed. Erythrocytes were oxidatively challenged within the viscometer at a constant osmolality and shear stress. The change in deformability was monitored and a typical range was defined for erythrocytes from normal individuals. Comparison of erythrocytes from patients with sickle cell disease with those from normal individuals demonstrated a higher susceptibility of sickle red cells toward oxidative stress. .A Kuypers FA; Scott MD; Schott MA; Lubin B; Chiu DT. .I 275775 .U 91011137 .S J Lab Clin Med 9101; 116(4):555-62 .M Adult; Aged; Chromatography, Gel; Female; Hepatitis B Antibodies/*AN; Hepatoma/*BL; Human; Insulin-Like Growth Factor I/*ME; Insulin-Like Growth Factor II/*GE/IP/*ME; Liver Neoplasms/*BL; Male; Middle Age; Protein Precursors/*GE; Protein Processing, Post-Translational/*; Radioimmunoassay; Reference Values; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Abnormal processing of pro-IGF-II in patients with hepatoma and in some hepatitis B virus antibody-positive asymptomatic individuals. .P JOURNAL ARTICLE. .W Hepatomas are a common malignancy in countries with a high prevalence of hepatitis B virus infections. These tumors may present with severe persistent hypoglycemia. We have studied the possible relationship of production of insulin-like growth factor II (IGF-II) by these tumors and the development of hypoglycemia. Mean IGF-II concentration was not significantly higher in 23 patients with hypoglycemia than in nine patients with euglycemia (542 +/- 61 [SE] micrograms/L vs 382 +/- 52 micrograms/L). Serum IGF-I was more suppressed in patients with hypoglycemia (16 +/- 3 micrograms/L) than in patients with euglycemia (57 +/- 18 micrograms/L). Because an increased percentage of IGF-II in serum of patients with hypoglycemia who have other tumors is present as partially processed pro-IGF-II ("big" IGF-II), we passed sera of patients with hypoglycemia and patients with euglycemia with hepatomas through acidic Bio-Gel P-60 columns. We found that 57% +/- 4.6% of the IGF-II in sera from patients with hypoglycemia was present as big IGF-II compared with 22% +/- 3% in patients with euglycemia with hepatomas (not significantly different from that in normal controls). Four of 11 apparently healthy control subjects who were hepatitis B virus positive also had increased percentages of big IGF-II, suggesting that abnormal processing of pro-IGF-II may result from subtle changes in liver function with this infection. It remains to be determined whether these subjects with increased big IGF-II are at increased risk for the development of hepatomas. In conclusion, we have confirmed marked suppression of IGF-I in the sera of patients with hepatoma and hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS) .A Daughaday WH; Wu JC; Lee SD; Kapadia M. .I 275776 .U 91011138 .S J Lab Clin Med 9101; 116(4):563-72 .M History of Medicine, 20th Cent.; Periodicals; Research; Societies, Medical/*HI; United States. .T Origins and early days of the Central Society for Clinical Research. 1977 [classical article] .P CLASSICAL ARTICLE; HISTORICAL ARTICLE; HISTORICAL BIOGRAPHY; JOURNAL ARTICLE. .A Bean WB. .I 275777 .U 91011139 .S J Lab Clin Med 9101; 116(4):573-4 .M Adult; Child; Chromosome Deletion/*; Erythrocyte Volume/*; Erythrocytes/*PH; Female; Genotype; Globin/*GE; Hemoglobinopathies/BL/*GE; Hemoglobins/*ME; Human; Male; Reference Values. .T The effect of alpha-hemoglobin gene deletions on the red blood cells' mean cell volume and hemoglobin levels [letter] .P LETTER. .A Thompson CC; Houston DS; Boyadjian S; Ali MA. .I 275778 .U 91011284 .S J Fam Pract 9101; 31(4):353 .M Family Practice/*; Human; Models, Biological/*; Models, Psychological/*. .T The biopyschosocial model [letter] .P LETTER. .A Dozor R. .I 275779 .U 91011285 .S J Fam Pract 9101; 31(4):353, 356 .M Chlamydia trachomatis/*; Chlamydia Infections/*MI/TH; Female; Fluorescent Antibody Technique; Genital Diseases, Female/*MI/TH; Human; Male. .T Genital chlamydia infection [letter; comment] .P COMMENT; LETTER. .A Saxer JJ. .I 275780 .U 91011286 .S J Fam Pract 9101; 31(4):356 .M Case Report; Child; Child Abuse, Sexual/*CO; Female; Human; Male; Urticaria/*ET. .T Child sexual abuse and the skin [letter] .P LETTER. .A Marley J. .I 275781 .U 91011287 .S J Fam Pract 9101; 31(4):357-8 .M Depression/*CO; Headache/*CO; Human. .T Headache and depression [editorial; comment] .P COMMENT; EDITORIAL. .A Smith R. .I 275782 .U 91011288 .S J Fam Pract 9101; 31(4):360-4 .M Adolescence; Adult; Aged; Depression/*CO/EP; Family Practice; Female; Headache/*CO; Human; Male; Middle Age; Prevalence; Psychological Tests; Recurrence; Self Assessment (Psychology). .T Headache: a marker of depression [see comments] .P JOURNAL ARTICLE. .W Patients who presented with a chief complaint of headache in the outpatient family practice setting were found to have a high prevalence of depression (63%) by the Zung Self-Rating Depression Scale (SDS) index. A statistically significant relationship was found between the frequency of headaches (P = .03) with level of depression. In fact, 74% of patients with headaches recurring almost every day had a clinically significant depression diagnosed as defined by the Zung SDS score. The Zung SDS score also correlated with the length of time that the problem of headache existed (P less than .05). Item analysis of the individual 20-item depression score revealed that four questions accounted for 93% of the variance. This analysis suggests that shorter, more abbreviated screening questions could be developed and refined in the future for use by the busy clinician. Headache is an important marker for depression in the primary care setting. It can be inferred from this study that the clinician may need to focus more on treating the entity of depression than on treating just the symptom of headache. .A Chung MK; Kraybill DE. .I 275783 .U 91011289 .S J Fam Pract 9101; 31(4):365-8 .M Adult; Aged; Arizona/EP; Cholesterol/BL; Female; Hospital Bed Capacity, 300 to 499; Human; Hypercholesterolemia/EP/*PC; Life Style; Male; Mass Screening/*OG; Middle Age; Prevalence. .T Community screening for hypercholesterolemia. .P JOURNAL ARTICLE. .W This study focused on a cholesterol screening and education program conducted in Scottsdale, Arizona, to determine the prevalence of hypercholesterolemia among the volunteer participants, and whether such a program motivates lifestyle changes and physician follow-up. The study also examined whether participants used the program to monitor known hypercholesterolemia. During the 6-month program, 1228 individuals were screened. Of these, 29% had a previous history of elevated cholesterol and 5% were on cholesterol-lowering medication. Of the group with no previous history of hypercholesterolemia, 41% had cholesterol levels higher than 5.17 mmol/L (200 mg/dL) and 10% had levels higher than 6.21 mmol/L (240 mg/dL). A subgroup of 120 persons with levels higher than 6.21 mmol/L (240 mg/dL) were contacted 4 to 6 months after the screening. Most of this group reported improvement in diet and exercise patterns, and 58% had consulted a physician. These results suggest that people with known hypercholesterolemia are using community screening programs to monitor their own cholesterol levels, and that such programs identity new high-risk individuals. Program participants appear to change diet and exercise patterns and to seek physician follow-up. .A Bell MM; Joseph S. .I 275784 .U 91011290 .S J Fam Pract 9101; 31(4):369-74 .M Adolescence; Adolescent Psychology/*; Female; Health Education/*MT; Human; Knowledge, Attitudes, Practice/*; Male; Michigan/EP; Smoking/EP/PC/*PX. .T Smoking in adolescence: methods for health education and smoking cessation. A MIRNET study. .P JOURNAL ARTICLE. .W The purpose of this study was to explore smoking behaviors and attitudes among adolescents. A self-administered questionnaire was used to sample adolescents presenting for health care to physicians belonging to MIRNET, a network of family physicians collaborating on research across Michigan. The questionnaire was anonymous and was completed before the visit. Physicians or office nurses were asked to complete a brief face sheet on their patient's demographic information and smoking status, which was linked to the questionnaire through a code number. Twenty-seven percent of female patients and 16% of male patients were smoking and 57% had tried smoking. Knowledge regarding health risks of smoking was high, and the major reasons given for starting to smoke were curiosity and peer behavior. Current smokers reported greater alcohol and marijuana use and cited problems with stress and anxiety, peer behavior, boredom, and the influence of smoking parents and relatives as factors in continuing to smoke. Patients' suggestions for successful smoking cessation focused on peers, explicit messages through pictures, and medication. .A Tuakli N; Smith MA; Heaton C. .I 275785 .U 91011291 .S J Fam Pract 9101; 31(4):376-80 .M Adolescence; Adult; Aged; Auscultation; Blood Pressure; Blood Pressure Determination/IS/*MT/ST; Brachial Artery/PH; Child; Child, Preschool; Comparative Study; Female; Fingers/*BS; Human; Hypertension/DI; Infant; Male; Middle Age; Oscillometry/IS/*MT/ST; Self Care; Sensitivity and Specificity; Support, Non-U.S. Gov't. .T Oscillometric finger blood pressure versus brachial auscultative blood pressure recording. .P CLINICAL TRIAL; JOURNAL ARTICLE. .W In this study, a recently marketed proprietary finger blood pressure monitor, the Marshall, Astro F-88, was compared with the standard auscultative brachial mercury sphygmomanometer on 125 subjects. Measurements were undertaken according to the standards set by the American Heart Association. Sensitivity of the finger blood pressure measurement was 76% for systolic and 75% for diastolic blood pressure in diagnosis of high blood pressure (systolic greater than 140 mm Hg and diastolic greater than 90 mm Hg). Specificity was 86% for systolic and 82% for diastolic blood pressure. Positive predictive values were 58% for systolic and 38% for diastolic blood pressure in the study population in which prevalence of hypertension was 12%. The correlation coefficient (Pearson) for systolic values between devices was 0.76 (P less than .0001) and 0.57 (P less than .0001) for diastolic pressure. Values obtained by the finger monitor were found to be higher than those obtained by the mercury sphygmomanometer. Mean differences and standard deviations (paired t test) for systolic and diastolic pressures between the two devices were 2.3 +/- 14.9 mm Hg (P less than .08) and 2.9 +/- 14.5 mm Hg (P less than .02), respectively. These values are not in accordance with the proposed national standards because only 48% of the systolic and 37% of the diastolic blood pressure measurements were within 5 mm Hg of the mercury sphygmomanometer measurements. Therefore, although these differences may well be due to different techniques of monitoring employed by the devices, this device is not recommended for evaluation of blood pressure. .A Iyriboz Y. .I 275786 .U 91011292 .S J Fam Pract 9101; 31(4):381-6; discussion 386-8 .M Adult; Anxiety/TH; Case Report; Depression/TH; Female; Human; Interprofessional Relations; Physician's Role/*; Physicians, Family; Psychotherapy/*; Stress, Psychological/*/TH. .T Physicians' role in managing emotionally distressed patients already in psychotherapy. .P JOURNAL ARTICLE. .W Much has been written on how physicians should manage patients in emotional distress, including recommendations for making successful referrals to mental health providers. Little has been written, however, on the management of distressed patients who are already in psychotherapy. This article, drawing on three cases, a review of the literature, and systems theory, presents recommendations for managing these patients. Physicians are encouraged to assess these patients for risk of suicide or homicide, substance abuse, and indications for psychotropic medication. They are advised to seek a patient's permission to speak to his or her therapist when the patient may be in immediate danger, when psychotropic medications, hospitalization, or psychiatric consultation is considered, and when the patient fails to respond to ongoing treatment. For patients whose therapists are not psychiatrists, psychiatric consultation is recommended when there are questions about psychotropic medications, when psychiatric and substance abuse disorders coexist, and when hospitalization is considered. Therapists skilled in applying systems theory should be consulted when the patient, psychotherapist, and physician agree that the patient is not making sufficient progress. In most cases, however, physicians should reassure patients about distressing symptoms, avoid expressing opinions about the therapist and psychosocial issues, and encourage patients to renew or to expand their commitment to their psychotherapy. .A Brown RL; Mengel MB. .I 275787 .U 91011293 .S J Fam Pract 9101; 31(4):389-92 .M Aged; Arizona; Diagnosis; Drug Therapy; Family Practice/*ED; Female; Geriatric Assessment/*; Human; Internship and Residency/*SN; Male; Patient Care Team; Physician's Practice Patterns; Support, Non-U.S. Gov't. .T Comprehensive geriatric assessment recommendations: adherence of family practice residents. .P JOURNAL ARTICLE. .W A study was performed to determine whether family practice residents followed recommendations made by a comprehensive geriatric assessment clinic. Of 109 consecutive consultations, 27 patients had follow-up visits with family practice residents who participated in the assessment and who subsequently served as their primary care physicians. Adherence of residents to 437 clinic recommendations was monitored for 90 days by medical record review. Although recommendations to begin or increase a medication were followed 85.4% of the time, residents followed recommendations to stop or decrease medications less than 65% of the time. Recommendations to order a specific laboratory test or x-ray examination were acted on 70.3% of the time. Preventive recommendations were followed only 54.3% of the time. Residents' adherence to team-based care plans varied widely by type of recommendation. Special efforts are needed to increase compliance with comprehensive geriatric assessment clinic recommendations, particularly those for preventive services. .A Reed RL; Kligman EW; Weiss BD. .I 275788 .U 91011294 .S J Fam Pract 9101; 31(4):393-400 .M Adult; Aged; Benzodiazepine Tranquilizers/*; Case Report; Female; Human; Male; Prescriptions, Drug; Substance Abuse/*; Substance Dependence/*. .T Benzodiazepine abuse and dependence: misconceptions and facts [see comments] .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Benzodiazepines can be prescribed for a number of medical conditions. Many physicians are reluctant to prescribe benzodiazepines out of fear of producing dependence in patients and incurring the disapproval of their peers. Studies of psychotropic drug use and abuse demonstrate that individuals using benzodiazepines for treatment of a medical illness rarely demonstrate tolerance to the therapeutic action of the medication or escalate the dose. Eighty percent of benzodiazepines are prescribed for 6 months or less, and elderly women are the most common long-term users of low-dose benzodiazepines. In contrast, recreational use of benzodiazepines is associated with polysubstance abuse, lack of medical supervision, rapid tolerance to the euphoric or sedating side effect, and escalation of dose. Most recreational users of benzodiazepines are young men. Documentation of indication for use, collection of drug-abuse history, close monitoring, and drug holidays can improve the management of this class of medication. .A Farnsworth MG. .I 275789 .U 91011295 .S J Fam Pract 9101; 31(4):401-5 .M Aged; Alzheimer's Disease/DI/RA; Clinical Protocols; Dementia/*DI/RA; Human; Magnetic Resonance Imaging/*/UT; Technology Assessment, Biomedical/*; Tomography, X-Ray Computed/*/UT. .T Should a major imaging procedure (CT or MRI) be required in the workup of dementia? An affirmative view. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .A Katzman R. .I 275790 .U 91011296 .S J Fam Pract 9101; 31(4):405-10 .M Aged; Clinical Protocols; Dementia/DI/*RA; Human; Magnetic Resonance Imaging/UT; Technology Assessment, Biomedical/*; Tomography, X-Ray Computed/*/UT. .T Should a major imaging procedure (CT or MRI) be required in the workup of dementia? An opposing view. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .A Clarfield AM; Larson EB. .I 275791 .U 91011297 .S J Fam Pract 9101; 31(4):411-6 .M Career Choice/*; Human; Internship and Residency/*SN; Kentucky; Physicians, Family; Primary Health Care/*MA; Schools, Medical; Students, Medical/*PX. .T Long-term outcomes of primary care residency choice by graduating medical students in one medical school. .P JOURNAL ARTICLE. .W The ratio of primary care physicians to subspecialists is of major importance to the future of American medicine. This study examined the output of primary care physicians by a state-supported medical school that has a goal of placing 50% of its graduates in primary care. Data were obtained from alumni office questionnaires and published board-certification listings for 1102 graduates of the University of Kentucky College of Medicine from 1973 through 1983. Fifty percent of these graduates chose residency training in primary care. Of all 1102 graduates, 37% are categorized as practicing primary care physicians; 29% of the total are board certified in a primary care discipline. Attrition from primary care as an initial career choice at entry into residency was 26%. With declining medical student interest in primary care and a shortage of primary care physicians, new initiatives in medical education and in the practice of medicine are necessary to balance the specialty distribution of physicians more favorably toward primary care. .A David AK; Blosser A. .I 275792 .U 91011298 .S J Fam Pract 9101; 31(4):417-20 .M Adult; Arachnidism/*/DT/PA; Case Report; Female; Human; Israel; Male; Middle Age. .T Brown spider bites [see comments] .P JOURNAL ARTICLE. .A Sendovski U; Rothman MG; Fried M; Har-Zahav L. .I 275793 .U 91011299 .S J Fam Pract 9101; 31(4):422, 425-6, 429 .M Adolescence; Adult; Child, Preschool; Female; Human; Infant; Male; Mediastinal Emphysema/*/DI/TH. .T Spontaneous pneumomediastinum: evaluation and treatment [see comments] .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .A Holmes KD; McGuirt WF. .I 275794 .U 91011300 .S J Fam Pract 9101; 31(4):431-3, 437-8 .M Adult; Attitude of Health Personnel/*; Forms and Records Control/MT; Human; Medical Records/*; Patients; Physicians, Family/*SN; Primary Prevention; San Francisco; Support, Non-U.S. Gov't. .T Assessment of a patient-held minirecord for adult health maintenance. .P JOURNAL ARTICLE. .A Dickey LL; Petitti D. .I 275795 .U 91011439 .S J Neurol Neurosurg Psychiatry 9101; 53(8):629-32 .M AIDS Dementia Complex/ET; Bacterial Infections/ET; Diagnosis, Differential; Human; Infection/*ET; Nervous System Diseases/*ET; Virus Diseases/ET. .T The widening spectrum of infectious neurological disease [editorial] .P EDITORIAL. .A Kennedy PG. .I 275796 .U 91011440 .S J Neurol Neurosurg Psychiatry 9101; 53(8):633-9 .M Adolescence; Adult; Aged; Aged, 80 and over; Botulinum Toxins/*AD/AE; Child; Child, Preschool; Cranial Nerve Diseases/*TH; Dystonia/*TH; Electromyography/DE; Facial Muscles/IR; Facial Paralysis/*TH; Female; Follow-Up Studies; Human; Infant; Injections, Intramuscular; Male; Middle Age; Prospective Studies; Spasm/*TH; Voice Disorders/*TH. .T Botulinum toxin treatment of cranial-cervical dystonia, spasmodic dysphonia, other focal dystonias and hemifacial spasm. .P JOURNAL ARTICLE. .W In the past five years, 477 patients with various focal dystonias and hemifacial spasm received 3,806 injections of botulinum A toxin for relief of involuntary spasms. A definite improvement with a global rating greater than or equal to 2 on a 0-4 scale, was obtained in all 13 patients with spasmodic dysphonia, 94% of 70 patients with blepharospasm, 92% of 13 patients with hemifacial spasm, 90% of 195 patients with cervical dystonia, 77% of 22 patients with hand dystonia, 73% of 45 patients with oromandibular dystonia, and in 90% of 21 patients with other focal dystonia who had adequate follow up. While the average duration of maximum improvement lasted about 11 weeks after an injection (range seven weeks in patients with hand dystonia to 15 weeks in patients with hemifacial spasm), some patients benefited for over a year. Only 16% of the 941 treatment visits with follow up were not successful. Except for transient focal weakness, there were very few complications or systemic effects attributed to the injections. This study supports the conclusion that botulinum toxin injections are a safe and effective therapy for patients with focal dystonia and hemifacial spasm. .A Jankovic J; Schwartz K; Donovan DT. .I 275797 .U 91011441 .S J Neurol Neurosurg Psychiatry 9101; 53(8):640-3 .M Adult; Aged; Botulinum Toxins/*AD/AE; Double-Blind Method; Electromyography/DE; Female; Human; Injections, Intramuscular; Male; Middle Age; Torticollis/*TH. .T Botulinum toxin treatment in spasmodic torticollis. .P CLINICAL TRIAL; JOURNAL ARTICLE. .W Botulinum toxin A was administered to 19 patients in a double-blind placebo controlled trial. Toxin was more effective than placebo for improving both head position and pain which was measured by an objective rating scale and videofilm assessments. Following the controlled trial, treatment with botulinum toxin was continued in an open fashion. A total of 60 patients with torticollis received toxin in a total of 117 treatment periods. The mean follow up period was 8.4 months. In 39 patients with pain there was benefit in 77% of treatment periods. Some improvement in neck posture occurred in 83% of the treatment periods with a mean duration of 12 weeks. Side effects were frequent with dysphagia being the most common (28% of treatment periods). Botulinum toxin is an effective treatment for toticollis but treatment should be initiated with doses at the lower end of the range used in this study (400-600 mouse units). .A Blackie JD; Lees AJ. .I 275798 .U 91011442 .S J Neurol Neurosurg Psychiatry 9101; 53(8):644-8 .M Adolescence; Adult; Aged; Brain Neoplasms/DI/*GE; Cerebellar Neoplasms/DI/*GE; Female; Follow-Up Studies; Hemangiosarcoma/DI/*GE; Hippel-Lindau Disease/GE; Human; Male; Middle Age; Risk Factors; Spinal Cord Neoplasms/DI/*GE; Support, Non-U.S. Gov't. .T Central nervous system haemangioblastoma: a clinical and genetic study of 52 cases. .P JOURNAL ARTICLE. .W Fifty two cases of haemangioblastoma were reviewed for their clinical, genetic and prognostic features. Of 34 patients with apparently isolated cerebellar lesions, postoperative outcome was good in 79%. Six isolated spinal lesions presented more insidiously and morbidity was related to incomplete resection. Twelve (23%) of the patients definitely had von Hippel-Lindau disease (VHLD). The true proportion may be higher as this diagnosis was not definitely excluded in many of the remainder; only ten patients with seemingly isolated cerebellar tumours were appropriately investigated and two had evidence of VHLD. Four out of 26 cases (15%) with apparently completely resected, isolated, cerebellar lesions later developed recurrent tumours. Brainstem and supratentorial haemangioblastomas were rare and were always associated with VHLD. The cerebellar or spinal haemangioblastomas due to VHLD had no distinctive clinical features compared with isolated tumours and there was considerable overlap in age of onset between the two groups of cases. All patients with an apparently isolated CNS haemangioblastoma should be investigated for evidence of von Hippel-Lindau disease. .A Boughey AM; Fletcher NA; Harding AE. .I 275799 .U 91011443 .S J Neurol Neurosurg Psychiatry 9101; 53(8):649-55 .M Acquired Immunodeficiency Syndrome/DT/*PA; Adult; Biopsy; Case Report; Cellular Inclusions/UL; Cytopathogenic Effect, Viral/PH; Cytoplasm/UL; Human; HIV/*PY; Male; Microscopy, Electron; Middle Age; Muscles/*PA; Muscular Atrophy/CI/*PA; Myofibrils/UL; Necrosis; Sarcoplasmic Reticulum/UL; Support, Non-U.S. Gov't; Zidovudine/AD/*AE. .T Vesicular changes in the myopathies of AIDS. Ultrastructural observations and their relationship to zidovudine treatment. .P JOURNAL ARTICLE. .W Six patients with AIDS and AIDS related complex (ARC) who developed neuromuscular symptoms associated with vesicular changes in muscle fibres are reported. Two patients in the advanced stages of AIDS, who did not receive zidovudine, developed proximal limb weakness and wasting: both had a necrotising myopathy with an unusual segmental vesicular change of myofibres. There were numerous vesicles 0.1 to 2 microns in diameter produced by dilatations of the sarcoplasmic reticulum in fibres depleted of myofibrils. Four patients developed a myopathy while receiving zidovudine for AIDS. One of these had an inflammatory myopathy which showed the development of vesicular change due to enlargement and electron lucency of mitochondria. The three other patients with ARC developed muscle pains or weakness and elevated serum CK while on zidovudine. These patients also showed vesicular changes due to enlargement and electron lucency of mitochondria associated with disruption of sarcomeres and the presence of cytoplasmic bodies. The muscular symptoms resolved when ziduvodine was stopped and repeat biopsy in one case revealed no abnormalities. .A Panegyres PK; Papadimitriou JM; Hollingsworth PN; Armstrong JA; Kakulas BA. .I 275800 .U 91011444 .S J Neurol Neurosurg Psychiatry 9101; 53(8):656-61 .M Adolescence; Adult; Animal; Antibodies, Helminth/*CF; Brain Diseases/*DI/IM; Calcinosis/DI; Cysticercosis/*DI/IM; Cysticercus/*IM; Enzyme-Linked Immunosorbent Assay; Human; Male; Nervous System Diseases/DI; Support, Non-U.S. Gov't; Swine. .T The relationship of antibody levels to the clinical spectrum of human neurocysticercosis. .P JOURNAL ARTICLE. .W One hundred proven cases of cerebral cysticercosis were studied with an enzyme linked immunoassay (ELISA) employing cyst fluid as antigen, with a view to detecting specific antibodies in serum and cerebrospinal fluid (CSF). Antibody levels were correlated with the clinical presentation of the patients, the type and number of cysts detected on their brain scans, the anatomical position of these cysts and the presence of lymphocytes in the CSF. Patients could be divided into two distinct categories, one with low levels of antibody in the serum and absent antibody in the CSF, and the other with high levels in both the serum and the CSF. This differentiation matched the clinical presentation of a benign and a malignant group. Antibody levels could not be related to the type of cysts as observed on the brain scan, but depended on the anatomical position of the cyst, being lower if the cysts were confined to the cerebral cortex. A correlation of antibody levels with the number of cysts was only found in the benign group. .A Zini D; Farrell VJ; Wadee AA. .I 275801 .U 91011446 .S J Neurol Neurosurg Psychiatry 9101; 53(8):667-70 .M Adolescence; Adult; Female; Follow-Up Studies; Heterozygote Detection; Human; Male; Middle Age; Neurologic Examination; Phenotype/*; Reflex, Stretch/*GE; Spinocerebellar Degeneration/*DI/GE; Support, Non-U.S. Gov't. .T Clinical and genetic heterogeneity in early onset cerebellar ataxia with retained tendon reflexes. .P JOURNAL ARTICLE. .W A clinical and genetic study was performed on 20 patients affected by early onset cerebellar ataxia with retained tendon reflexes (EOCA). Mean age at onset was 8.8 (SD 6.0) years. The frequency distribution of age of onset significantly differed from the normal distribution. Consanguinity rate was 16.7% and segregation ratio 0.164. As well as ataxia, which was a constant feature, there were signs of involvement of the cortico-spinal tracts and/or peripheral nerves in most patients. Results of neurophysiological studies were not homogeneous, nor were morphological findings of the sural nerve biopsy. The data suggest that EOCA may be genetically and clinically heterogeneous. .A Filla A; De Michele G; Cavalcanti F; Perretti A; Santoro L; Barbieri F; D'Arienzo G; Campanella G. .I 275802 .U 91011447 .S J Neurol Neurosurg Psychiatry 9101; 53(8):671-4 .M Adult; Anemia, Hypochromic/*BL; Carrier Proteins/BL; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced/BL/DI; Female; Ferritin/BL; Human; Iron/*BL; Male; Middle Age; Psychomotor Agitation/BL/*CI/DI; Risk Factors; Tranquilizing Agents, Major/*AE. .T Low plasma iron status and akathisia. .P JOURNAL ARTICLE. .W Thirty patients were examined to test the hypothesis that a depletion of iron levels is associated with symptoms of akathisia. Fifteen akathisic patients were pair-matched with 15 non-akathisic patients. Plasma ferritin levels were significantly decreased in the akathisic patients, and there was a significant inverse correlation between plasma iron levels and akathisia rating. In addition, akathisia ratings were found to be correlated with a scale measuring symptoms of tardive dyskinesia. .A Barton A; Bowie J; Ebmeier K. .I 275803 .U 91011448 .S J Neurol Neurosurg Psychiatry 9101; 53(8):675-80 .M Adult; Brain/*PA; Case Report; Diagnosis, Differential; Female; Follow-Up Studies; Hemiplegia/*DI; Human; Magnetic Resonance Imaging/*; Male; Middle Age; Multiple Sclerosis/*DI; Neurologic Examination. .T Hemiparetic multiple sclerosis. .P JOURNAL ARTICLE. .W Eight patients are described who presented with hemiparesis which involved the face in seven. Six of the eight subsequently developed clinically definite multiple sclerosis and in the remaining two patients multiple sclerosis was the likely diagnosis. Magnetic resonance imaging gave useful information about the site of the lesions responsible for the presenting syndrome and provided additional information in support of a diagnosis of multiple sclerosis. .A Cowan J; Ormerod IE; Rudge P. .I 275804 .U 91011449 .S J Neurol Neurosurg Psychiatry 9101; 53(8):681-4 .M Adult; Afferent Pathways/PP; Bladder/IR; Bladder, Neurogenic/PP/*TH; Electric Stimulation Therapy/*IS; Electrodes, Implanted/*; Female; Human; Male; Middle Age; Paraplegia/*CO/PP; Postoperative Complications/PP; Spinal Cord Injuries/*CO/PP; Spinal Cord Neoplasms/CO; Spinal Nerve Roots/*PP; Urinary Incontinence/TH. .T Extradural implantation of sacral anterior root stimulators. .P JOURNAL ARTICLE. .W A technique for extradural deafferentation of the S2 to S5 segments and extradural implantation of stimulating electrodes is described, and its application to twelve patients with spinal cord lesions is reported. Nine patients use their implants for micturition, and seven are fully continent. The advantages and disadvantages of this technique compared with the more usual intrathecal procedure are discussed. .A Sauerwein D; Ingunza W; Fischer J; Madersbacher H; Polkey CE; Brindley GS; Colombel P; Teddy P. .I 275805 .U 91011450 .S J Neurol Neurosurg Psychiatry 9101; 53(8):685-90 .M Aged; Attention/*; Cues; Human; Laterality/*; Middle Age; Motor Activity; Neuropsychological Tests/*; Parkinson Disease/DI/*PX; Psychomotor Performance/*. .T Bimanual simultaneous motor performance and impaired ability to shift attention in Parkinson's disease. .P JOURNAL ARTICLE. .W The ability to share time and to shift attention between bimanual simultaneous motor tasks were studied in 18 patients with Parkinson's disease (PD) and 19 age- and intelligence-matched controls. The task consisted of drawing triangles with the dominant hand and squeezing a rubber bulb with the nondominant hand. Motor performance was measured using the variables: amplitude of squeezing, frequency of squeezing and velocity of drawing triangles. After eliminating variance due to baseline differences in single-handed performance, the bimanual simultaneous performance of PD and controls turned out to be similar to the frequency of squeezing and the velocity of drawing triangles. The amplitude of squeezing, however, differed between the two groups: it was significantly reduced in PD. Arguably the disturbance in the bimanual performance of PD patients was not due to a disorder of time sharing, but to a decreased ability to shift attention from the visually cued task to the non visually cued task. The results agree with current evidence that PD patients are more impaired when they have to rely upon internal control for the regulation of shifting attention than when external cues are available. .A Horstink MW; Berger HJ; van Spaendonck KP; van den Bercken JH; Cools AR. .I 275806 .U 91011451 .S J Neurol Neurosurg Psychiatry 9101; 53(8):691-4 .M Adult; Case Report; Compulsive Behavior/SU; Electrocoagulation/MT; Frontal Lobe/SU; Gyrus Cinguli/SU; Human; Limbic System/*SU; Magnetic Resonance Imaging; Male; Postoperative Complications/DI; Psychosurgery/*MT; Self Mutilation/SU; Stereotaxic Techniques; Tourette Syndrome/*SU. .T The treatment of Gilles de la Tourette syndrome by limbic leucotomy. .P JOURNAL ARTICLE. .W A patient with Gilles de la Tourette syndrome and severe self-injurious compulsions who had failed to respond to drug treatment and behavioural therapy obtained a complete and sustained resolution of his destructive behaviour and improvement in his tics following bilateral limbic leucotomy. .A Robertson M; Doran M; Trimble M; Lees AJ. .I 275807 .U 91011452 .S J Neurol Neurosurg Psychiatry 9101; 53(8):695-6 .M Aged; Brain/PA; Carcinoma, Oat Cell/*CO/PA; Case Report; Human; Lung Neoplasms/*CO/PA; Lymph Nodes/PA; Lymphatic Metastasis; Male; Muscle Rigidity/*PA; Paraneoplastic Syndromes/*PA; Spinal Cord/PA; Syndrome. .T Stiffman syndrome: a rare paraneoplastic disorder? .P JOURNAL ARTICLE. .W An unusual case of the stiffman syndrome, associated with an oat cell carcinoma of the bronchus, is reported. Pathological examination showed that it was due to an encephalomyelitis similar to that seen in paraneoplastic disorders. This suggests that atypical cases of the stiffman syndrome may occasionally be paraneoplastic. .A Bateman DE; Weller RO; Kennedy P. .I 275808 .U 91011453 .S J Neurol Neurosurg Psychiatry 9101; 53(8):697-9 .M Brain Neoplasms/DI/*EN/SC; Human; Lactate Dehydrogenase Isoenzymes/*CF; Meningeal Neoplasms/SC; Tumor Markers, Biological/*CF. .T LDH isoenzymes in cerebrospinal fluid in various brain tumours. .P JOURNAL ARTICLE. .W This study examined the isoenzymatic pattern of LDH in the cerebrospinal fluid (CSF) as well as the ratio between the five fractions of LDH among patients with various brain tumours, carcinomatous meningitis and control groups. LDH 1/LDH 2 less than 1 was found significant for carcinomatous meningitis (p less than 0.001) and brain metastases (p less than 0.001). LDH 1/LDH 2 ratio was found to be significantly lower in carcinomatous meningitis than in brain metastases (p less than 0.05). No LDH 1/LDH 2 ratios smaller than 1 were found in the other groups. The LDH 1/LDH 2 ratio smaller than 1 was found in the early stage of carcinomatous meningitis without other evidences of the involvement of the leptomeninges. Examination of LDH 1/LDH 2 can be found as an adjunctive method to identify brain metastases and carcinomatous meningitis at the initial stage. .A Lampl Y; Paniri Y; Eshel Y; Sarova-Pinhas I. .I 275809 .U 91011454 .S J Neurol Neurosurg Psychiatry 9101; 53(8):700-1 .M Aged; Aphasia, Acquired/*DI/PX; Cerebrovascular Disorders/*CO/PX; Female; Home Nursing/*PX; Human; Male; Neuropsychological Tests/*; Nursing Assessment/*; Referral and Consultation/*. .T Misperceptions of comprehension difficulties of stroke patients by doctors, nurses and relatives. .P JOURNAL ARTICLE. .W Doctors, nurses and relatives involved with 30 recently aphasic stroke patients were asked to predict how the patient would perform on a comprehension test. Results show that not only do doctors, nurses and relatives underestimate the receptive disability of these patients, but they also illustrate a lack of agreement between health professionals. Implications for management are considered. .A McClenahan R; Johnston M; Densham Y. .I 275810 .U 91011455 .S J Neurol Neurosurg Psychiatry 9101; 53(8):702-4 .M Attention; Choice Behavior; Human; Neuropsychological Tests; Parkinson Disease/*PX/RH; Practice (Psychology)/*; Psychomotor Performance/*; Reaction Time/*; Support, U.S. Gov't, P.H.S.. .T Practice effects on the preprogramming of discrete movements in Parkinson's disease. .P JOURNAL ARTICLE. .W The effects of practice on the simple and choice reaction times (RTs) of Parkinson's disease (PD) and control subjects in a discrete aiming task were analysed. For controls, practice led to a selective decrease in choice RTs, as has been reported previously. An opposite effect was seen in the PD group, with little change in choice RTs and substantial reduction in simple RTs. The results suggest that PD subjects can use advance information to initiate discrete movements more rapidly, but that this ability to "preprogramme" movements requires practice. Reconciliation of these results with studies reporting an inability to preprogramme in PD are made in a discussion of task characteristics which may allow or preclude preprogramming. .A Worringham CJ; Stelmach GE. .I 275811 .U 91011456 .S J Neurol Neurosurg Psychiatry 9101; 53(8):705-7 .M Electromagnetic Fields/*; Electromyography; Human; Laterality/*PH; Motor Cortex/*PH; Motor Neurons/*PH; Muscle Contraction/*PH; Pyramidal Tracts/*PH; Reaction Time/PH; Support, Non-U.S. Gov't. .T Transcranial magnetic stimulation can influence the selection of motor programmes [published erratum appears in J Neurol Neurosurg Psychiatry 1991 Jun;54(6):510] .P JOURNAL ARTICLE. .W Transcranial magnetic stimulation is becoming increasingly popular to study the rapidly conducting output from the motor cortex. Little is known about the effects of such stimuli on other aspects of cortical function. In the study single magnetic stimuli, subthreshold for movement, produced significant preference for selection of one hand in a forced-choice task. The hand preference depended upon the direction of the induced current. It occurred when the coil was positioned over frontal but not occipital cortex and was not mimicked by weak DC stimulation. Single magnetic stimuli which do not evoke movement can alter high-level motor planning. .A Ammon K; Gandevia SC. .I 275812 .U 91011457 .S J Neurol Neurosurg Psychiatry 9101; 53(8):708 .M Adult; Case Report; Human; Male; Middle Age; Nerve Compression Syndromes/*ET; Neurologic Examination; Occupational Diseases/*ET; Paresthesia/*ET; Peripheral Nerves/*IN; Thigh/*IR; Wounds, Nonpenetrating/ET. .T Occupational meralgia paraesthetica [letter] .P LETTER. .A Garcia-Albea E; Palomo F; Tejeiro J; Cabrera F. .I 275813 .U 91011458 .S J Neurol Neurosurg Psychiatry 9101; 53(8):708-9 .M Adult; Case Report; Chickenpox/*CO; Encephalitis/*CO; Female; Follow-Up Studies; Human; Magnetic Resonance Imaging; Mesencephalon/PA/*PP; Ophthalmoplegia/*PP. .T Vertical gaze palsy due to a resolving midbrain lesion [letter] .P LETTER. .A Trend P; Youl BD; Sanders MD; Kocen RS; McDonald WI. .I 275814 .U 91011459 .S J Neurol Neurosurg Psychiatry 9101; 53(8):709 .M Case Report; Human; Male; Middle Age; Mumps/*CO; Neurologic Examination; Polyradiculoneuritis/*ET. .T Mumps and Guillain-Barre syndrome [letter] .P LETTER. .A Duncan S; Will RG; Catnach J. .I 275815 .U 91011460 .S J Neurol Neurosurg Psychiatry 9101; 53(8):709 .M Adult; Aortic Valve Prolapse/*CO; Cerebral Ischemia, Transient/*ET; Female; Follow-Up Studies; Human; Male; Middle Age; Mitral Valve Prolapse/*CO; Tricuspid Valve Prolapse/*CO. .T The role of combined valve prolapses in the prognosis of cerebro-vascular ischaemic attacks associated with mitral valve prolapse [letter] .P LETTER. .A Matias-Guiu J; Martin R; Insa R; Molto JM; Alvarez J; Codina A; Candell J; Martinez-Vasquez JM. .I 275816 .U 91011462 .S J Neurol Neurosurg Psychiatry 9101; 53(8):710-1 .M Adolescence; Atrophy; Brain/PA; Case Report; Cellular Inclusions/*UL; Human; Locus Coeruleus/*PA; Male; Neurofibrils/UL; Subacute Sclerosing Panencephalitis/*PA; Substantia Nigra/*PA. .T Lewy bodies and subacute sclerosing panencephalitis [letter] .P LETTER. .A Gibb WR; Scaravilli F; Michund J. .I 275817 .U 91011463 .S J Neurol Neurosurg Psychiatry 9101; 53(8):711 .M Adult; Benztropine/AD/*AE; Bipolar Disorder/*DT; Case Report; Coma/*CI; Diagnosis, Differential; Drug Therapy, Combination; Haloperidol/AD/*AE; Human; Lithium/AD; Male; Neuroleptic Malignant Syndrome/*ET. .T Combined neuroleptic malignant syndrome and the central anticholinergic syndrome [letter] .P LETTER. .A Bennett DA. .I 275818 .U 91011464 .S J Neurol Neurosurg Psychiatry 9101; 53(8):711-2 .M Case Report; Cerebral Aneurysm/*SU; Craniotomy; Female; Human; Hypotension, Controlled/MT; Middle Age; Postoperative Complications/ET; Rupture, Spontaneous. .T Intraoperative aneurysms rupture during the predissection stage [letter] .P LETTER. .A Beatty RA. .I 275819 .U 91011465 .S J Neurol Neurosurg Psychiatry 9101; 53(8):713-20 .M Human; Nervous System Diseases/*. .T Proceedings of the Association of British Neurologists. London, 27-29 October 1988. Abstracts. .P MEETING REPORT; OVERALL. .I 275820 .U 91011466 .S J Neurol Neurosurg Psychiatry 9101; 53(8):721 .M Adult; Aged; Baclofen/*AD/AE; Case Report; Dose-Response Relationship, Drug; Human; Injections, Spinal; Male; Paraplegia/*DT; Spastic Paraplegia, Hereditary/*DT. .T Intrathecal baclofen for treatment of spasticity [letter; comment] .P COMMENT; LETTER. .A Vanneste J; Augustijn P. .I 275821 .U 91011475 .S J Clin Epidemiol 9101; 43(10):1021-2 .M Human; Hypercholesterolemia/*TH; Ontario. .T Cholesterol: consensus and controversy [editorial] .P EDITORIAL. .A Linton AL. .I 275822 .U 91011476 .S J Clin Epidemiol 9101; 43(10):1023-7 .M Human; Hypercholesterolemia/*TH; Ontario; Support, U.S. Gov't, P.H.S.. .T Cholesterol policy: what should we do? How should we decide? [editorial] .P EDITORIAL. .A Kottke TE; Brekke ML. .I 275823 .U 91011478 .S J Clin Epidemiol 9101; 43(9):1001-3 .M Diagnosis; Human; Philosophy, Medical/*; Physician-Patient Relations; Professional Practice/*. .T Intimations of uncertainty in the practice of medicine. .P JOURNAL ARTICLE. .A Herman J. .I 275824 .U 91011479 .S J Clin Epidemiol 9101; 43(9):1005-12 .M Coronary Disease/*PP; Exercise; Human; Life Style; Lipids/BL; Oxygen/ME; Physical Fitness/*. .T Fitness and risk factors for coronary disease [letter; comment] .P COMMENT; LETTER. .A Bouchard C; Leon AS; Rao PC; Skinner JS; Wilmore JH. .I 275825 .U 91011480 .S J Clin Epidemiol 9101; 43(9):1012-4 .M Data Interpretation, Statistical/*; Drug Evaluation/*; Human; Product Surveillance, Postmarketing/*ST; United States; United States Food and Drug Administration. .T File drawers, p values and efficacy of drugs [letter; comment] .P COMMENT; LETTER. .A Pagano M; Leviton A. .I 275826 .U 91011481 .S J Clin Epidemiol 9101; 43(9):1014-6 .M Drug and Narcotic Control/*LJ; Drug Evaluation/*; United States; United States Food and Drug Administration. .T Drug banning and the regulatory process [letter; comment] .P COMMENT; LETTER. .A Faich GA. .I 275827 .U 91011482 .S J Clin Epidemiol 9101; 43(9):1016-20 .M Case-Control Studies; Research Design/*ST; Statistics. .T "Would" vs "should" in the definition of secondary study base [letter] .P LETTER. .A Poole C. .I 275828 .U 91011483 .S J Clin Epidemiol 9101; 43(9):849-50 .M Drug Therapy/*AE; Epidemiology/*; Human; Randomized Controlled Trials/*. .T Are drug benefits also part of pharmacoepidemiology? [editorial] .P EDITORIAL. .A Lasagna L. .I 275829 .U 91011484 .S J Clin Epidemiol 9101; 43(9):851-8 .M Confounding Factors (Epidemiology); Diagnosis/*; Female; Hematuria/ET; Human; Lung Neoplasms/ET; Male; Odds Ratio; Probability; Risk Factors/*; Sensitivity and Specificity; Smoking/AE; Urologic Neoplasms/ET. .T The use of risk factors in medical diagnosis: opportunities and cautions. .P JOURNAL ARTICLE. .W We discuss in this paper the extent to which disease risk factors may assist in the diagnostic process. We caution that disease risk factors need not be very sensitive or specific. Risk factor specificity and sensitivity may be further reduced if, in the former case, the risk factor is related to other illnesses having the same clinical presentation as the disease of interest, or if, in the latter case, the risk factor disappears with the onset of illness. We illustrate these points in a discussion of the utility of smoking as a diagnostic test for malignancy in two clinical situations, the patient with asymptomatic microscopic hematuria and the patient with a solitary pulmonary nodule. Risk factors hold great promise as aids to medical diagnosis, as this information is readily available to clinicians at little or no cost. Clinicians, however, should exercise caution when using risk factors of unproven diagnostic utility in medical diagnosis, as their presence may have little or no effect on disease probability. .A Boyko EJ; Alderman BW. .I 275830 .U 91011485 .S J Clin Epidemiol 9101; 43(9):859-66 .M Adult; Blood Pressure/*; Blood Pressure Determination/MT; Cerebrovascular Disorders/EP; Comparative Study; Diastole; Human; Hypertension/CO/DT/*PP; Incidence; Male; Middle Age; Multivariate Analysis; Myocardial Infarction/EP/*PP; Nurses; Physicians; Predictive Value of Tests; Support, U.S. Gov't, P.H.S.. .T Blood pressure reactivity predicts myocardial infarction among treated hypertensive patients. .P JOURNAL ARTICLE. .W High blood pressure (BP) defines a prognostically heterogeneous group. Because BP varies according to time, setting and means of observation, it has been postulated that BP reactivity might better predict cardiovascular disease (CVD) than does unidimensional measurements. To assess BP reactivity, the difference between pretreatment nurse (RN) and physician (MD) diastolic BP (DBP)--systematically recorded in that order--or MD-RN DBP, was obtained in 1737 previously untreated patients with sustained, RN BP greater than or equal to 160 and/or 95 mmHg. Patients stratified by tertiles of MD-RN DBP [(I) less than or equal to - 3, (II) -2 to 3 and (III) greater than or equal to 4 mmHg] were similar by sex, race, age, body mass index, cholesterol, electrocardiography, prior CVD, smoking and pretreatment or attained in-treatment BPs. During 14 years of followup, myocardial infarction (MI) incidence per 1000/year were, tertile I (3.2), II (3.7), III (7.6) (relative risk = 2.4, III vs I + II, p less than 0.05), whereas stroke incidence and non-CVD mortality were evenly distributed. By Cox survival analysis, controlling for other entry characteristics only age, sex and DBP reactivity remained predictive (p less than or equal to 0.03) of MI or total CVD. Thus, BP reactivity, probably a centrally-mediated phenomenon, identifies a subgroup of hypertensives with an increased propensity for MI despite successful BP control. .A Alderman MH; Ooi WL; Madhavan S; Cohen H. .I 275831 .U 91011486 .S J Clin Epidemiol 9101; 43(9):867-73 .M Adult; Denmark/EP; Female; Forced Expiratory Volume; Human; Male; Middle Age; Population Surveillance; Prospective Studies; Respiratory Function Tests/*; Respiratory Tract Diseases/MO/*PP; Risk; Smoking; Support, Non-U.S. Gov't; Urban Population; Vital Capacity. .T Spirometric findings and mortality in never-smokers. .P JOURNAL ARTICLE. .W The relation of ventilatory function to overall mortality has been studied in 662 male and 2048 female never-smokers who during the period 1976-1978 participated in the Copenhagen City Heart Study, a prospective community study of more than 14,000 men and women randomly selected from the general population of the City of Copenhagen. Until the end of 1986, 195 subjects who said they were never-smokers died. Mortality was analyzed using the proportional hazards model of Cox. In addition to measures of ventilatory function, the mortality analysis included age, sex, body-mass index, alcohol consumption, school education, diabetes mellitus, heart disease and bronchial asthma as confounding factors. Forced expiratory volume in 1 second (FEV1) as a percentage of that predicted, forced vital capacity (FVC) as a percentage of that predicted and the ratio of FEV1 to FVC were significant risk factors for mortality among both sexes. The relative risk of death associated with a 50% decrease in FEV1 and FVC as a percentage of a predicted value was 1.65 and 1.81, respectively. This study confirms that lowered ventilatory function is a strong risk factor for mortality among never-smokers of both sexes. .A Lange P; Nyboe J; Appleyard M; Jensen G; Schnohr P. .I 275832 .U 91011487 .S J Clin Epidemiol 9101; 43(9):875-9 .M Coronary Disease/*ET; Human; Hypercholesterolemia/*CO/TH; Hypertension/*CO; Logistic Models; Risk Factors; Smoking/*AE. .T Estimating the benefits of cholesterol lowering: are risk factors for coronary heart disease multiplicative? .P JOURNAL ARTICLE. .W It is often stated that the major risk factors for coronary heart disease (CHD)--smoking, high blood pressure and high serum cholesterol--are not merely additive but act together such that each multiplies the effects of the others. Economic analyses in which the benefits of risk factor modification are estimated often reflect this. This paper explains how predictive models based on the simplest form of the multiple logistic function inevitably predict greater benefit from cholesterol lowering in those in whom other risk factors are adverse; this results from the model itself, rather than the data. CHD death rates from the screenee population of the Multiple Risk Factor Intervention Trial are examined: these suggest that the relationship between cholesterol and both other major risk factors is closer to additive than to multiplicative. When the benefits of cholesterol lowering are estimated, a model based on additive risk, specifying product ("interaction") terms, is to be preferred. .A Silberberg JS. .I 275833 .U 91011488 .S J Clin Epidemiol 9101; 43(9):881-90 .M Arizona/EP; Cohort Studies; Diabetes Mellitus, Non-Insulin-Dependent/CO/*TH; Female; Hospitalization/*SN; Human; Indians, North American/*; Male; Middle Age; Odds Ratio; Patient Admission/SN; Retrospective Studies. .T Hospitalization experience of Navajo subjects with type II diabetes and matched controls: an historical cohort study. .P JOURNAL ARTICLE. .W Using an historical cohort study design with a 12 year follow-up, we found that 77 Navajo adults with type II diabetes mellitus were hospitalized at a rate of 335 hospitalizations per 1000 patient years compared to a rate of 167 hospitalizations per 1000 patient years for 77 age, sex, and residence matched non-diabetic controls, yielding a risk ratio of 2.0. Using matched pairs analysis (sign test), the observed difference in number of hospital admissions is statistically significant (z = 2.30, p less than 0.05). The average duration of hospitalization, however, was not statistically different in matched pairs analysis (z = 0.95, p greater than 0.05). The 136 excess hospitalizations of the diabetic subjects included 45 admissions for poor metabolic control of diabetes, 50 excess admissions for infectious disease, and 26 excess admissions for conditions of the heart, eye, kidney, or non-traumatic amputation. In multivariate analyses, variables found to be associated with greater hospitalization experience among the 77 diabetic subjects in the 12 years follow-up period included older age at entry to the study, poorer metabolic control early in the study period, and presence of diabetic complications. .A O'Connor PJ; Crabtree BF; Nakamura RM; Kelley D. .I 275834 .U 91011489 .S J Clin Epidemiol 9101; 43(9):891-905 .M Epidemiologic Methods/*; Evaluation Studies; Female; Human; Iatrogenic Disease; Information Storage and Retrieval; Male; Meta-Analysis; Preventive Health Services/*; Primary Prevention; Research Design/ST. .T Assessing the clinical effectiveness of preventive maneuvers: analytic principles and systematic methods in reviewing evidence and developing clinical practice recommendations. A report by the Canadian Task Force on the Periodic Health Examination. .P GUIDELINE; JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W This paper examines a process for evaluating clinical effectiveness and developing recommendations in which systematic methods are used to review evidence from published clinical research and to reach sound conclusions about appropriate medical policy. The methodology addresses four important components of the analytic process: (1) the criteria that must be satisfied for a clinical practice to be considered effective; (2) proper methods for reviewing evidence from published clinical research to determine whether a clinical practice meets these criteria (including methods for performing comprehensive literature reviews, for judging the quality of individual studies, and for synthesizing or pooling the results of multiple studies); (3) theoretical and practical concerns in translating the results of the scientific review into sound clinical practice recommendations; and (4) the importance of documentation, guidelines, and other safeguards to minimize the effect the reviewers themselves have on the objectivity and consistency of the analytic methods. .A Woolf SH; Battista RN; Anderson GM; Logan AG; Wang E. .I 275835 .U 91011490 .S J Clin Epidemiol 9101; 43(9):907-11 .M Adult; Alcohol Drinking; Anthropometry; Body Mass Index; Female; Human; Hypertension/*BL; Leukocyte Count/*; Male; Middle Age; Multiphasic Screening; Predictive Value of Tests; Risk; Smoking/AE; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T The leukocyte count: a predictor of hypertension. .P JOURNAL ARTICLE. .W In an exploratory study of 1031 persons observed to progress from normotension to essential hypertension and 1031 matched subjects who remained normotensive, the initial leukocyte count (WBC) was found to be related to the development of hypertension, with risk increased 40% (95% confidence interval 12-82%) in persons in the highest as compared to the lowest quartile of WBC. This relationship proved to be largely independent of body mass index, body fat distribution, alcohol and tobacco consumption, and parental history of hypertension. An increased WBC may reflect greater sympathetic tone or may directly increase peripheral vascular resistance by impeding circulation through small blood vessels. If confirmed, this study adds another condition to the growing list for which the WBC is predictive. This simple, cheap test should be considered for inclusion in prospective epidemiological studies of many different diseases. .A Friedman GD; Selby JV; Quesenberry CP Jr. .I 275836 .U 91011491 .S J Clin Epidemiol 9101; 43(9):913-9 .M Adult; Age Factors; Alcohol Drinking; Coronary Disease/*BL/ET; Female; Fibrinogen/*AN; Human; Life Style; Male; Middle Age; Risk Factors; Sex Factors; Smoking/AE; Social Class; Support, Non-U.S. Gov't. .T Plasma fibrinogen and coronary risk factors: the Scottish Heart Health Study. .P JOURNAL ARTICLE. .W Plasma fibrinogen was measured in a sample of 8824 men and women aged 40-59 years participating in the Scottish Heart Health Study, and related to cardiovascular risk factors. Women had higher fibrinogen levels than men. In both sexes, multivariate analysis showed that fibrinogen was positively associated with age, smoking, total cholesterol and body mass index and negatively associated with alcohol consumption. Among women, early menopause and systolic blood pressure were also associated with fibrinogen levels. Univariate analyses showed weak positive associations with fish consumption for both sexes although only male white fish consumption entered the final model. Women with a history of contraceptive pill usage had significantly lower fibrinogen levels. The relationship between fibrinogen and physical activity was complex, and could largely be explained by smoking. These findings support the hypothesis that raised fibrinogen is one mechanism by which several major risk factors may promote coronary heart disease. However, known risk factors explained, at most, 10% of the total variance in fibrinogen levels among the general population. .A Lee AJ; Smith WC; Lowe GD; Tunstall-Pedoe H. .I 275837 .U 91011492 .S J Clin Epidemiol 9101; 43(9):921-40 .M Adult; Aged; Anthropometry; Apolipoproteins/BL/*GE; Child; Cholesterol/BL; Coronary Disease/*BL; Female; Human; Lipids/BL/*GE; Male; Phenotype; Sampling Studies; Sex Factors; Support, U.S. Gov't, P.H.S.; Triglycerides/BL. .T The effects of generation and gender on the joint distributions of lipid and apolipoprotein phenotypes in the population at large. .P JOURNAL ARTICLE. .W The generation and gender effects on the joint distributions of total plasma cholesterol (Total-C), ln triglycerides (lnTrig), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), apolipoproteins AI (Apo AI), AII (Apo AII), and E (lnApo E) were studied in 184 male grandparents (MGP), 242 female grandparents (FGP), 237 male parents (MP), 235 female parents (FP), 202 male children (MC), and 200 female children (FC). Homogeneity of variance tests revealed that lipid variances were gender and/or generation specific while apolipoprotein variances were homogeneous across strata. In the absence of heterogeneity of variance, significant heterogeneity in LDL:lnTrig and lnTrig:Apo AII covariation was found between genders in the parental generation. In the presence of heterogeneity of variance, significant heterogeneity of correlation between genders and/or across generations was found for the HDL-C:LDL-C, Total-C:LDL-C, Total-C:lnTrig, lnTrig:LDL-C, Total-C:lnApo E and HDL-C:lnApo E bivariate distributions. Analyses of principal components revealed that the generation and gender specific cohorts have similar eigenvalues but distinct eigenvectors for the first two principal components underlying the seven dimensional lipid and apolipoprotein distribution. We conclude that the amount of variability explained by the first two principal components is the same across cohorts but how the interindividual variability is distributed among the lipid and apolipoprotein traits is generation and gender specific. This study documents the role that variance and covariance might play in determining risk of disease for special subgroups of the population at large. It also demonstrates how variances and covariances between risk factors traits characterize life processes of aging and sexual dimorphism. This study argues that future biometrical genetic and epidemiological studies of coronary artery disease must take into account age and gender effects on interindividual variability and covariability of risk factors. .A Reilly SL; Kottke BA; Sing CF. .I 275838 .U 91011493 .S J Clin Epidemiol 9101; 43(9):941-7 .M Environmental Exposure/*; Epidemiologic Methods/*; Human; Odds Ratio; Predictive Value of Tests; Risk; Sampling Studies. .T Validation study methods for estimating exposure proportions and odds ratios with misclassified data. .P JOURNAL ARTICLE. .W Two methods for making adjustments to an estimate of exposure when data are possibly misclassified are discussed. One, the indirect method, is widely used but the other, the direct method, seems less well-known, despite it being a rather more obvious approach. To implement either requires some knowledge of misclassification rates and it may be possible to estimate these by a validation study. Depending on how sampling for such a study is done, one has the choice of what method to use. Formulae for the variance of estimates are derived and the precision of the methods compared. The direct approach is found to be more efficient. .A Marshall RJ. .I 275839 .U 91011494 .S J Clin Epidemiol 9101; 43(9):949-60 .M Adult; Aged; Alcohol Drinking; Anthropometry; Blacks/*; Body Mass Index/*; Cohort Studies; Educational Status; Female; Human; Male; Middle Age; Mortality/*; Obesity/CO; Regression Analysis; Smoking; Support, U.S. Gov't, P.H.S.; United States. .T Body mass index and 15-year mortality in a cohort of black men and women. .P JOURNAL ARTICLE. .W The association between body mass index (BMI) and mortality was investigated in 2453 black male (aged 30-79 years) and 2731 black female (aged 40-79 years) members of the Kaiser Foundation Health Plan. During a 15-year follow-up 393 male and 283 female deaths were identified. Analyses were conducted separately in a lower and an upper range of BMI (as well as over the entire range), to isolate separate effects of low weight and high weight on mortality. Particular attention was also paid to potential bias from cigarette smoking and antecedent illness. Cox regression analyses showed that over the entire range of BMI the adjusted BMI-mortality association was significantly J-shaped for the men and essentially flat for the women. The inverse association between BMI and mortality in the lower range of BMI was statistically significant for the men; the adjusted relative hazard increasing from the 10th to the 50th percentile of BMI was 0.76 (95% confidence interval [CI] 0.59-0.98). The positive association between BMI and mortality in the upper range of BMI was highly statistically significant for the men; the adjusted relative hazard increasing from the 50th to the 90th percentile of BMI was 1.37 (95% CI 1.14-1.63). Whether controlled by multivariate analysis, by excluding the first 5 years of follow-up from the analyses, or by analyzing the BMI-mortality association in smoking-specific and/or illness-specific subgroups, smoking and antecedent illness did not have much impact on the BMI-mortality association, in either sex. The general observations on the BMI-mortality association are similar to findings in some white cohorts. .A Wienpahl J; Ragland DR; Sidney S. .I 275840 .U 91011495 .S J Clin Epidemiol 9101; 43(9):961-70 .M Adult; Aged; Cardiovascular Diseases/*EP/ET; Data Interpretation, Statistical; Human; Middle Age; Models, Statistical/*; Odds Ratio; Risk Factors; Support, U.S. Gov't, P.H.S.. .T Risk ratios and risk differences in estimating the effect of risk factors for cardiovascular disease in the elderly. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W This article reviews the nature of the effects of hypertension, smoking and cholesterol on the incidence of cardiovascular disease and emphasizes how these effects vary by age. In the Methods section, we discuss briefly the concepts of additive and multiplicative statistical models as tools for summarizing data. In the results section, we summarize available data on the association between incident stroke and coronary heart disease in the elderly and each of these major risk factors. The traditional multiplicative model parsimoniously characterizes the individual and joint effects of age and high blood pressure in terms of risk ratios; but, for smoking and cholesterol, an additive model appears to be the most parsimonious. We discuss the consequences of these observations for the study and prevention of cardiovascular disease in the elderly. .A Psaty BM; Koepsell TD; Manolio TA; Longstreth WT Jr; Wagner EH; Wahl PW; Kronmal RA. .I 275841 .U 91011497 .S J Clin Epidemiol 9101; 43(9):977-82 .M Adolescence; Adult; Age Factors; Aged; Carcinoma in Situ/*SU; Cervix Neoplasms/*SU; Comparative Study; Female; Human; Hysterectomy/*; Middle Age; New Mexico; Support, U.S. Gov't, P.H.S.; Surgery, Operative/MT. .T Changes in surgical treatments: the example of hysterectomy versus conization for cervical carcinoma in situ. .P JOURNAL ARTICLE. .W From 1969 through 1985, 4584 women in the state of New Mexico were diagnosed with carcinoma in situ of the cervix. Of these women, 65.5% underwent hysterectomy while 31.1% had a conservative therapy (primarily conization). Over the 17-year period, there was a steady increase in the percentage of women receiving conservative therapies, from 11.8% in 1969 to 50.3% in 1985. Younger women, unmarried women and American Indian women were more likely to receive conservative therapy. This marked shift in therapeutic approach occurred during a time of apparent controversy as to the optimal treatment for cervical carcinoma in situ, and illustrates a rapid change in surgical practice in the absence of any controlled trials comparing the two major treatment modalities. .A Goodwin JS; Hunt WC; Key CR; Samet JM. .I 275842 .U 91011498 .S J Clin Epidemiol 9101; 43(9):983-94 .M Adolescence; Adult; Cluster Analysis; Female; Headache/*CL/CO/EP; Human; Male; Migraine/CL; Nausea/CO; Odds Ratio; Regression Analysis; Severity of Illness Index; Stress/CO; Support, U.S. Gov't, P.H.S.; Time Factors; Vomiting/CO. .T The relationship of headache symptoms with severity and duration of attacks. .P JOURNAL ARTICLE. .W Efforts to develop clinically useful headache classification schemes have generally focused on linking specific symptom groupings with specific headache subtypes. An alternative conceptual approach, the "severity model" of headache, considers a continuum of headache ranging from mild to severe forms with specific headache subtypes distinguished by level of severity rather than unique constellations of symptoms. A population-based telephone interview was carried out among 10,169 subjects aged 12-29 to estimate the prevalence of serious headaches and better characterize symptoms that accompany headache attacks. In an analysis of frequency of occurrence, pain and duration of recent (within 4 weeks prior to interview) headache attacks, the data revealed that common symptoms (such as forehead pain and pain in the back of the head, neck and shoulders) were reported frequently, but headaches with these symptoms were generally characterized by low levels of pain and short duration. Although not an original study objective, the data were analyzed to determine whether distinct symptom constellations could be identified or whether symptoms overlapped between headache types. Symptoms of migraine were frequently experienced concomitant with tension-type symptoms; the resultant headaches were usually characterized as moderate in intensity. In contrast, symptoms usually associated with migraine in the absence of concomitant tension-type symptoms were infrequently experienced, but resulted in headaches causing the greatest disability. The data provide some support for the severity model of headache. .A Celentano DD; Stewart WF; Linet MS. .I 275843 .U 91011499 .S J Clin Epidemiol 9101; 43(9):995-1000 .M Adolescence; Adult; Aged; Anxiety Disorders/*DI/PX; Female; Human; Male; Middle Age; Psychological Tests/*; Psychometrics/*; Regression Analysis. .T Shortening the State-Trait Anxiety Inventory. .P JOURNAL ARTICLE. .W Questionnaires that are used in studies with severely patients should be as short as possible. Abridged versions of existing inventories are very practical in these instances. The answers of 444 subjects in three samples (cancer patients, medical students, surgical patients) were used to investigate the possibility of constructing short and reliable versions of the scales of the State and Trait Anxiety Inventory. A stepwise regression procedure showed the possibility to reliably predict the total score of the unabridged versions by means of weighted sums of eight items for each scale. Omission of weights did not lead to substantial loss of information. Cronbach's alpha of the State-scale decreased from 0.93 to about 0.85 for different combinations of items and from 0.91 to about 0.82 for combinations of eight items of the Trait-scale. The relationship between both scales was only slightly modified by the shortening procedure. .A van Knippenberg FC; Duivenvoorden HJ; Bonke B; Passchier J. .I 275844 .U 91011510 .S J Clin Oncol 9101; 8(10):1607-9 .M Administration, Oral; Carcinoma, Oat Cell/DT; Drug Administration Schedule; Etoposide/*AD/AE/PK; Human; Lung Neoplasms/DT; Remission Induction. .T Low-dose oral etoposide: a new role for an old drug? [editorial] .P EDITORIAL. .A Slevin ML. .I 275845 .U 91011511 .S J Clin Oncol 9101; 8(10):1610-2 .M Human; Immunization, Passive/*; Infusions, Parenteral; Interleukin-2/AD; Killer Cells, Lymphokine-Activated/TR; Peritoneal Neoplasms/*TH. .T Intraperitoneal adoptive immunotherapy for peritoneal cancer. [editorial] .P EDITORIAL. .A Berek JS. .I 275846 .U 91011512 .S J Clin Oncol 9101; 8(10):1613-7 .M Administration, Oral; Aged; Aged, 80 and over; Carcinoma, Oat Cell/*DT/MO; Drug Administration Schedule; Drug Evaluation; Etoposide/*AD/AE/TU; Female; Human; Leukopenia/CI; Lung Neoplasms/*DT/MO; Male; Middle Age; Neoplasm Recurrence, Local/*DT/MO; Remission Induction; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Survival Rate; Thrombocytopenia/CI. .T Prolonged administration of oral etoposide in patients with relapsed or refractory small-cell lung cancer: a phase II trial. .P JOURNAL ARTICLE. .W Twenty-two patients with recurrent small-cell lung cancer (SCLC) were treated with single-agent etoposide 50 mg/m2/d by mouth for 21 consecutive days. Eleven patients had received previous chemotherapy with cyclophosphamide, doxorubicin, and vincristine (CAV) or etoposide (CAE) or both (CAVE). Four of the latter patients also received salvage treatment with cisplatin and etoposide (EP). Nine patients had been treated with EP as induction therapy, while two patients had received high-dose cyclophosphamide, etoposide and cisplatin (HDCEP). Altogether, 18 patients had received previous intravenous etoposide. The median time off chemotherapy was 4.5 months (range, 1 to 28.9 months). Ten patients (45.5%; 95% confidence interval [CI], 27% to 65%) achieved a complete or partial response. Responses were most common in patients who had responded to previous chemotherapy and who had not received any treatment in the 90 days before initiation of oral etoposide. Median response duration was 4 months (range, 1.5 to 9.5 months) and median survival was 3.5+ months (range, 1.0 to 15+ months). Leukocyte and platelet nadirs were 1,800/microL and 160,000/microL, respectively, during cycle 1 of treatment and occurred between days 21 and 28. Overall, total leukocyte count decreased to less than 1,000/microL during 10 of 56 cycles (18%). Five patients required six hospitalizations for neutropenia and fever. There were two toxic deaths due to sepsis. Platelet counts less than 50,000/microL occurred in 14 cycles (25%). Alopecia developed in all patients; gastrointestinal toxicity was uncommon. This schedule of etoposide administration warrants further study in combination with other active agents in previously untreated patients with SCLC. .A Johnson DH; Greco FA; Strupp J; Hande KR; Hainsworth JD. .I 275847 .U 91011513 .S J Clin Oncol 9101; 8(10):1618-29 .M Adult; Aged; Colorectal Neoplasms/TH; Evaluation Studies; Female; Fibrosis; Human; Immunotherapy, Adoptive/*; Infusions, Parenteral; Interleukin-2/*AD/AE/TU; Killer Cells, Lymphokine-Activated/*TR; Male; Middle Age; Ovarian Neoplasms/TH; Peritoneal Cavity/PA; Peritoneal Neoplasms/*TH; Recombinant Proteins/AD/AE/TU; Remission Induction; Support, U.S. Gov't, P.H.S.; Uterine Neoplasms/TH. .T Intraperitoneal lymphokine-activated killer-cell and interleukin-2 therapy for malignancies limited to the peritoneal cavity. .P JOURNAL ARTICLE. .W Autologous lymphokine-activated killer (LAK) cells and recombinant human interleukin-2 (rIL-2) were administered intraperitoneally (IP) to 24 patients with malignancies limited to the peritoneal space. Ten patients had ovarian cancer, 12 had colorectal cancer, and one patient each had endometrial carcinoma and primary small-bowel adenocarcinoma. All ovarian cancer patients, three of twelve colorectal cancer patients, and one patient with endometrial carcinoma had received prior therapy. Patients received IL-2 100,000 U/kg every 8 hours intravenously (IV) for 3 days, and 2 days later underwent daily leukapheresis for 5 days. LAK cells were generated in vitro by incubating the peripheral blood mononuclear cells in IL-2 for 7 days and were then administered IP daily for 5 days through a Tenckhoff catheter (Davol, Inc, Cranston, RI) together with IL-2 25,000 U/kg IP every 8 hours. All but one patient completed at least one cycle of therapy. Toxic side effects included minor to moderate hypotension, fever, chills, rash, nausea, vomiting, abdominal pain and distension, diarrhea, oliguria, fluid retention, thrombocytopenia, and minor elevations of liver function tests; all of these rapidly improved after discontinuation of IL-2. One patient had a grand mal seizure, and one suffered a colonic perforation; these were felt to be treatment-related. IP fibrosis developed in 14 patients and limited repeated cyclic administration of this therapy in five patients. Two of 10 (20%) ovarian cancer patients and five of 12 (42%) colorectal cancer patients had laparoscopy- or laparotomy-documented partial responses. We conclude that LAK cells and rIL-2 can be administered IP to cancer patients, resulting in moderate to severe short-term toxicity and modest therapeutic efficacy. Further investigation of this form of adoptive immunotherapy modified to address the problem of IP fibrosis and with lower IP IL-2 doses is justified by these initial results. .A Steis RG; Urba WJ; VanderMolen LA; Bookman MA; Smith JW 2d; Clark JW; Miller RL; Crum ED; Beckner SK; McKnight JE; et al. .I 275848 .U 91011514 .S J Clin Oncol 9101; 8(10):1630-6 .M Adult; Anuria/ET; Carcinoma, Renal Cell/*TH; Drug Administration Schedule; Drug Evaluation; Female; Human; Hypotension/ET; Immunotherapy, Adoptive/*; Infusions, Intravenous/MT; Interleukin-2/*AD/AE/TU; Kidney Neoplasms/*TH; Killer Cells, Lymphokine-Activated/*TR; Male; Middle Age; Remission Induction; Support, U.S. Gov't, P.H.S.. .T Therapy of renal cell carcinoma with interleukin-2 and lymphokine-activated killer cells: phase II experience with a hybrid bolus and continuous infusion interleukin-2 regimen. .P CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY. .W Forty-seven patients with metastatic or unresectable renal cell carcinoma were treated with interleukin-2 (IL-2) and lymphokine-activated killer (LAK)-cell therapy, using a hybrid IL-2 regimen. IL-2 was administered initially by intravenous bolus (10(5) U/kg [Cetus Corp, Emeryville, CA] every 8 hours for 3 days) during the priming phase, and subsequently by continuous infusion (3 x 10(6) U/m2 for 6 days); during this second treatment period, in vitro-generated LAK cells were administered. Despite selection of patients for good performance status (PS) (29, PS 0; 18, PS 1) prior nephrectomy (43 of the 47 patients), and low tumor burden, the response rate was low (two complete [CRs] and two partial responses [PRs], for an overall objective response rate of 9%). Toxicity was comparable to that experienced with the high-dose bolus regimen. These results suggest that the dose and schedule of IL-2 administration may influence the likelihood of response to IL-2 in renal cell carcinoma. .A Parkinson DR; Fisher RI; Rayner AA; Paietta E; Margolin KA; Weiss GR; Mier JW; Sznol M; Gaynor ER; Bar MH; et al. .I 275849 .U 91011516 .S J Clin Oncol 9101; 8(10):1650-6 .M Adult; Aged; Drug Administration Schedule; Drug Evaluation; Female; Human; Hypotension/ET; Interleukin-2/AD/AE/*TU; Liver Neoplasms/SC/TH; Lung Neoplasms/SC/TH; Male; Melanoma/SC/*TH; Middle Age; Neoplasm Metastasis; Recombinant Proteins/AD/AE/TU; Remission Induction; Support, U.S. Gov't, P.H.S.; United States. .T Interleukin-2 therapy in patients with metastatic malignant melanoma: a phase II study. .P CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY. .W Forty-seven patients with metastatic malignant melanoma were treated with two 5-day cycles of 100,000 U/kg recombinant interleukin-2 (IL-2) intravenously (IV) every 4 hours separated by 1 week. This dose and schedule of IL-2 were identical to those used in a previous combined IL-2 and lymphokine-activated killer (LAK) cell phase II clinical trial of the IL-2/LAK Working Group. Patient eligibility criteria, and clinical management guidelines were similar to those used in the previous trial. Forty-six patients were assessable for response. Objective responses were observed in 10 of 46 patients (two complete responses [CRs], eight partial responses [PRs]) or 22% with responses occurring in lung and liver as well as lymph nodes and subcutaneous sites. The median response duration was 8 months. Toxicity was significant; three patients developed myocardial infarction, and one patient died during therapy. Overall the toxicity and response rate for single-agent IL-2 are similar to that observed with IL-2 administered in combination with LAK cells in the previous trial. These results suggest that single-agent therapy with IL-2 when administered in this schedule has significant antimelanoma activity in humans, and that LAK cells generated from peripheral blood add little to the antimelanoma activity of this dose and schedule of IL-2. .A Parkinson DR; Abrams JS; Wiernik PH; Rayner AA; Margolin KA; Van Echo DA; Sznol M; Dutcher JP; Aronson FR; Doroshow JH; et al. .I 275850 .U 91011517 .S J Clin Oncol 9101; 8(10):1657-63 .M Adult; Aged; Ambulatory Care; Carcinoma, Renal Cell/TH; Drug Administration Schedule; Drug Evaluation; Fatigue/ET; Female; Human; Infusions, Intravenous; Injections, Intramuscular; Interferon Alfa-2a/*AD/AE/TU; Interleukin-2/*AD/AE/TU; Kidney Neoplasms/TH; Male; Middle Age; Neoplasms/*TH; Recombinant Proteins/AD/AE/TU; Remission Induction. .T Phase I study of interleukin-2 and interferon alfa-2a as outpatient therapy for patients with advanced malignancy. .P JOURNAL ARTICLE. .W Twenty-six patients were treated in this phase I study with the combination of interleukin-2 (IL2) administered as a continuous infusion and interferon alfa-2a (IFN alpha-2a) administered intramuscularly to patients in an outpatient setting. The maximum-tolerated dose of both agents given as outpatient therapy was 2 x 10(6) U/m2 days 1 to 5 of IL2 and 9 x 10(6) U/m2 days 1, 3, and 5 of IFN alpha-2a for 4 consecutive weeks. A 2- to 4-week rest period was permitted after each 4 weeks of treatment. Fatigue was the treatment-limiting toxicity, and serious clinical or laboratory abnormalities occurred infrequently during this study. Patients with colon cancer metastatic to the liver tolerated treatment worse than patients with other tumors. Twelve of the 15 patients with renal cell cancer were assessable for response determinations. Of these 12 patients, three exhibited complete tumor regression, three have had partial objective regression, and three patients experienced stabilization of rapidly progressive disease. This therapy appears to be well tolerated in an outpatient treatment setting and shows significant activity against advanced renal cell cancer. .A Hirsh M; Lipton A; Harvey H; Givant E; Hopper K; Jones G; Zeffren J; Levitt D. .I 275851 .U 91011518 .S J Clin Oncol 9101; 8(10):1664-74 .M Adolescence; Adult; Age Factors; Antineoplastic Agents, Combined/TU; Bone Neoplasms/MO/PA/*TH; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide/AD; Dactinomycin/AD; Doxorubicin/AD; Female; Follow-Up Studies; Human; Male; Neoplasm Metastasis; Neoplasm Recurrence, Local; Prognosis; Sarcoma, Ewing's/MO/PA/*TH; Support, U.S. Gov't, P.H.S.; Survival Rate; United States; Vincristine/AD. .T Multimodal therapy for the management of primary, nonmetastatic Ewing's sarcoma of bone: a long-term follow-up of the First Intergroup study. .P CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL. .W A total of 342 previously untreated eligible children were entered into the first Intergroup Ewing's Sarcoma Study (IESS) between May 1973 and November 1978. In group I institutions, patients were randomized between treatment 1 (radiotherapy to primary lesion plus cyclophosphamide, vincristine, dactinomycin, and Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH] [VAC plus ADR]) or treatment 2 (same as treatment 1 without ADR), and group II institutions randomized patients between treatment 2 or treatment 3 (same as treatment 2 plus bilateral pulmonary radiotherapy [VAC plus BPR]). The percentages of patients relapse-free and surviving (RFS) at 5 years for treatments 1, 2, and 3 were 60%, 24%, and 44%, respectively. There was strong statistical evidence of a significant advantage in RFS for treatment 1 (VAC plus ADR) versus 2 (VAC alone) (P less than .001) and 3 (P less than .05) and also of treatment 3 versus 2 (P less than .001). Similar significant results were observed with respect to overall survival. Patients with disease at pelvic sites have significantly poorer survival at 5 years than those with disease at nonpelvic sites (34% v 57%; P less than .001). Among pelvic cases, there was no evidence of differing survival by treatment (P = .81), but among nonpelvic cases, there was strong evidence of differing survival by treatment (P less than .001). The overall percentage of patients developing metastatic disease was 44%; the percentages by treatments 1, 2, and 3 were 30%, 72%, and 42%, respectively. The overall incidence of local recurrence was 15%, and there was no evidence that local recurrence rate differed by treatment. Patient characteristics related to prognosis, both with respect to RFS and overall survival experience, were primary site (nonpelvic patients were most favorable) and patient age (younger patients were more favorable). .A Nesbit ME Jr; Gehan EA; Burgert EO Jr; Vietti TJ; Cangir A; Tefft M; Evans R; Thomas P; Askin FB; Kissane JM; et al. .I 275852 .U 91011519 .S J Clin Oncol 9101; 8(10):1675-82 .M Adult; Aged; Antineoplastic Agents, Combined/*AD/TU; Combined Modality Therapy; Comparative Study; Cyclophosphamide/AD; Diethylstilbestrol/AD/TU; Doxorubicin/AD; Human; Linear Models; Male; Middle Age; Orchiectomy; Proportional Hazards Models; Prostatic Neoplasms/DT/SU/*TH; Remission Induction; Support, U.S. Gov't, P.H.S.; United States. .T Combined versus sequential chemo-endocrine therapy in advanced prostate cancer: final results of a randomized Southwest Oncology Group study. .P CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL. .W Cytotoxic chemotherapy has not provided survival benefit in metastatic prostate cancer, although it has been used most frequently in patients with far-advanced, refractory disease. To evaluate the effects of chemotherapy given earlier in the course of the disease, the Southwest Oncology Group (SWOG) performed a randomized trial between September 1982 and October 1986 comparing endocrine therapy (diethylstilbestrol [DES] or orchiectomy) alone followed by cyclophosphamide-Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) chemotherapy at progression versus initial combined chemo-endocrine therapy. One hundred forty-three patients were registered, and only six were declared ineligible. Patients on the combined chemo-endocrine therapy arm had a slightly higher response rate (63%) compared with endocrine therapy alone (48%). A log-linear model of tumor response and treatment arm adjusted for the stratification factors favored the combination arm (P = .059). Only three of 27 patients on the endocrine therapy alone arm had an objective partial response when crossed over to chemotherapy, while two others had stable disease. Despite the difference in initial response rate, time to treatment failure and survival were identical in the two treatment arms. Seventy-seven percent of patients on the initial endocrine therapy alone arm have died (median survival, 25.6 months) compared with 78% on the chemo-endocrine therapy arm (median survival, 22.0 months). No significant effect of treatment on survival was observed even after adjustment for the stratification variables in a Cox regression model. Exploratory survival analyses with patients on both arms combined did show a marginally significant time to treatment failure and survival advantage for patients treated with DES rather than orchiectomy as initial endocrine therapy. Eighty-six percent of patients treated by orchiectomy have died compared with only 65% of those treated with DES. These data do not support the addition of cytotoxic chemotherapy to initial endocrine therapy in patients with metastatic prostate cancer. .A Osborne CK; Blumenstein B; Crawford ED; Coltman CA Jr; Smith AY; Lambuth BW; Chapman RA. .I 275853 .U 91011520 .S J Clin Oncol 9101; 8(10):1683-94 .M Antineoplastic Agents, Combined/TU; Combined Modality Therapy; Human; Lung Neoplasms/DT/PA/SU; Lymph Node Excision; Mediastinal Neoplasms/DT/PA/SU; Multivariate Analysis; Neoplasms, Embryonal and Mixed/DT/PA/*SU; Prognosis; Regression Analysis; Retroperitoneal Neoplasms/DT/PA/SU; Retroperitoneal Space; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tumor Markers, Biological/BL. .T Adjunctive surgery after chemotherapy for nonseminomatous germ cell tumors: recommendations for patient selection. .P JOURNAL ARTICLE. .W One hundred eighty-five patients who underwent surgery within 6 months of completing chemotherapy were identified from 360 patients with nonseminomatous germ cell tumors (NSGCT) treated with Memorial Hospital front-line cisplatin- or carboplatin-based combination chemotherapy protocols between 1979 and 1988. Clinical, pathologic, and radiologic features were correlated with the pathologic findings at surgery. The size of a residual retroperitoneal mass, the degree of shrinkage that occurred with chemotherapy, and the presence of teratomatous elements in pretreatment pathology specimens were each correlated with the pathologic findings of retroperitoneal resections after chemotherapy. Multivariable logistic regression analysis of those undergoing retroperitoneal resections identified the size and shrinkage of the residual mass and the prechemotherapy lactate dehydrogenase (LDH) and alphafetoprotein (AFP) levels as the best predictors of finding only necrotic debris. No factors could be found, however, that could selectively exclude patients who had residual viable malignancy or teratoma in the retroperitoneum. Of 39 patients with residual retroperitoneal masses measuring less than or equal to 1.5 cm in maximal diameter, three had residual malignancy and five had teratoma resected. No factors were identified for residual lung or mediastinal masses that could be used to select a group of patients who could safely avoid surgery. If serum markers have normalized after chemotherapy for NSGCT, resection of all residual abnormalities on imaging studies of the retroperitoneum, lungs, and mediastinum is recommended. In addition, retroperitoneal lymph node dissection (RPLND) is recommended for all patients with initial bulky metastases (greater than or equal to 3 cm in diameter) in the retroperitoneum, irrespective of the findings of postchemotherapy computed tomography (CT). .A Toner GC; Panicek DM; Heelan RT; Geller NL; Lin SY; Bajorin D; Motzer RJ; Scher HI; Herr HW; Morse MJ; et al. .I 275854 .U 91011522 .S J Clin Oncol 9101; 8(10):1699-706 .M Adult; Bone Marrow Transplantation/*AE; Carmustine/AD/AE; Combined Modality Therapy; Female; Hepatic Veno-Occlusive Disease/*ET; Human; Liver Neoplasms/SC; Lymphoma/DT/*SU; Male; Middle Age; Neoplasms/DT/*SU; Prognosis; Retrospective Studies; Risk Factors; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Hepatic venoocclusive disease in autologous bone marrow transplantation of solid tumors and lymphomas. .P JOURNAL ARTICLE. .W Retrospective review of 291 solid tumor and lymphoma patients undergoing autologous bone marrow transplantation (BMT) was performed to determine the influence of pretransplant characteristics and preparative regimen to the development of hepatic venoocclusive disease (VOD). Twelve patients (4.1%) developed a clinical syndrome of right upper quadrant (RUQ) tenderness or hepatomegaly, jaundice, and ascites, with or without encephalopathy, within 40 days of marrow reinfusion. Evidence of metastatic liver disease was the only pretransplant characteristic predictive for VOD (P = .0002). Sex, age, histology, hepatitis B serology, and elevated liver function tests were not predictive. No individual preparative agent had a significant effect on the development of VOD. However, a single 2-hour infusion of carmustine (BCNU) (greater than or equal to 450 mg/m2) led to an increased incidence of VOD when compared with the same dose administered in a fractionated schedule (P = .0258) when given with two other chemotherapeutic agents. Seven of eight autopsy specimens confirmed the clinical diagnosis of VOD. The four patients in whom clinical VOD resolved had lower median peak bilirubins (7.3 v 15.9 mg/dL), lower median peak creatinines (2.1 v 4.1 mg/dL), and relatively quick engraftment of neutrophils (mean, 18.7 days). One of the four patients in whom VOD resolved had other grade 4 (life-threatening) toxicities in contrast to eight of eight who succumbed. In summary, VOD is an uncommon complication in autotransplantation of solid tumors and lymphomas. Our data suggest caution in selecting patients with known metastatic liver disease and consideration of a fractionated BCNU schedule especially in combination with other alkylating agents. .A Ayash LJ; Hunt M; Antman K; Nadler L; Wheeler C; Takvorian T; Elias A; Antin JH; Greenough T; Eder JP. .I 275855 .U 91011523 .S J Clin Oncol 9101; 8(10):1707-14 .M Actuarial Analysis; Adolescence; Adult; Antineoplastic Agents, Combined/AE; Bone Marrow Transplantation/*; Child; Child, Preschool; Evaluation Studies; Female; Graft Survival; Human; Leukemia, Nonlymphocytic, Acute/ET/MO/*SU; Leukemia, Radiation-Induced/ET/MO/SU; Lymphocyte Depletion; Male; Middle Age; Myelodysplastic Syndromes/ET/MO/*SU; Myelofibrosis/CO; Radiation Injuries/ET/MO/SU; Radiotherapy/AE; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Survival Rate; T-Lymphocytes. .T Bone marrow transplantation for myelodysplasia and secondary acute nonlymphoblastic leukemia. .P JOURNAL ARTICLE. .W Twenty-three patients with primary myelodysplasia (MDS) or secondary myelodysplasia/acute nonlymphocytic leukemia (MDS/ANLL) were treated with allogeneic or syngeneic bone marrow transplantation (BMT). Only one patient was in a chemotherapy-induced hematologic remission. Graft-versus-host disease prophylaxis included methotrexate, methotrexate plus cyclosporine, cyclosporine, or T-cell depletion using one of two anti-CD5 monoclonal antibodies. For patients with primary MDS, the median age was 19 years (range, 11 to 41 years) and the actuarial disease-free survival was 56% +/- 21% (median follow-up, 2 years; range, 0.8 to 5 years). There were three graft failures (two with autologous recovery) and two early deaths. Outcome appeared to be related to French-American-British (FAB) classification. For patients with secondary MDS/ANLL, the median age was 28 years (range, 3 to 16 years) and the actuarial disease-free survival was 27% +/- 13% (median follow-up, 5 years; range, 2.5 to 8.5 years). There were no graft failures, two relapses, and four early deaths. The presence of marrow fibrosis per se did not predict for graft failure (P = .21); however, the use of T-cell depleted marrow in patients with marrow fibrosis resulted in graft failure in three of five individuals. Our results suggest that in patients with primary MDS or secondary MDS/ANLL, BMT should be considered early in the course of the disease, and that attempts at inducing a remission prior to BMT appeared to be unnecessary. In MDS patients with marrow fibrosis, T-cell depletion should be avoided. .A Longmore G; Guinan EC; Weinstein HJ; Gelber RD; Rappeport JM; Antin JH. .I 275856 .U 91011524 .S J Clin Oncol 9101; 8(10):1715-20 .M Aged; Antineoplastic Agents/*TU; Biopsy; Carotene/*TU; Drug Evaluation; Female; Human; Leukoplakia/*DT/PA; Male; Middle Age; Mouth/PA; Mouth Neoplasms/*DT/PA; Remission Induction; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Response of oral leukoplakia to beta-carotene. .P JOURNAL ARTICLE. .W Leukoplakia is associated with increased risk of oral cancer and is considered a premalignant lesion. Retinoids, particularly 13-cis retinoic acid, can frequently reverse leukoplakia. However, these drugs have considerable toxicity and are not suitable for large-scale use in the prevention of oral cancer. Beta-carotene is a naturally occurring, nontoxic carotenoid with biologic properties that suggest that it might be efficacious against oral leukoplakia. In 1986, we began a randomized study of 13-cis retinoic acid (1 mg/kg/d) versus beta-carotene (30 mg/d) in leukoplakia. However, owing to the marked differences in toxicity between the two compounds outlined in the consent form, 11 of the initial 16 eligible patients refused to participate unless they were "guaranteed" beta-carotene. Therefore, the study design was changed to a phase II trial of beta-carotene in which the compound was given daily for 3 months. Responding patients were continued for another 3 months of treatment. All lesions were examined histologically at entry. Responses were monitored by bidimensional measurements and photography done at entry, then monthly while on treatment and at study completion. Twenty-four evaluable patients were treated, and 17 had major responses (two complete, 15 partial), a response rate of 71% (95% confidence limits, 53% to 89%). There was no significant toxicity requiring drug discontinuation or dose reduction. These results indicate that beta-carotene has substantial activity in oral premalignancy. Because of its lack of toxicity, it is an excellent candidate for a preventive agent for oral cancer. .A Garewal HS; Meyskens FL Jr; Killen D; Reeves D; Kiersch TA; Elletson H; Strosberg A; King D; Steinbronn K. .I 275857 .U 91011525 .S J Clin Oncol 9101; 8(10):1721-7 .M Adult; Aged; Aged, 80 and over; Antiemetics/*TU; Antineoplastic Agents, Combined/*AE; Breast Neoplasms/DT; Cyclophosphamide/AD/*AE; Double-Blind Method; Female; Human; Imidazoles/*TU; Male; Middle Age; Nausea/CI/*PC; Receptors, Serotonin/*AI; Support, Non-U.S. Gov't; Vomiting/CI/*PC. .T Antagonism of serotonin S3 receptors with ondansetron prevents nausea and emesis induced by cyclophosphamide-containing chemotherapy regimens [see comments] .P CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL. .W The control of nausea and emesis in cancer patients receiving chemotherapy poses a significant management problem. In this randomized, double-blind, placebo-controlled study, we evaluated the effect of serotonin S3 receptor blockade with ondansetron (GR 38032F) on the prevention of nausea and vomiting induced by cyclophosphamide-containing chemotherapy. Cyclophosphamide was given in doses of 500 to 600 mg/m2 and ondansetron as three intravenous (IV) doses of 0.15 mg/kg. Most patients had breast cancer. Cyclophosphamide was given in combination with doxorubicin (65% of patients) or with fluorouracil (85% of patients: 50% with Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH] and 35% with methotrexate). All placebo-treated patients experienced vomiting, whereas 70% of patients treated with ondansetron did not vomit (P = .008). Median nausea scores were 8 mm on ondansetron and 65 mm on placebo (P less than .001). Seventy percent of patients treated with ondansetron retained their normal appetite, compared with 10% of placebo patients. Adverse events occurred in six placebo patients and one ondansetron patient. Diarrhea and headache were the most common events, both occurring more frequently in the placebo group. There were no extrapyramidal reactions, and the only significant biochemical change occurred in a placebo-treated patient. These results suggest that serotonin S3 receptor antagonists represent a novel, effective, and safe mode of therapy for nausea and emesis induced by cyclophosphamide-containing chemotherapies. In addition, our observations are compatible with the view that serotonin, acting on S3 receptors, mediates the nausea and emesis occurring after cyclophosphamide chemotherapy. .A Cubeddu LX; Hoffman IS; Fuenmayor NT; Finn AL. .I 275858 .U 91011526 .S J Clin Oncol 9101; 8(10):1728-38 .M Adolescence; Adult; Aged; Agranulocytosis/CI; Antineoplastic Agents, Combined/*AD/AE/TU; Bone Marrow Transplantation/*; Cisplatin/AD/AE; Cyclophosphamide/AD/AE; Drug Administration Schedule; Drug Evaluation; Etoposide/AD/AE; Female; Human; Male; Middle Age; Neoplasms/*DT/MO; Remission Induction; Support, U.S. Gov't, P.H.S.; Survival Rate; Thrombocytopenia/CI. .T Phase I study of repeated cycles of high-dose cyclophosphamide, etoposide, and cisplatin administered without bone marrow transplantation [see comments] .P JOURNAL ARTICLE. .W Forty-two patients with advanced malignancy judged unlikely to respond to standard treatment received high-dose combination chemotherapy with cyclophosphamide, etoposide, and cisplatin in a phase I trial. Twenty-two of these patients who had at least a partial response (PR) to the first cycle of therapy received a second cycle, and eight patients received three or more cycles of therapy. Bone marrow replacement was not used. The maximum-tolerated doses (MTDs) were cyclophosphamide 2.5 g/m2 on days 1 and 2; etoposide 500 mg/m2 on days 1, 2, and 3; and cisplatin 50 mg/m2 on days 1, 2, and 3. Hematologic toxicity was not dose-limiting by study design. Recovery to an absolute granulocyte count above 100/microL occurred at a median of 9 days from onset (range, 3 to 23 days) at the MTD. Recovery was delayed after the third cycle. Only one patient on his third cycle failed to recover peripheral blood counts and died of sepsis an day 43. Hematologic toxicity was not dose-dependent. Nonhematologic toxicities included emesis, fatigue, alopecia, diarrhea, and anorexia and were generally well tolerated. The dose-limiting toxicities were fatal pulmonary or cardiac toxicities in five of nine patients treated at the highest dose level. Patients likely to do well can be selected by tumor type, response to prior therapy, and performance status. Nine of 36 assessable patients had a complete response (CR) and 13 a PR for a response rate of 61%. Five patients (12%) remain alive and free of disease at 15 to 32 months. Repeated cycles of dose-intensive combination therapy can produce long-term disease-free remissions in patients with refractory tumor types. The toxicity of the regimen is acceptable if patients are carefully selected. .A Neidhart JA; Kohler W; Stidley C; Mangalik A; Plauche A; Anderson T; Quenzer RW; Rinehart JJ. .I 275859 .U 91011527 .S J Clin Oncol 9101; 8(10):1739-53 .M Antineoplastic Agents/AE/*PK; Biological Transport; Biotransformation; Human; Models, Biological; Neoplasms/*DT/ME; Remission Induction; Support, Non-U.S. Gov't. .T Pharmacodynamics in cancer therapy. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W Our understanding of anticancer pharmacodynamics, and the relationships between pharmacologic measurements and clinical effects, has grown markedly in recent years due to advances in analytical and computational technology. Although methotrexate plasma levels have been empirically used to guide leucovorin dosing during high-dose methotrexate therapy, there has been no other standard use of therapeutic drug monitoring in oncology. More recently, investigators have attempted to titrate precisely the dose of antineoplastic agents based on previously derived models and real-time analysis of plasma drug or tissue concentrations. Studies have been completed or are in progress using hexamethylene bisacetamide, etoposide, teniposide, fluorouracil (FUra), and cytarabine (ara-C). Future studies will focus on optimal sampling strategies, analysis of intermediate biochemical end points, combination chemotherapy, modulation by colony-stimulating factors, and more sophisticated pharmacodynamic models. .A Ratain MJ; Schilsky RL; Conley BA; Egorin MJ. .I 275860 .U 91011529 .S J Clin Oncol 9101; 8(10):1767-8 .M Antibiotics/*TU; Bacterial Infections/*PC; Catheterization, Central Venous/*AE; Human; Interleukin-2/*AD; Neoplasms/TH; Recombinant Proteins/AD. .T Antibiotic prophylaxis to prevent catheter-related infections in recombinant interleukin-2-treated patients [letter; comment] .P COMMENT; LETTER. .A Orcese C; Borri A; Besana C. .I 275861 .U 91011530 .S J Clin Oncol 9101; 8(10):1768-9 .M Human; Multicenter Studies; Prognosis; Rhabdomyosarcoma/*DT; United States. .T Evidence of "stage shift" in IRS studies? [letter; comment] .P COMMENT; LETTER. .A Pritchard J. .I 275862 .U 91011603 .S J Neurosurg 9101; 73(5):651-60 .M Acquired Immunodeficiency Syndrome/*TM; Human; Risk Factors; Surgery/*. .T A surgeon's risk of AIDS. .P JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL. .W A probabilistic model is used to estimate the cumulative risk to surgeons from human immunodeficiency virus (HIV). Recent data suggest that the probability of infection following percutaneous inoculation is about 1 in 250 cases. Several studies suggest that the frequency of percutaneous injury in surgery is at least 1 in 40 cases, for some as high as 1 in 20 cases. Assuming that on the average a surgeon will perform 350 operations per year and will practice for 30 years, the cumulative risk of HIV infection will depend on the prevalence of HIV infection in the surgical population. For HIV prevalences of 1 in 100 to 1 in 10, the cumulative risk per surgeon ranges from 1 in 100 to 1 in 5, respectively. Based on these risk estimates, it is crucial to decrease the frequency of percutaneous injury. The case is made for substantial improvements in barrier protection and modification of surgical technique. .A Schiff SJ. .I 275863 .U 91011604 .S J Neurosurg 9101; 73(5):661-7 .M Adolescence; Adult; Case Report; Child; Child, Preschool; Human; Hypothalamic Neoplasms/PA/RA/*SU; Infant; Magnetic Resonance Imaging; Prognosis; Tomography, X-Ray Computed. .T Surgical management of exophytic chiasmatic-hypothalamic tumors of childhood. .P JOURNAL ARTICLE. .W Sixteen children underwent 18 operations for radical resection of chiasmatic-hypothalamic tumors. The clinical presentation correlated with age: infants under 1 year of age presented with macrocephaly, failure to thrive, and severe visual failure; children aged 1 to 5 years predominantly had precocious puberty with mild visual deficits; and older children (greater than 5 years old) had slowly progressive loss of vision. All three infants had biologically aggressive tumors in spite of low-grade histology, and died from progressive tumor growth. Eleven of the 13 children aged 1 year or over are alive and well, without clinical or radiographic evidence of disease progression, 4 months to 4 1/2 years following surgery. Six of these patients, with a follow-up period of 10 months to 4 1/2 years (mean 27 months), have had no adjuvant therapy following radical surgical resection. The authors conclude that: 1) radical surgical resection of chiasmatic-hypothalamic tumors can be performed with minimal morbidity; 2) radical resection may delay the time to disease progression in older children and postpone the need for irradiation; 3) resection of postirradiation recurrent tumors may provide neurological improvement and long-lasting clinical remission; and 4) chiasmatic-hypothalamic tumors of infancy are aggressive neoplasms that require multimodality therapy. .A Wisoff JH; Abbott R; Epstein F. .I 275864 .U 91011605 .S J Neurosurg 9101; 73(5):668-73 .M Adult; Aged; Case Report; Child; Child, Preschool; Female; Human; Infant; Male; Neurosurgery/*MT; Skull Neoplasms/*SU; Zygoma/*SU. .T Zygomatic approach to skull-base lesions. .P JOURNAL ARTICLE. .W A modification of the preauricular skull-base approach is described. After sectioning and downward displacement of the zygomatic arch, the coronoid process of the mandible is dissected and sectioned at its base. The temporal muscle, with its coronoid insertion, is then retracted upward. This approach provides direct and unobstructed access to the temporal and infratemporal fossae. Adequate vascularity of the temporal muscle is maintained. The exposure encompasses the internal carotid artery in the neck for vascular control. Extensive reconstruction is eliminated. The described technique was used in seven patients with lesions of the skull base. There was no operative mortality, and morbidity consisted of temporary restriction of mandibular opening in two patients. .A al-Mefty O; Anand VK. .I 275865 .U 91011606 .S J Neurosurg 9101; 73(5):674-83 .M Adenoma/PA/SE/*SU; Adult; Case Report; Female; Human; Hyperthyroidism/ET; Magnetic Resonance Imaging; Male; Middle Age; Pituitary Neoplasms/PA/SE/*SU; Thyrotropin/BL/*SE. .T Surgical treatment of thyrotropin-secreting pituitary adenomas. .P JOURNAL ARTICLE. .W Thyrotropin-secreting pituitary adenomas have been diagnosed more frequently as radiographic techniques and biochemical assays have improved; however, they remain uncommon and are unfamiliar to most neurosurgeons. This report concerns eight patients with hyperthyroidism, inappropriately elevated levels of serum thyrotropin and alpha-subunit, and radiographic evidence of pituitary tumor. All underwent surgery and had pathological confirmation of a thyrotropin-secreting adenoma, and most had been subjected to prior ablation of the thyroid gland. Only one tumor was a microadenoma; the others ranged in size from 1.4 to 12 cm, and invasion of parasellar structures was common. Thyrotropin, triiodothyronine, thyroxine, and alpha-subunit were measured preoperatively and at intervals postoperatively. Coexistent hormonal abnormalities (which occurred in all patients) included acromegaly and hyperprolactinemia and were also monitored. All four patients who had tumors less than 2 cm in diameter remain alive. Complete extirpation of tumor in these patients produced rapid correction of all hormonal abnormalities and resolution of clinical hyperthyroidism. The other four patients had larger invasive tumors: two died soon after surgery, one died of disseminated tumor 8 years after presentation, and one remains alive with residual tumor. Tumors secreting thyroid-stimulating hormone are less easily cured by surgery than are other types of pituitary adenoma because of the large size and invasive features that many attain during the delay to diagnosis; medical therapy can subdue the tumor but not cure it. The experience with these patients establishes the importance of early diagnosis and surgical excision for successful treatment, and demonstrates the utility of modern diagnostic techniques for finding these lesions. As occurs in Nelson's syndrome after adrenalectomy for Cushing's disease, ablation of the target organ may allow the tumor to convert to a more clinically malignant form which is resistant to cure. .A McCutcheon IE; Weintraub BD; Oldfield EH. .I 275866 .U 91011607 .S J Neurosurg 9101; 73(5):684-7 .M Adolescence; Brain Injuries/CO/*PP; Child; Child Behavior/PH; Child, Preschool; Cognition/PH; Follow-Up Studies; Handicapped; Human; Motor Activity/PH; Prognosis; Seizures/PP; Social Problems; Speech Disorders/PP; Time Factors. .T Long-term follow-up review of 31 children with severe closed head trauma. .P JOURNAL ARTICLE. .W Thirty-one children aged 3 to 15 years were followed for 5 to 11 years after suffering severe closed head trauma which caused coma for 1 week or more (median duration of coma 3 weeks). One patient remained in a persistent vegetative state until his death 9 years later. The other 30 recovered consciousness and were discharged. All suffered diminution of their abilities, and 24 of them had major permanent disability. The most common motor disabilities were pure spastic hemiparesis (seven cases), basal ganglia syndromes (four cases), ataxia (three cases), and a combination of hemiparesis and ataxia (five cases). Of the 30 patients, 26 regained independent ambulation, seven were epileptic, and 14 were dysarthric in various degrees. Only 10 had the cognitive ability to profit from the normal educational system, and none had attempted postsecondary education. Social problems were common. The worst outcomes were associated with intracranial bleeding and/or brain contusion seen on computerized tomography (CT) scans at the acute stage; the best were associated with normal CT scans. The degree of residual disability in these children seems no less than that of adults with trauma of similar severity. .A Costeff H; Groswasser Z; Goldstein R. .I 275867 .U 91011608 .S J Neurosurg 9101; 73(5):688-98 .M Anoxia/ET; Brain Injuries/CO/MO/*RA; Cerebral Hemorrhage/ET; Human; Hypotension/ET; Intracranial Pressure; Predictive Value of Tests; Prospective Studies; Risk Factors; Subarachnoid Space/BS; Support, U.S. Gov't, P.H.S.; Tomography, X-Ray Computed/*. .T Initial CT findings in 753 patients with severe head injury. A report from the NIH Traumatic Coma Data Bank. .P CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY. .W In this prospective multicenter study, the authors have examined data derived from the initial computerized tomography (CT) scans of 753 patients with severe head injury. When the CT findings were related to abnormal intracranial pressure and to death, the most important characteristics of the scans were: midline shift: compression or obliteration of the mesencephalic cisterns: and the presence of subarachnoid blood. Diffuse hemispheric swelling was also found to be associated with an early episode of either hypoxia or hypotension. .A Eisenberg HM; Gary HE Jr; Aldrich EF; Saydjari C; Turner B; Foulkes MA; Jane JA; Marmarou A; Marshall LF; Young HF. .I 275868 .U 91011609 .S J Neurosurg 9101; 73(5):699-709 .M Adolescence; Adult; Brain Injuries/*PP; Female; Follow-Up Studies; Glasgow Coma Scale; Human; Male; Neuropsychological Tests/*; Prognosis; Support, U.S. Gov't, P.H.S.. .T Neurobehavioral outcome 1 year after severe head injury. Experience of the Traumatic Coma Data Bank. .P JOURNAL ARTICLE. .W The outcome 1 year after they had sustained a severe head injury was investigated in patients who were admitted to the neurosurgery service at one of four centers participating in the Traumatic Coma Data Bank (TCDB). Of 300 eligible survivors, the quality of recovery 1 year after injury was assessed by at least the Glasgow Outcome Scale (GOS) in 263 patients (87%), whereas complete neuropsychological assessment was performed in 127 (42%) of the eligible survivors. The capacity of the patients to undergo neuropsychological testing 1 year after injury was a criterion of recovery as reflected by a significant relationship to neurological indices of acute injury and the GOS score at the time of hospital discharge. The neurobehavioral data at 1 year after injury were generally comparable across the four samples of patients and characterized by impairment of memory and slowed information processing. In contrast, language and visuospatial ability recovered to within the normal range. The lowest postresuscitation Glasgow Coma Scale (GCS) score and pupillary reactivity were predictive of the 1-year GOS score and neuropsychological performance. The lowest GCS score was especially predictive of neuropsychological performance 1 year postinjury in patients who had at least one nonreactive pupil following resuscitation. Notwithstanding limitations related to the scope of the TCDB and attrition in follow-up material, the results indicate a characteristic pattern of neurobehavioral recovery from severe head injury and encourage the use of neurobehavioral outcome measurements in clinical trials to evaluate interventions for head-injured patients. .A Levin HS; Gary HE Jr; Eisenberg HM; Ruff RM; Barth JT; Kreutzer J; High WM Jr; Portman S; Foulkes MA; Jane JA; et al. .I 275869 .U 91011610 .S J Neurosurg 9101; 73(5):710-4 .M Brain Neoplasms/*GE/PA; Case Report; Chromosomes, Human, Pair 22/*; Female; Human; Immunoenzyme Techniques; Infant; Karyotyping; Male; Monosomy/*; Rhabdomyosarcoma/*GE/PA; Support, U.S. Gov't, P.H.S.; Teratoma/*GE/PA. .T Monosomy 22 in rhabdoid or atypical tumors of the brain. .P JOURNAL ARTICLE. .W Cytogenetic studies of three rare childhood brain tumors were performed. Two children presented with pure rhabdoid tumors. The third child had a tumor composed of a mixture of rhabdoid elements with neuroepithelial, epithelial, and mesenchymal tissue - an atypical teratoid tumor. All three tumors demonstrated monosomy 22 as the only cytogenetic abnormality. The cytogenetic findings suggest that loss of a gene or genes on chromosome 22 may be involved in the initiation or progression of these malignant tumors. Further studies on additional fresh tumor specimens are warranted; however, it is possible that cytogenetic studies may be used as an additional means of diagnosing rhabdoid or atypical teratoid tumors of the brain. .A Biegel JA; Rorke LB; Packer RJ; Emanuel BS. .I 275870 .U 91011611 .S J Neurosurg 9101; 73(5):715-9 .M Adolescence; Adult; Brain Neoplasms/*DI/RA/UL; Diagnosis, Differential; Human; Immunohistochemistry; Male; Meningeal Neoplasms/*DI; Meningioma/*DI; Microscopy, Electron; Neurilemmoma/*DI/RA/UL; Tomography, X-Ray Computed. .T Meningiomas mimicking cerebral schwannoma. .P JOURNAL ARTICLE. .W A brain tumor with histological features reminiscent of schwannoma with underlying meningioangiomatosis was subjected to electron microscopic and immunohistochemical analysis, which confirmed the neoplasm as a meningioma. This prompted reexamination of a similar tumor, described in a previous publication as a cerebral schwannoma, with identical immunohistochemical techniques. The results obtained favored alteration of this diagnosis to that of meningioma. This experience has led the authors to recommend the use of immunohistochemistry techniques when evaluating unusual intracranial neoplasms. .A Louw D; Sutherland G; Halliday W; Kaufmann J. .I 275871 .U 91011612 .S J Neurosurg 9101; 73(5):720-4 .M Acquired Immunodeficiency Syndrome/CO/*PA/RA; Adult; Biopsy; Brain Diseases/*DI/ET/PA/RA; Diagnosis, Differential; Human; Leukoencephalopathy, Progressive Multifocal/DI/ET; Lymphoma/DI/ET; Magnetic Resonance Imaging/*; Male; Middle Age; Retrospective Studies; Tomography, X-Ray Computed/*; Toxoplasmosis/DI/ET. .T Use of CT and MR imaging to distinguish intracranial lesions and to define the need for biopsy in AIDS patients [see comments] .P JOURNAL ARTICLE. .W To explore the potential usefulness of imaging studies in the diagnosis of focal central nervous system (CNS) lesions associated with acquired immunodeficiency syndrome (AIDS), the authors retrospectively examined the radiographic studies of 149 AIDS patients who presented with signs and symptoms of the three most common focal CNS lesions. Of these patients, 74 (50%) had Toxoplasma abscesses, 45 (30%) had primary CNS lymphoma, and 30 patients (20%) had progressive multifocal leukoencephalopathy (PML). Magnetic resonance (MR) imaging was more sensitive than computerized tomography (CT) in detecting lesions, especially in cases of PML. Whereas CT was unable to distinguish mass lesions caused by toxoplasmosis from those caused by lymphoma, 71% of the solitary lesions seen on MR images were lymphomas. These results indicate that empirical treatment for toxoplasmosis, the most common initial treatment for AIDS patients with neurological symptoms stemming from mass lesions, is not likely to be successful for patients with solitary lesions on MR images. Rather, early biopsy is advisable. If the presence of lymphoma is confirmed, the rapid initiation of treatment can allow prolonged high-quality survival. .A Ciricillo SF; Rosenblum ML. .I 275872 .U 91011614 .S J Neurosurg 9101; 73(5):731-5 .M Adenoma/*GE/PA/UL; DNA, Neoplasm/AN; Female; Human; Microscopy, Electron; Pituitary Neoplasms/*GE/PA/UL; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; X Chromosome. .T Clonal origin of pituitary adenomas. .P JOURNAL ARTICLE. .W Benign pituitary adenomas are among the most common neurosurgical tumors and account for a diversity of clinical syndromes due to their hormone content and release. To determine whether these tumors arise from a single cell or multiple cells, the authors studied X chromosome inactivation in deoxyribonucleic acid (DNA) isolated from pituitary adenomas in women. Tumors of three different hormonal subtypes were examined. One tumor contained cells immunoreactive for prolactin and human growth hormone; one tumor contained foci immunoreactive for the beta-subunits of luteinizing hormone and follicle-stimulating hormone; and the third tumor had no immunoreactive prolactin, human growth hormone, beta-subunits of thyroid-stimulating hormone, luteinizing hormone, or follicle-stimulating hormone, or the alpha-subunit. Analysis of the DNA revealed that, in each of the three pituitary tumors, one X chromosome was active in all cells and one X chromosome was inactive, indicating that each of these tumors was monoclonal in origin. It is concluded that clinically evident pituitary tumors arise from a genetic mutation in a single cell. .A Jacoby LB; Hedley-Whyte ET; Pulaski K; Seizinger BR; Martuza RL. .I 275873 .U 91011615 .S J Neurosurg 9101; 73(5):736-42 .M Adult; Astrocytoma/*CH/PA; Brain Neoplasms/*CH/PA; Cell Division/DE; Dexamethasone/PD; Female; Glioma/*CH/PA; Human; Male; Middle Age; Radioligand Assay; Receptors, Androgen/AN; Receptors, Estrogen/AN; Receptors, Glucocorticoid/AN; Receptors, Progesterone/AN; Receptors, Steroid/*AN; Support, Non-U.S. Gov't; Testosterone/PD; Tumor Cells, Cultured. .T Characteristics and biological role of steroid hormone receptors in neuroepithelial tumors [see comments] .P JOURNAL ARTICLE. .W Tissue samples from 57 patients with neuroepithelial tumors (25 glioblastomas, 18 anaplastic astrocytomas, and 14 astrocytomas) were analyzed in order to evaluate the presence of estrogen, progesterone, glucocorticoid, and androgen receptors. Glucocorticoid- and androgen-specific binding proteins were present in 38.6% and 21.6% of the cases, respectively. Only a few tumors showed estrogen or progesterone receptors. A correlation was found between grade of anaplasia, patient's sex and age, and presence of glucocorticoid and androgen receptors. The biological role of these two receptors was investigated in 10 primary cell cultures derived from neuroepithelial tumors. For this purpose, dexamethasone and testosterone were added to culture medium at different concentrations (from 50 to 0.016 micrograms/ml). A significant stimulation of the cell growth was observed in four of five glucocorticoid receptor-positive cultures when dexamethasone in doses ranging from 2 to 0.016 microgram/ml was added to the culture. No modulation of the growth was observed in glucocorticoid receptor-negative cultures at the same doses. Higher dexamethasone doses induced a significant decrease of the growth index independently from the glucocorticoid receptor status. All of the cultures tested for testosterone activity were negative for androgen receptors. This hormone induced an inhibition of the growth index at doses ranging from 50 to 0.4 micrograms/ml. The data suggest that neuroepithelial tumors contain specific glucocorticoid and androgen binding proteins. Glucocorticoid receptors modulate the growth of cultured neuroepithelial tumors in the presence of different concentrations of dexamethasone. .A Paoletti P; Butti G; Zibera C; Scerrati M; Gibelli N; Roselli R; Magrassi L; Sica G; Rossi G; Robustelli della Cuna G. .I 275874 .U 91011616 .S J Neurosurg 9101; 73(5):743-9 .M Adult; Female; Human; Immunoenzyme Techniques; Immunohistochemistry; Kinetics; Male; Meningeal Neoplasms/*CH/DT/PA; Meningioma/*CH/DT/PA; Middle Age; Neoplasms, Hormone-Dependent/*CH/DT/PA; Nucleic Acid Hybridization; Oligonucleotide Probes; Prospective Studies; Radioligand Assay; Receptors, Estrogen/*AN/GE; Receptors, Progesterone/*AN; RNA, Messenger/AN; Support, Non-U.S. Gov't; Tumor Markers, Biological. .T Hormonal dependency of cerebral meningiomas. Part 1: Female sex steroid receptors and their significance as specific markers for adjuvant medical therapy. .P JOURNAL ARTICLE. .W Female sex steroid receptors were examined in 50 human cerebral meningiomas. For estrogen receptors, high-affinity binding sites (dissociation constant (Kd): 0.05 to 0.2 nM) were found in the cytosolic fraction with a capacity of less than 4 fmol/mg protein in 10 meningiomas using a dextran-coated charcoal (DCC) assay. In the same cytosolic fraction, the solid-phase enzyme immunoassay revealed only one cytosol with a positive colorimetric reaction equal to 5 fmol/mg protein. However, in the nuclear compartment, none of the tumors stained positively for estrogen receptors with immunohistochemical techniques. In addition, the most convincing evidence for the absence of estrogen receptors was obtained by in situ hybridization using an oligonucleotide probe complementary to a fraction of the human receptor messenger ribonucleic acid (mRNA). In none of the 50 meningiomas was the expression of estrogen mRNA coding for the estrogen receptor detected. For progesterone receptors, high-affinity binding sites (Kd: 0.3 to 2.6 nM) were found in 49 of the 50 tumors using a DCC assay. In the same cytosols, solid-phase enzyme immunoassay revealed that each tumor was positive for progesterone receptors. However, in the nuclear compartment, only five tumors had partially positive staining for progesterone receptors with immunohistochemical techniques. Within the confines of this study, it is concluded that: 1) the estrogen receptor is generally absent in meningioma tissue, and 2) the progesterone receptor is mainly absent in the nuclear compartment, leading to the conclusion that the cytosolic progesterone receptor may be an inactive form. This study suggests that female sex steroid receptors are not primarily involved in the proliferative rate of cerebral meningiomas and that they are of no current significance as markers for adjuvant medical therapy of most meningiomas. .A Scherell UM; Adams EF; Fahlbusch R; Greb R; Jirikowski G; Prior R; Ramalho-Ortigao FJ. .I 275875 .U 91011617 .S J Neurosurg 9101; 73(5):750-5 .M Bromocriptine/*PD; Cell Division/DE; DNA Polymerases/AN; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor-Urogastrone/*PD; Estradiol/PD; Human; Meningeal Neoplasms/*CH/PA; Meningioma/*CH/PA; Neoplasms, Hormone-Dependent/*CH/PA; Progestational Hormones/PD; Radioimmunoassay; Steroids/*PD; Support, Non-U.S. Gov't; Tumor Cells, Cultured/DE/PA. .T Hormonal dependency of cerebral meningiomas. Part 2: In vitro effect of steroids, bromocriptine, and epidermal growth factor on growth of meningiomas. .P JOURNAL ARTICLE. .W Cell culture and biochemical techniques have been employed to examine the effects of steroids, bromocriptine, and epidermal growth factor (EGF) on the growth and proliferative potential of meningiomas. In cell culture, the growth of meningiomas was not altered by progestogens, antiprogestogens, or 17beta-estradiol. The progestogen, norethisterone, had no effect on the uptake by meningiomas cell cultures of 3H-thymidine. Furthermore, cytosolic deoxyribonucleic acid (DNA) polymerase activity of meningiomas did not correlate with the progesterone receptor status of the same tumors. In contrast, the androgen antagonists, cyproterone acetate and 11-alpha-hydroxyprogesterone, and the dopamine agonist, bromocriptine, all inhibited the in vitro growth of meningioma cells. The growth of meningioma cell cultures was stimulated by EGF, and there was a positive correlation between the EGF content and DNA polymerase activity in meningioma cytosols. These results demonstrate that female sex steroids do not influence growth of meningiomas in vitro, whereas antiandrogens and bromocriptine have an antiproliferative effect. Consequently, bromocriptine and antiandrogens may have a role in the medical treatment of meningiomas. In addition, these results suggest that EGF may be involved in the genesis and/or progression of meningiomas. .A Adams EF; Schrell UM; Fahlbusch R; Thierauf P. .I 275876 .U 91011618 .S J Neurosurg 9101; 73(5):756-9 .M Animal; Carotid Arteries; Cerebral Angiography; Cerebrovascular Disorders/*CI; Dogs; Embolization, Therapeutic; Injections, Intra-Arterial; Methacrylates/*AE. .T Intracarotid hydroxyethyl methacrylate solution causing stroke in dogs. .P JOURNAL ARTICLE. .W Hydroxyethyl methacrylate (HEMA) has been advocated as a polymerizing solution with which to prevent deflation of detachable balloons in interventional neuroradiology. It is pertinent to know if unpolymerized HEMA would have untoward effects if accidentally released into the carotid artery by balloon rupture or deflation. Seven mongrel dogs underwent transfemoral catheterization of the common carotid artery and subsequent injection of HEMA solution in volumes of 1 cc in five dogs, 2 cc in one, and 4 cc in one. Angiography performed at the time of injection revealed evidence of intravascular thrombosis as well as possible spasm. Three surviving animals were sacrificed at 48 hours; the brains were fixed and examined histopathologically. One brain was normal and one was autolyzed and could not be examined. Five of the seven animals had histopathologically documented cerebral infarctions of varying size. No foreign substance was seen within the blood vessels to suggest intravascular polymerization. The animals injected with 2 or 4 cc HEMA solution did not survive 48 hours. Literature review reveals little documentation of the toxicology of intravascular HEMA. With its increasing popularity as a compound for polymerization in detachable balloons introduced into the brain, further investigations are warranted to understand the physical properties of the compound and potential risks of its use. .A Purdy P; White CL 3d; Batjer H; Brewer K; Hodges K; Samson D. .I 275877 .U 91011620 .S J Neurosurg 9101; 73(5):768-73 .M Arteriovenous Malformations/*CO/SU; Case Report; Child; Chylothorax/CO/SU; Female; Human; Lymphatic Diseases/*CO/SU; Spinal Cord/*BS. .T Spinal cord arteriovenous malformation with an associated lymphatic anomaly. Case report. .P JOURNAL ARTICLE. .W Spinal cord arteriovenous malformations (AVM's), like other vascular anomalies of the central nervous system, can be associated with similar vascular lesions of the skin and viscera. A 7-year-old girl, who presented with rapidly progressing paraplegia, was found to have a spinal cord AVM, cutaneous angioma, and a chylous malformation of the lymphatic system. She had previously undergone treatment for a posterior thoracic cutaneous angioma. At surgery, upon incision of the paravertebral muscle fascia, viscous pale fluid was encountered emanating from a foramen in the thoracic lamina. The spinal AVM was resected in spite of concern that the abnormality represented spinal osteomyelitis. Postoperatively, there was full return of function in the lower extremities, along with recurrent episodes of chylothorax, which slowly came under control with dietary manipulation. A review of the anatomy of the thoracic duct and nontraumatic causes of chylothorax is presented, and the association of cutaneous and central angiomas is discussed. Finally, the treatment of chylothorax is delineated. .A Kraus GE; Bucholz RD; Weber TR. .I 275878 .U 91011621 .S J Neurosurg 9101; 73(5):774-6 .M Adult; Case Report; Catheters, Indwelling/*; Female; Human; Injections, Intraventricular/*IS; Methotrexate/AD; Parkinson Disease/*ET. .T Hemiparkinsonism as a complication of an Ommaya reservoir. Case report. .P JOURNAL ARTICLE. .W The authors describe the case of a 28-year-old woman who developed the following symptoms in her right hand: a lasting resting tremor, transient focal rigidity, and paresthesia. These deficits occurred following treatment with intrathecal methotrexate via an Ommaya reservoir which was placed too deeply, resulting in trauma to the contralateral mesencephalon. .A Cheshire WP; Ehle AL. .I 275879 .U 91011622 .S J Neurosurg 9101; 73(5):777-81 .M Brain Neoplasms/*DI/PA/RA; Case Report; Cerebral Ventricles/*PA; Cerebral Ventriculography; Child; Human; Magnetic Resonance Imaging; Male; Neurilemmoma/*DI/PA/RA; Tomography, X-Ray Computed. .T Fourth ventricular schwannoma. Case report. .P JOURNAL ARTICLE. .W A schwannoma arising from the dorsum of the pontomedullary junction and presenting as an exophytic mass in the fourth ventricle is described. A ventricular schwannoma has not previously been reported in the literature. The presenting clinical and radiographic features and the pathology of this tumor are summarized, and an explanation is sought for its unusual location. .A Redekop G; Elisevich K; Gilbert J. .I 275880 .U 91011623 .S J Neurosurg 9101; 73(5):782-4 .M Adult; Brachial Plexus/PA/RA/*SU; Case Report; Female; Human; Myxoma/PA/RA/*SU; Nervous System Neoplasms/PA/RA/*SU; Tomography, X-Ray Computed. .T Myxomatous cyst of the brachial plexus. Case report. .P JOURNAL ARTICLE. .W The case of a myxomatous cyst of the brachial plexus is presented. The clinical course is reported, and the frequency of the lesion, diagnostic workup, histopathology, and surgical therapy are discussed. .A Arnold PM; Oldershaw JB; McDonald LW; Langer BG. .I 275881 .U 91011624 .S J Neurosurg 9101; 73(5):785-7 .M Calcinosis/*ET/PA/SU; Case Report; Human; Intervertebral Disk Displacement/PA/SU; Laminectomy/*/MT; Lumbar Vertebrae/PA/SU; Male; Meningocele/*ET/PA/SU; Middle Age; Postoperative Complications/*. .T Postlaminectomy ossified extradural pseudocyst. Case report. .P JOURNAL ARTICLE. .W A large ossified spurious meningocele accompanied by recurrent lumbar disc herniation occurred 7 years after posterior intervention for laminectomy and discectomy in a 53-year-old man. The cyst wall, histologically composed of mature bone tissue, was sparsely covered with connective tissue and lined with fibrocyte- or fibroblast-like cells on the inside. The ossified pseudocyst was presumed to have originated from a minute defect in the dura mater which occurred at the time of the first operation. .A Tsuji H; Handa N; Handa O; Tajima G; Mori K. .I 275882 .U 91011625 .S J Neurosurg 9101; 73(5):788-91 .M Adult; Case Report; Cysts/PA/*SU; Human; Male; Spinal Cord Diseases/PA/*SU. .T Intradural epithelial cyst at the craniovertebral junction. Case report. .P JOURNAL ARTICLE. .W A case of an intradural epithelial cyst at the craniovertebral junction is reported in a 37-year-old man. The classification of these rare lesions is discussed. .A Breeze RE; Nichols P; Segal H; Apuzzo ML. .I 275883 .U 91011626 .S J Neurosurg 9101; 73(5):792-7 .M Brain Mapping/*; Epilepsy, Temporal Lobe/*PP; Human; Image Processing, Computer-Assisted/*; Stereotaxic Techniques/*; Tomography, Emission-Computed. .T Stereotactic investigation of limbic epilepsy using a multimodal image analysis system. Technical note. .P JOURNAL ARTICLE. .W A methodology has been developed for stereotactic investigation of limbic epilepsy using an image-analysis system that simultaneously displays different structural and functional images of the brain. The validity and accuracy of this system were established with phantom studies. Surgical planning and electrode implantation are guided by stereotactic magnetic resonance imaging, digital subtraction angiography, and position emission tomography. This methodology provides the spatiotemporal relationship of cerebral structure and function necessary to identify seizure onset and propagation in human limbic system epilepsy. .A Levesque MF; Zhang JX; Wilson CL; Behnke EJ; Harper RM; Lufkin RB; Engel J Jr; Crandall PH. .I 275884 .U 91011627 .S J Neurosurg 9101; 73(5):798-800 .M Bone Wires/*; Cervical Vertebrae/*SU; Human; Joint Instability/*SU; Orthopedic Fixation Devices/*; Spine/*SU. .T A simple technique of posterior wiring in traumatic instability of the mid to lower cervical spine. Technical note. .P JOURNAL ARTICLE. .W Wiring without bone fusion in the treatment of traumatic cervical instability is an uncommon procedure. The authors describe a semirigid wiring technique for stabilizing the acute injured movement segment in the mid and lower cervical spine. Results are briefly discussed. .A Brandt L; Nielsen CF; Saveland H; Wingstrand H. .I 275885 .U 91011628 .S J Neurosurg 9101; 73(5):804-5 .M Aged; Balloon Dilatation/*MT; Human; Middle Age; Trigeminal Neuralgia/*TH. .T Percutaneous microcompression for trigeminal neuralgia [letter; comment] .P COMMENT; LETTER. .A Zanusso M; Colombo F. .I 275886 .U 91011629 .S J Neurosurg 9101; 73(5):805-7 .M Animal; Blood-Brain Barrier/*DE; Dogs; Osmolar Concentration/*. .T Hyperosmotic blood-brain barrier disruption [letter; comment] .P COMMENT; LETTER. .A Gumerlock MK. .I 275887 .U 91011630 .S J Neurosurg 9101; 73(5):807-8 .M Human; Spinal Cord Compression/*SU; Spinal Fusion/*MT. .T One-stage posterolateral decompression and fusion [letter; comment] .P COMMENT; LETTER. .A Chiou SM. .I 275888 .U 91011631 .S J Neurosurg 9101; 73(5):808 .M Brain Injuries/*CO; Hematoma, Subdural/*ET; Human. .T "Spat-apoplexie" [letter; comment] .P COMMENT; LETTER. .A Parkinson D. .I 275889 .U 91011632 .S J Nucl Med 9101; 31(10):15A-21A .M Europe; Human; Nuclear Medicine/*TD. .T Highlights of the 1990 EANM (European Association of Nuclear Medicine) Congress. .P JOURNAL ARTICLE. .I 275890 .U 91011634 .S J Nucl Med 9101; 31(10):1601-7 .M Adult; Aged; Cerebrovascular Disorders/ET/PX/*RI; Cognition Disorders/DI/ET; Female; Human; HIV Seropositivity/*CO/PX; Male; Memory Disorders/DI/ET; Tomography, Emission-Computed, Single-Photon/*; Xenon Radioisotopes/*DU. .T Disturbances in the cerebral perfusion of human immune deficiency virus-1 seropositive asymptomatic subjects: a quantitative tomography study of 18 cases. .P JOURNAL ARTICLE. .W Quantitative measurements of cerebral blood flow (CBF) by xenon-133 (133Xe) tomography, together with magnetic resonance imaging (MRI), electroencephalography (EEG), psychometric tests, and laboratory analyses were performed on 18 human immunodeficiency virus 1 (HIV-1) seropositive asymptomatic subjects. Abnormalities of cerebral perfusion were observed in 16 cases (88%). These abnormalities were particularly frequent in the frontal regions (77% of cases). MRI demonstrated leucoencephalopathy in only two cases. EEG showed only induced diffuse abnormalities in two cases. Psychometric tests showed restricted moderate disturbances in 55% of patients. These disturbances mostly concerned those sectors involved in cognitive functions and memorization. These results indicate that quantitative measurements of CBF by 133Xe-SPECT is capable of detecting abnormalities of cerebral perfusion at a very early stage (Phase II) of HIV-1 infection. These abnormalities are indications of disturbances resulting from unidentified metabolic or vascular lesions. This technique appears to be superior to MRI at this stage of the disease's development. It could provide objective information leading to earlier treatment, and prove useful in evaluating potential antiviral chemotherapy. .A Tran Dinh YR; Mamo H; Cervoni J; Caulin C; Saimot AC. .I 275891 .U 91011635 .S J Nucl Med 9101; 31(10):1608-16 .M Animal; Carbon Radioisotopes/DU; Coenzyme A/ME; Comparative Study; Fatty Acids/BL/DU/*PK; Heart/RI; Human; In Vitro; Iodine Radioisotopes/DU; Iodobenzenes/BL/DU/*PK; Kinetics; Male; Myocardium/*ME; Rats; Rats, Inbred Strains. .T Tracer kinetics of 15-(ortho-123/131I-phenyl)-pentadecanoic acid (oPPA) and 15-(para-123/131I-phenyl)-pentadecanoic acid (pPPA) in animals and man. .P JOURNAL ARTICLE. .W The human myocardium retains oPPA as opposed to pPPA. Therefore turnover of oPPA was compared with that of pPPA in rat hearts and in man, the latter by using substrates double-labeled with 123/131I and 14C. Moreover, substrate binding to coenzyme-A was tested in vitro. In rats, oPPA remained mainly in the pool of free fatty acids, as opposed to pPPA, which was metabolized by mitochondrial beta-oxidation. Binding to coenzyme-A at maximum was 62% for oPPA, 81% for pPPA and 90% for palmitic acid. In man, after i.v. and intracoronary injection of double-labeled oPPA, the two radionuclides reappeared together in venous blood and in coronary sinus respectively, in an unchanged ratio but at a significantly lower rate than with pPPA. It can be concluded that oPPA is bound to coenzyme-A and is retained in the cytosolic lipid pool, while pPPA is metabolized by mitochondrial beta-oxidation. A dual-tracer application of oPPA and pPPA has the potential of being a specific probe for the function of the carnitine shuttle. .A Kaiser KP; Geuting B; Grossmann K; Vester E; Losse B; Antar MA; Machulla HJ; Feinendegen LE. .I 275892 .U 91011636 .S J Nucl Med 9101; 31(10):1617-23 .M Adult; Aged; Comparative Study; Coronary Disease/PP/RA/*RI; Coronary Vessels/*RA; Female; Human; Male; Middle Age; Myocardial Contraction/*PH; Thallium Radioisotopes/AD/*DU; Time Factors. .T Significance of fill-in after thallium-201 reinjection following delayed imaging: comparison with regional wall motion and angiographic findings [see comments] .P JOURNAL ARTICLE. .W To identify reversible defects, reinjection of a small amount of thallium-201 (201Tl) following 3-hr delayed imaging was performed in 60 patients with coronary artery disease who had perfusion abnormalities on their post-exercise 201Tl images. Thallium-201 uptake was visually scored and judged as normal (Group 1), reversible defect (Group II), new fill-in after reinjection (Group IIIa) and no fill-in even after reinjection (Group IIIb). New fill-in after reinjection was observed in 27 segments of the 85 segments (32%), showing persistent defect on the stress and delayed images. The wall motion in Group IIIa was worse than Group II but better than Group IIIb. Group IIIa showed Q-wave on ECG more often (69%) than Group II (27%) (p less than 0.01), but less often than Group IIIb (85%) (p less than 0.05). These data indicate that the reinjection 201Tl imaging often identifies new fill-in in the areas of no redistribution on the delayed images and it may hold promise for assessing tissue viability which the conventional imaging may underestimate. .A Tamaki N; Ohtani H; Yonekura Y; Nohara R; Kambara H; Kawai C; Hirata K; Ban T; Konishi J. .I 275893 .U 91011637 .S J Nucl Med 9101; 31(10):1623-6 .M Coronary Disease/PA/*RI; Human; Myocardium/*PA; Thallium Radioisotopes/AD/*DU. .T Rest reinjection of thallium-201 after redistribution imaging: new questions, old solution [editorial; comment] .P COMMENT; EDITORIAL. .A Rocco TP. .I 275894 .U 91011638 .S J Nucl Med 9101; 31(10):1627-31 .M Follow-Up Studies; Human; Iodohippuric Acid/DU; Kidney Transplantation/*AE; Lymphocele/EP/ET/*RI; Retrospective Studies; Technetium Tc 99m Pentetate/DU. .T Lymphocele: the spectrum of scintigraphic findings in lymphoceles associated with renal transplant. .P JOURNAL ARTICLE. .W Lymphocele is a well recognized complication of renal transplant surgery. We performed a retrospective review of 305 renal transplant patients with over 2,500 scintigraphic exams to describe the pattern of activity on technetium-99m-DTPA blood flow and dynamic imaging, and iodine-131-OIH studies. Diagnostic criteria for a lymphocele were ultrasonic evidence of a perirenal fluid collection and analysis of that fluid that demonstrated BUN, creatinine, and electrolytes similar to the patient's plasma. Scintigraphic findings were attributed to a lymphocele if abnormalities were in the same area as the ultrasound fluid collection. Scintigraphic findings attributable to lymphocele resolved in all patients following surgical drainage or peritoneal window placement. Six of the 11 documented lymphoceles demonstrated a cold defect on initial dynamic images that "filled in" to equal background activity and another exceeded background. Three cases showed a rim of increased activity surrounding the lymphocele ("rim sign"). .A Fortenbery EJ; Blue PW; Van Nostrand D; Anderson JH. .I 275895 .U 91011639 .S J Nucl Med 9101; 31(10):1632-4 .M Adult; Citrates/DU; Dimercaptosuccinic Acid/*DU; Female; Fibroma/*RI; Gallium Radioisotopes/*DU; Human; Male; Neoplasm Recurrence, Local/RI; Organotechnetium Compounds/*DU. .T Scintigraphic evaluation of aggressive fibromatosis. .P JOURNAL ARTICLE. .W Despite its benign microscopic appearance, aggressive fibromatosis has potential to recur and infiltrate neighboring tissues. Therefore, it is necessary to determine the exact extent before therapy. In the present study, 11 cases of aggressive fibromatosis were examined scintigraphically using [99mTc(V)]dimercaptosuccinic acid (11 cases) and 67Ga-citrate (7 cases). Technetium-99m-(V)-dimercaptosuccinic acid demonstrated all lesions, while 67Ga-citrate detected 57% of the cases. .A Ohta H; Endo K; Konishi J; Iwasaki R; Kotoura Y; Yamamuro T; Kotoura H. .I 275896 .U 91011640 .S J Nucl Med 9101; 31(10):1635-40 .M Animal; Cysteamine/CH/CS/PK; Gallium Radioisotopes/*DU; Heart/*RI; Isotope Labeling; Macaca fascicularis; Male; Rats; Rats, Inbred Strains; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Tissue Distribution; Tomography, Emission-Computed. .T A new myocardial imaging agent: synthesis, characterization, and biodistribution of gallium-68-BAT-TECH [see comments] .P JOURNAL ARTICLE. .W In order to develop a new myocardial perfusion agent for positron emission tomography (PET), a new lipid-soluble gallium complex was evaluated. Synthesis, radiolabeling, characterization, and biodistribution of a unique gallium complex, [67Ga]BAT-TECH (bis-aminoethanethiol-tetraethyl-cyclohexyl), are described. The complex formation between Ga+3 and BAT-TECH ligand is simple, rapid, and of high yield (greater than or equal to 95%). This process is amenable to kit formulation. The complex has a net charge of +1 and a Ga/ligand ratio of 1:1. Biodistribution in rats shows high uptake in the heart as well as in the liver. When [68Ga] BAT-TECH was injected into a monkey, the heart and liver are clearly delineated by PET imaging, suggesting that this complex may be a possible tracer for myocardial perfusion imaging. .A Kung HF; Liu BL; Mankoff D; Kung MP; Billings JJ; Francesconi L; Alavi A. .I 275897 .U 91011641 .S J Nucl Med 9101; 31(10):1641-5 .M Animal; Brain/*RI; Heart/*RI; Human; Radionuclide Generators/*; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Tomography, Emission-Computed/*. .T The potential for generator-based PET perfusion tracers [editorial; comment] .P COMMENT; EDITORIAL. .A Green MA. .I 275898 .U 91011642 .S J Nucl Med 9101; 31(10):1646-53 .M Animal; Cell Line; Cell Line, Transformed; Cell Membrane/*PH; Chick Embryo; Fibroblasts/*ME; In Vitro; Membrane Potentials/*PH; Mice; Mitochondria/*PH; Nitriles/*PK; Organotechnetium Compounds/*PK; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.. .T Effect of mitochondrial and plasma membrane potentials on accumulation of hexakis (2-methoxyisobutylisonitrile) technetium(I) in cultured mouse fibroblasts. .P JOURNAL ARTICLE. .W Hexakis(2-methoxyisobutylisonitrile) technetium(I) (Tc-MIBI) is representative of a class of 99mTc-based lipophilic cationic myocardial perfusion imaging agents. To test the hypothesis that the mechanism of cellular uptake may involve distribution across biologic membranes in response to membrane potential, Tc-MIBI net uptake and retention were determined in cultured mouse BALB/c 3T3, NIH 3T3, and v-src transformed NIH 3T3 fibroblasts as well as in cultured chick embryo heart cells. Isovolumic depolarization of plasma membrane potentials with 130 mM K 20 mM Cl buffer decreased Tc-MIBI net cell uptake in all preparations. In BALB/c 3T3 cells, depolarizing mitochondrial membrane potential with valinomycin in high K buffer or with the protonophore CCCP inhibited net uptake and retention of Tc-MIBI while hyperpolarizing mitochondrial and plasma membrane potentials with the K+/H+ exchanger nigericin increased Tc-MIBI net uptake. These results indicated that net cellular uptake and retention of Tc-MIBI in fibroblasts were determined by both mitochondrial and plasma membrane potentials; the gamma-emitting properties of Tc-MIBI may therefore raise the possibility of monitoring membrane potential in vivo. .A Chiu ML; Kronauge JF; Piwnica-Worms D. .I 275899 .U 91011643 .S J Nucl Med 9101; 31(10):1654-8 .M Acetylglucosamine/*AA/DU/PK; Animal; Autoradiography; Fluorine Radioisotopes/*DU; Liver Neoplasms, Experimental/ME; Male; Mice; Mice, Inbred C3H; Neoplasms, Experimental/ME/*RI; Rabbits; Support, Non-U.S. Gov't; Tissue Distribution; Tomography, Emission-Computed. .T N-[18F]fluoroacetyl-D-glucosamine: a potential agent for cancer diagnosis [see comments] .P JOURNAL ARTICLE. .W Positron labeled substrates such as sugars, amino acids, and nucleosides have been investigated for the in-vivo evaluation of biochemical processes in cancerous tissue. Hexosamines are obligatory structural components of many biologically important macromolecules, including membrane glycoproteins and mucopolysaccharide. We evaluated a new synthesized pharmaceutical, N-[18F]fluoroacetyl-D-glucosamine (18F-FAG), which is a structural analog of N-acetyl-D-glucosamine. C3H/HeMsNRS mice bearing spontaneous hepatomas were used for the tissue distribution study. At 60 min after injection, high uptakes were found in tumor (5.16, mean value of %dose/g), liver (3.71), and kidney (3.27). The tumor uptake of 18F-FAG showed the highest value in all tissue. In the PET study, VX-2 carcinoma of the rabbit was clearly visualized. Our preliminary results suggest that 18F-FAG has potential as a new agent for tumor imaging. .A Fujiwara T; Kubota K; Sato T; Matsuzawa T; Tada M; Iwata R; Itoh M; Hatazawa J; Sato K; Fukuda H; et al. .I 275900 .U 91011644 .S J Nucl Med 9101; 31(10):1658-61 .M Comparative Study; Costs and Cost Analysis; Human; Magnetic Resonance Imaging/EC; Neoplasms/DI/RA/*RI; Tomography, Emission-Computed/EC; Tomography, X-Ray Computed/EC. .T The current and future use of tumor-localizing agents [editorial; comment] .P COMMENT; EDITORIAL. .A Davis M. .I 275901 .U 91011645 .S J Nucl Med 9101; 31(10):1662-8 .M Animal; Ethylenediamines/CH/*PK; Female; Iron Chelates/CH/PK; Rats; Rats, Inbred Strains; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Tissue Distribution. .T Investigation of physicochemical and in-vivo behavior of diastereomeric iron-59, gallium-68, and indium-111-EHPG trivalent metal complexes [published erratum appears in J Nucl Med 1991 Jan;32(1):15] .P JOURNAL ARTICLE. .W EHPG (N, N'-ethylenebis-[2-(o-hydroxyphenyl)glycine]) trivalent metal complexes show diagnostic potential both in radiopharmaceutical applications (gallium-68, indium-111) and as MRI contrast agents (iron). Although several publications report similar behavior of iron, gallium and indium complexes, we observe significant differences between EHPG complexes of these metals both in physicochemical and in vivo analyses. In addition, stereospecific behavior has been observed for the two diastereomers of EHPG when complexed with each metal. Complexes of Fe[59Fe], 68Ga, and 111In with meso, racemic, and unseparated EHPG have been evaluated. Relative lipophilicity has been measured with HPLC. Blood clearance and liver uptake have been correlated with pM values, stability constants and metal ion reduction potentials. .A Madsen SL; Bannochie CJ; Martell AE; Mathias CJ; Welch MJ. .I 275902 .U 91011646 .S J Nucl Med 9101; 31(10):1669-74 .M Adult; Bladder Neoplasms/PA/*RI; Case Report; Human; Iodine Radioisotopes/DU; Iodobenzenes/*DU; Male; Pheochromocytoma/PA/*RI; Prostatic Neoplasms/PA/RI. .T Perivesicle pheochromocytoma: the role of iodine-131-MIBG imaging [clinical conference] .P CLINICAL CONFERENCE; JOURNAL ARTICLE. .A Engelman K; Dweck E. .I 275903 .U 91011647 .S J Nucl Med 9101; 31(10):1675-81 .M Algorithms; Evaluation Studies; Female; Human; Image Processing, Computer-Assisted; Male; Support, Non-U.S. Gov't; Tomography, Emission-Computed/IS/*MT. .T Tomography using a rotating slant-hole collimator and a large number of projections [see comments] .P JOURNAL ARTICLE. .W A tomographic method using a limited-view angle has been evaluated. In studies using a gamma camera and a rotating 30-degree slant-hole (RSH) collimator, 64 projection images were registered. A special filtered backprojection technique was used for reconstruction of section images parallel to the collimator face. Resolution within such sections was 0.6 cm, 3 cm from the collimator face and 1.3 cm at 18 cm. Depth resolution was 2.2 cm at 3 cm and 5.1 cm at 18 cm. Spacing between section images was regular and geometric distortion negligible. Short-axis section images of a myocardium in vivo were qualitatively comparable or better than those obtained with single-photon emission computed tomography. Degradation in the posterior wall due to attenuation and scatter was less. Section images of the facial bones and a hip joint further demonstrated the tomographic capability of the method. .A Dale S; Bone D. .I 275904 .U 91011648 .S J Nucl Med 9101; 31(10):1682-8 .M Comparative Study; Heart/*RI; Human; Models, Structural; Support, Non-U.S. Gov't; Thallium Radioisotopes/*DU; Tomography, Emission-Computed/IS/*MT; Tomography, Emission-Computed, Single-Photon. .T Thallium-201 myocardial tomography with a rotating slant-hole collimator and a large number of projections [see comments] .P JOURNAL ARTICLE. .W Tomographic imaging of the myocardium was performed using a gamma camera and a 30-degree rotating slant-hole collimator to register 64 projections from a restricted-view angle. Section images were reconstructed with a two-dimensional filtered backprojection technique. Performance in terms of resolution, effects of misalignment, and three-dimensional activity distribution was evaluated in phantom studies. In a limited clinical study, ten consecutive patients were imaged both with single-photon emission computed tomography (SPECT) and the method described. In the new method, the camera was orientated in the 30 degrees left anterior oblique position with 15 degrees cranial tilt. Due to the short distance from the myocardium to the camera, resolution within reconstructed section images was high, the noise level was comparatively low, and the mean activity level in the posterior wall was significantly higher (p less than 0.005) than in SPECT. .A Dale S; Bone D. .I 275905 .U 91011649 .S J Nucl Med 9101; 31(10):1688-92 .M Algorithms; Image Processing, Computer-Assisted; Tomography, Emission-Computed/IS/*MT. .T Limited-angle tomography for the nineties [editorial; comment] .P COMMENT; EDITORIAL. .A Barrett HH. .I 275906 .U 91011650 .S J Nucl Med 9101; 31(10):1693-701 .M Human; Likelihood Functions; Mathematics; Models, Theoretical; Radionuclide Imaging/*SN; Support, U.S. Gov't, P.H.S.. .T Maximum-likelihood estimation: a mathematical model for quantitation in nuclear medicine. .P JOURNAL ARTICLE. .W In a stimulation study, we investigated the limitations of quantitation in nuclear medicine using a maximum-likelihood (ML) estimation model. We estimated activity, size, and position of a disk-shaped object on a circular, uniform background of unknown activity. The parameter estimates were unbiased, and their standard error was proportional to the square root of the total image counts. The estimates of object activity and size were strongly (negatively) correlated; the position estimates, however, were not correlated with estimates of any other parameters. This implies that a priori knowledge of object location does not improve precision. The minimal model of quantitation tasks should incorporate unknown object activity and size as well as unknown background activity. The ML estimation procedure was used to investigate the trade-off between resolution and sensitivity in gamma camera collimator design. The results implied that for complex tasks such as the multiparameter estimation task investigated here, optimum performance is achieved at a better resolution than that previously found optimal for detection of a well-specified object in a known background. .A Muller SP; Kijewski MF; Moore SC; Holman BL. .I 275907 .U 91011651 .S J Nucl Med 9101; 31(10):1702-9 .M Extracellular Space/ME; Gastric Mucosa/ME; Human; Kidney/ME; Pharmacokinetics; Radioactive Tracers/*; Technetium Tc 99m Pentetate/PK; Technetium Tc 99m Pertechnetate/PK; Thyroid Gland/ME. .T Temporal behavior of peripheral organ distribution volume in mammillary systems. I. A new tool for in vivo tracer kinetic analysis. .P JOURNAL ARTICLE. .W In complex mammillary compartmental systems, the kinetic solutions for central and peripheral compartments are sums of too many exponentials to be accurately analyzed without very sophisticated mathematical tools. Our data show the peripheral organ distribution volume (PODV) kinetics to exhibit systematic time behavior depending on its mode of relation with plasma: linear increase for irreversible transfer, uniexponential function growing toward as asymptotic value for reversible transfer. Statistical analysis of our kinetic data shows that no other significant information can be extracted at least inside the time and statistical noise limits of our investigation. After intravenous injection of a diffusible tracer, the total activity in any region of interest (ROI) in the body is the sum of various components and,